S
Seasonal rise in ACTH
Sedation
Sepsis Related Laminitis (SRL) (was SIRS - Systemic Inflammatory Response Syndrome)
SGLT-2 inhibitors (Canagliflozin, Ertugliflozin, Velagliflozin...)
Sheath - swelling and smegma as indicators of IR
Shoes
Sinusitis
Sole - necrosis and penetration
Somatostatin
Sphingolipids
Stevia/Stevioside
Stress
Sugar and starch
Support and advice
Supporting Limb Laminitis
Supraorbital hollows/fossae
Sedation
Sepsis Related Laminitis (SRL) (was SIRS - Systemic Inflammatory Response Syndrome)
SGLT-2 inhibitors (Canagliflozin, Ertugliflozin, Velagliflozin...)
Sheath - swelling and smegma as indicators of IR
Shoes
Sinusitis
Sole - necrosis and penetration
Somatostatin
Sphingolipids
Stevia/Stevioside
Stress
Sugar and starch
Support and advice
Supporting Limb Laminitis
Supraorbital hollows/fossae
Seasonal rise in ACTH
|
All horses (in the northern hemisphere) experience a seasonal rise in ACTH levels starting around 21 June, being most significant from August to October, peaking at the end of September/start of October, and finishing around 21 December. Horses with PPID have significantly higher ACTH levels than healthy horses, and their seasonal rise may last longer, particularly in older horses/as PPID advances.
When the seasonal rise in ACTH was first identified, a 2 tiered cut off for ACTH was suggested (see 2012 graph below), with Liphook Equine Hospital (LEH) using a cut off of 29 pg/ml from November to July, and 47 pg/ml from August to October (using Immulite CIA). However, since around 2016 LEH have been using weekly ACTH cut offs for diagnosing PPID, for increased accuracy. Horses that are developing PPID may show more obvious clinical signs of PPID during the seasonal rise, and any horse having unexplained laminitis, particularly for the first time, during or following the seasonal rise should be tested for PPID by testing ACTH (and insulin to assess insulin dysregulation and ideally glucose too). |
From "You've diagnosed PPID, now what" webinar by Andy Durham of Liphook Equine Hospital, August 2015
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The weekly ACTH cut offs used from around 2016.
From: Seasonal Changes in ACTH Secretion - Andy Durham, LEH |
There is likely to be a grey area either side of ACTH cut offs - diagnosing PPID from blood is currently not accurate as many factors affect ACTH (see Does a high ACTH result mean my horse has PPID?), and clinical signs must be taken into account alongside blood results.
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Many horses diagnosed with PPID need a higher dose of Pergolide during the seasonal rise, which can often be tapered down again from around December (with symptoms closely monitored), and increasing doses may be needed as the horse gets older. Some vets will suggest a trial of Pergolide for any horse with unexplained and unresolved autumn laminitis.
See Should I seasonally alter the dose of Prascend...? See the ECIR website for more information. Research |
The old 2-tiered ACTH cut offs (from 2012). Courtesy of Andy Durham at Liphook Equine Hospital
|
Equine Veterinary Journal August 2011
Circannual variation in plasma adrenocorticotropic hormone concentrations in the UK in normal horses and ponies, and those with pituitary pars intermedia dysfunction
Copas VEN, Durham AE
"Results: Upper limits for reference interval of plasma ACTH were 29 pg/ml between November and July and 47 pg/ml between August and October. Circannual variation in plasma ACTH occurred in both non-PPID and PPID horses with the highest ACTH concentrations found between August and October in both groups. The greatest difference between the 2 populations also occurred between August and October.
Conclusions: Plasma ACTH can be used for the diagnosis and monitoring of PPID throughout the year with the use of appropriate reference intervals. These findings demonstrate an increase in pituitary gland secretory activity during the late summer and autumn in both normal and PPID cases."
Journal of Veterinary Internal Medicine, 25: 872–881 (PubMed)
The Effect of Geographic Location, Breed, and Pituitary Dysfunction on Seasonal Adrenocorticotropin and α-Melanocyte-Stimulating Hormone Plasma Concentrations in Horses
McFarlane, D., Paradis, M., Zimmel, D., Sykes, B., Brorsen, B., Sanchez, A. and Vainio, K. (2011),
"RESULTS: The fall peak plasma α-MSH concentration occurred earlier in horses residing at more northern locations. Mean seasonal α-MSH concentrations were similar in all healthy groups at all locations, but in the fall, plasma ACTH concentrations were higher in horses living in more southern locations. Plasma ACTH but not α-MSH concentrations were higher in Morgan horses compared with light breed horses from the same location. Hormone concentrations of ponies did not differ from those of horses during either season. Concentrations of both hormones were high in the fall compared with the spring in horses with PPID.
CONCLUSIONS AND CLINICAL IMPORTANCE: These findings suggest geographic location of residence and breed may affect the onset, amplitude, or both of the seasonal peak of pars intermedia (PI) hormones and should be considered when performing diagnostic testing for PPID. Horses with PPID maintain seasonal regulation of PI hormone output."
J Vet Intern Med. 2011 May-Jun;25(3):579-85. doi: 10.1111/j.1939-1676.2011.0712.x. Epub 2011 Apr 1.
Seasonal changes in plasma adrenocorticotropic hormone and α-melanocyte-stimulating hormone in response to thyrotropin-releasing hormone in normal, aged horses.
Funk RA, Stewart AJ, Wooldridge AA, Kwessi E, Kemppainen RJ, Behrend EN, Zhong Q, Johnson AK
"Endogenous and TRH-stimulated ACTH and α-MSH concentrations were significantly different across months with higher concentrations in the summer and fall compared with February."
Vet J. 2010 Jul;185(1):58-61.
The use of adrenocorticotrophic hormone as a potential biomarker of pituitary pars intermedia dysfunction in horses.
Lee ZY, Zylstra R, Haritou SJ
J Vet Intern Med 2010;24:650–654
Seasonal Variation in Serum Concentrations of Selected Metabolic Hormones in Horses
Place NJ, McGowan CM, Lamb SV, Schanbacher BJ, McGowan T, Walsh DM
"ACTH values during August, September, and October were significantly higher than all other months. The lowest plasma ACTH was found in April, which was significantly lower than in June, August, September, October, and December. The greatest
proportion of horses having an ACTH concentration above the reference range (9–35 pg/mL) was in September for controls (4 of 7) and for EMS horses (7 of 8). Moreover, the EMS group had a substantial number of horses in August (4 of 7), in September (3 of 8), and in
October (3 of 9) with ACTH concentrations above the cutoff for Cushing’s disease (70 pg/mL), whereas no more than 2 of 7 control horses had such high ACTH concentrations in August and in October."
J Am Vet Med Assoc. 2009 Sep 15;235(6):715-22.
Evaluation of plasma ACTH, alpha-melanocyte-stimulating hormone, and insulin concentrations during various photoperiods in clinically normal horses and ponies and those with pituitary pars intermedia dysfunction.
Beech J, Boston RC, McFarlane D, Lindborg S
"Log ACTH concentration was increased during photoperiod 4 (6-7 Aug) through 8 (16-18 Oct), compared with photoperiod 1 (13 Feb-2 Mar) through 3 (19-22 Jun), in all groups. In photoperiod 3 (19-22 Jun) through 7 (26-28 Sep), log ACTH concentrations were higher in horses and ponies with PPID, compared with values for control horses and ponies.
J Vet Intern Med 2005;19:217–222
Variation in Plasma Adrenocorticotropic Hormone Concentration and Dexamethasone Suppression Test Results with Season, Age, and Sex in Healthy Ponies and Horses
Mark T. Donaldson, Sue M. McDonnell, Barbara J. Schanbacher, Stephen V. Lamb, Dianne McFarlane, and Jill Beech
"In summary, plasma ACTH concentration was markedly higher in September than in January and May. Clinically important seasonal differences in DST results were present. The positive correlations between age and plasma ACTH concentration and plasma cortisol concentration suggests deterioration in PA function with age."
McFarlane D, Donaldson MT, McConnell SM, Cribb AE
Effects of season and sample handling on measurement of plasma α-melanocyte-stimulating hormone concentrations in horses and ponies
AJVR, Vol 65, No. 11, November 2004 (Full)
Alpha-MSH was higher in September compared with January, March, April, June and November. Increased alpha-MSH has been found in Soay sheep in Scotland in late summer/autumn, at the same time as peaks in body weight, voluntary food intake and condition, suggesting that alpha-MSH or other POMC hormones may play a role in metabolic preparation for winter. The paper suggests that it is possible that horses have a similar seasonal increase in POMC hormones to prepare them for less readily available food during the winter.
Circannual variation in plasma adrenocorticotropic hormone concentrations in the UK in normal horses and ponies, and those with pituitary pars intermedia dysfunction
Copas VEN, Durham AE
"Results: Upper limits for reference interval of plasma ACTH were 29 pg/ml between November and July and 47 pg/ml between August and October. Circannual variation in plasma ACTH occurred in both non-PPID and PPID horses with the highest ACTH concentrations found between August and October in both groups. The greatest difference between the 2 populations also occurred between August and October.
Conclusions: Plasma ACTH can be used for the diagnosis and monitoring of PPID throughout the year with the use of appropriate reference intervals. These findings demonstrate an increase in pituitary gland secretory activity during the late summer and autumn in both normal and PPID cases."
Journal of Veterinary Internal Medicine, 25: 872–881 (PubMed)
The Effect of Geographic Location, Breed, and Pituitary Dysfunction on Seasonal Adrenocorticotropin and α-Melanocyte-Stimulating Hormone Plasma Concentrations in Horses
McFarlane, D., Paradis, M., Zimmel, D., Sykes, B., Brorsen, B., Sanchez, A. and Vainio, K. (2011),
"RESULTS: The fall peak plasma α-MSH concentration occurred earlier in horses residing at more northern locations. Mean seasonal α-MSH concentrations were similar in all healthy groups at all locations, but in the fall, plasma ACTH concentrations were higher in horses living in more southern locations. Plasma ACTH but not α-MSH concentrations were higher in Morgan horses compared with light breed horses from the same location. Hormone concentrations of ponies did not differ from those of horses during either season. Concentrations of both hormones were high in the fall compared with the spring in horses with PPID.
CONCLUSIONS AND CLINICAL IMPORTANCE: These findings suggest geographic location of residence and breed may affect the onset, amplitude, or both of the seasonal peak of pars intermedia (PI) hormones and should be considered when performing diagnostic testing for PPID. Horses with PPID maintain seasonal regulation of PI hormone output."
J Vet Intern Med. 2011 May-Jun;25(3):579-85. doi: 10.1111/j.1939-1676.2011.0712.x. Epub 2011 Apr 1.
Seasonal changes in plasma adrenocorticotropic hormone and α-melanocyte-stimulating hormone in response to thyrotropin-releasing hormone in normal, aged horses.
Funk RA, Stewart AJ, Wooldridge AA, Kwessi E, Kemppainen RJ, Behrend EN, Zhong Q, Johnson AK
"Endogenous and TRH-stimulated ACTH and α-MSH concentrations were significantly different across months with higher concentrations in the summer and fall compared with February."
Vet J. 2010 Jul;185(1):58-61.
The use of adrenocorticotrophic hormone as a potential biomarker of pituitary pars intermedia dysfunction in horses.
Lee ZY, Zylstra R, Haritou SJ
J Vet Intern Med 2010;24:650–654
Seasonal Variation in Serum Concentrations of Selected Metabolic Hormones in Horses
Place NJ, McGowan CM, Lamb SV, Schanbacher BJ, McGowan T, Walsh DM
"ACTH values during August, September, and October were significantly higher than all other months. The lowest plasma ACTH was found in April, which was significantly lower than in June, August, September, October, and December. The greatest
proportion of horses having an ACTH concentration above the reference range (9–35 pg/mL) was in September for controls (4 of 7) and for EMS horses (7 of 8). Moreover, the EMS group had a substantial number of horses in August (4 of 7), in September (3 of 8), and in
October (3 of 9) with ACTH concentrations above the cutoff for Cushing’s disease (70 pg/mL), whereas no more than 2 of 7 control horses had such high ACTH concentrations in August and in October."
J Am Vet Med Assoc. 2009 Sep 15;235(6):715-22.
Evaluation of plasma ACTH, alpha-melanocyte-stimulating hormone, and insulin concentrations during various photoperiods in clinically normal horses and ponies and those with pituitary pars intermedia dysfunction.
Beech J, Boston RC, McFarlane D, Lindborg S
"Log ACTH concentration was increased during photoperiod 4 (6-7 Aug) through 8 (16-18 Oct), compared with photoperiod 1 (13 Feb-2 Mar) through 3 (19-22 Jun), in all groups. In photoperiod 3 (19-22 Jun) through 7 (26-28 Sep), log ACTH concentrations were higher in horses and ponies with PPID, compared with values for control horses and ponies.
J Vet Intern Med 2005;19:217–222
Variation in Plasma Adrenocorticotropic Hormone Concentration and Dexamethasone Suppression Test Results with Season, Age, and Sex in Healthy Ponies and Horses
Mark T. Donaldson, Sue M. McDonnell, Barbara J. Schanbacher, Stephen V. Lamb, Dianne McFarlane, and Jill Beech
"In summary, plasma ACTH concentration was markedly higher in September than in January and May. Clinically important seasonal differences in DST results were present. The positive correlations between age and plasma ACTH concentration and plasma cortisol concentration suggests deterioration in PA function with age."
McFarlane D, Donaldson MT, McConnell SM, Cribb AE
Effects of season and sample handling on measurement of plasma α-melanocyte-stimulating hormone concentrations in horses and ponies
AJVR, Vol 65, No. 11, November 2004 (Full)
Alpha-MSH was higher in September compared with January, March, April, June and November. Increased alpha-MSH has been found in Soay sheep in Scotland in late summer/autumn, at the same time as peaks in body weight, voluntary food intake and condition, suggesting that alpha-MSH or other POMC hormones may play a role in metabolic preparation for winter. The paper suggests that it is possible that horses have a similar seasonal increase in POMC hormones to prepare them for less readily available food during the winter.
Sedation - effects on endocrine blood testing
From 2021 Equine Endocrinology Group Recommendations for the Diagnosis and Treatment of PPID, Table 4 Other considerations for managing horses with PPID.
Kritchevsky JE, Muir GS, Leschke DHZ, Hodgson JK, Hess EK, Bertin FR
Blood glucose and insulin concentrations after alpha-2-agonists administration in horses with and without insulin dysregulation
J Vet Intern Med. 2020 Mar;34(2):902-908. doi: 10.1111/jvim.15747. Epub 2020 Feb 26
Keywords: detomidine, endocrinology, equine, metabolism, pancreas, xylazine
Blood glucose and insulin concentrations after alpha-2-agonists administration in horses with and without insulin dysregulation
J Vet Intern Med. 2020 Mar;34(2):902-908. doi: 10.1111/jvim.15747. Epub 2020 Feb 26
Keywords: detomidine, endocrinology, equine, metabolism, pancreas, xylazine
Sepsis Related Laminitis (SRL)
Three forms of laminitis are currently recognized: endocrinopathic laminitis (EL) (due to insulin dysregulation, probably around 90% of all laminitis),
Sepsis Related Laminitis (SRL) where the horse is already very ill, and Supporting Limb Laminitis (SLL) where the horse is already very lame.
Sepsis related laminitis (SRL) occurs secondary to a serious primary illness involving the systemic inflammatory response syndrome (SIRS)/sepsis, usually involving bacterial infection and systemic inflammation, e.g. colitis, pleuropneumonia, enteritis, septic metritis (retained placenta), carbohydrate overload (getting into the feed room).
The horse will usually have a raised temperature, increased heart rate and abnormal white blood cell counts and will often have diarrhoea, anorexia and/or be depressed. Sepsis-related laminitis usually has a rapid onset and is often more severe than endocrinopathic laminitis, with catastrophic failure of the lamellae often leading to significant sinking, penetration of the sole by P3 and loss of blood perfusion.
Treatment involves aggressive treatment of the primary illness, cryoptherapy (icing the feet), anti-inflammatory therapy, trimming the feet to realign rotation and reduce weight-bearing on the walls, and supporting the feet through the solar structures.
Note that until it was discovered that insulin dysregulation causes most laminitis, around 2007, if a horse had laminitis it was thought to be sepsis related laminitis, and most experimentally induced laminitis has been sepsis related laminitis. This has probably led to laminitis being feared more than it should, as although sepsis related laminitis is often very serious, it is also reasonably rare (outside of hospitalized horses), and most cases of laminitis are the generally less severe and more easily treated and rehabilitated endocrinopathic laminitis (which it is quite common for ponies to have for months, even years, before anyone realizes they have got laminitis).
Elliott J, Bailey SR.
A review ofcellular and molecular mechanisms in endocrinopathic, sepsis-related and supporting limb equine laminitis.
Equine Vet J. Published online 27 February 2023. doi: 10.1111/evj.13933. PMID: 36847165. Open Access.
Keywords: basal epithelial cell stress; horse; insulin dysregulation; laminitis pathogenesis; signalling pathways.
Luethy D, Feldman R, Stefanovski D, Aitken MR.
Risk factors for laminitis and nonsurvival in acute colitis: Retrospective study of 85 hospitalized horses (2011-2019).
J Vet Intern Med. 2021 Jul;35(4):2019-2025. doi: 10.1111/jvim.16147. Epub 2021 May 3. PMID: 33938584; PMCID: PMC8295695.
Sheats MK
A Comparative Review of Equine SIRS, Sepsis, and Neutrophils
Front Vet Sci. 2019;6:69. Published 2019 Mar 12. doi:10.3389/fvets.2019.00069
Bertin FR, Ruffin-Taylor D, Stewart AJ
Insulin dysregulation in horses with systemic inflammatory response syndrome
J Vet Intern Med. July-August 2018;32(4):1420-1427. Published online 10 May 2018. doi: 10.1111/jvim.15138
Preventing and Treating Sepsis-Related Laminitis - www.thehorse.com January 2018
Laskoski LM, Locatelli-Dittrich R, Sousa RS, Brum JS, Cristo TG, Montiani-Ferreira F, Beltrame OC, Valadão CAA
Laminar lesions in horses with systemic oxidative stress, committed by experimentally induced or naturally occurring gastrointestinal disorders
Pesquisa Veterinária Brasileira August 2016, 36(8), 694-700. https://doi.org/10.1590/S0100-736X2016000800003
Tadros EM, Frank N, Horohov DW
Inflammatory Cytokine Gene Expression in Blood During the Development of Oligofructose-Induced Laminitis in Horses
Journal of Equine Veterinary Science Article in press published online 04 March 2013
Horses given 10 g/kg BW oligofructose had whole blood increases in interleukin-1beta, interleukin-8 and interleukin-10 8 hours after administration, clinical signs of laminitis were seen between 12 and 24 hours, therefore the research concluded that leukocyte cytokine expression increases as systemic inflammation develops and this is seen before lameness. Measures should be taken to control the systemic inflammatory response in order to lower the risk of laminitis developing in horses with SIRS. Tumor necrosis factor-alpha did not change. Increases in interleukin-6 were also seen but not until 16 and 20 hours after administration of OF.
Katz LM, Bailey SR
A review of recent advances and current hypotheses on the pathogenesis of acute laminitis
Equine Veterinary Journal Volume 44, Issue 6, pages 752–761, November 2012
Belknap, J. K. and Black, S. J.
Sepsis-related laminitis
Equine Veterinary Journal, 44: 738–740 (2012)
Read about TB colt Paynter's fight with SIRS laminitis following colitis on Fran Jurga's hoof blog
Laskoski LM, Locatelli-Dittrich R, Valadão CA, Deconto I, Gonçalves KA, Montiani-Ferreira F, Brum JS, de Brito HF, de Sousa RS
Systemic leukopenia, evaluation of laminar leukocyte infiltration and laminar lesions in horses with naturally occurring colic syndrome
Res Vet Sci. 2015 Aug;101:15-21. doi: 10.1016/j.rvsc.2015.05.014. Epub 2015 Jun 5
Tadros EM, Frank N, Newkirk KM, Donnell RL, Horohov DW
Effects of a “two-hit” model of organ damage on the systemic inflammatory response and development of laminitis in horses
Veterinary Immunology and Immunopathology In press available online 6 September 2012
Lipopolysaccharide and oligofructose administration increased temperature, heart rate and respiratory rate.
Equine Vet J. 2011 Dec 30. doi: 10.1111/j.2042-3306.2011.00531.x. [Epub ahead of print] (PubMed)
Hindlimb laminar inflammatory response is similar to that present in forelimbs after carbohydrate overload in horses.
Leise BS, Faleiros RR, Watts M, Johnson PJ, Black SJ, Belknap JK. Source Department of Veterinary Clinical Sciences, College of Veterinary Medicine,
"A significant proinflammatory response is known to occur in the forelimb lamina after carbohydrate administration." Horses were given 17.6 g of starch/kg bodyweight (8.8 kg/500 kg horse) via nasogastric tube and anaesthetised either after developing a temperature > 38.9'C or at the onset of Obel grade 1 lameness.
"Results: Increases in laminar MAC387-positive leucocytes and laminar messenger ribonucleic acid (mRNA) concentrations (P<0.05) for interleukin-1β, interleukin-6, cyclo-oxygenase-2, chemokine (C-X-C motif)ligand (CXCL)1 and CXCL8 were present in both fore- and hindlimb laminae from horses with OG1 lameness. Both CXCL1 and CXCL8 were also increased in forelimb and hindlimb laminae in the DEV horses. Conclusions: Administration of carbohydrate resulted in a similar inflammatory response in the hindlimb laminae to that previously reported for the forelimb laminae. These findings suggest that other factors, such as weightbearing, may play an important role in the development of laminitis after a systemic inflammatory condition develops. Potential relevance: Evidence of inflammation in the hindlimb laminae suggests that the hindfeet should be addressed in the septic horse at risk for laminitis; however, laminitis is often less severe in the hindlimbs due to other factors, such as weightbearing and hoof angle."
Equine Vet J. 2011 Jan;43(1):54-61. doi: 10.1111/j.2042-3306.2010.00122.x.
Laminar inflammatory gene expression in the carbohydrate overload model of equine laminitis.
Leise BS, Faleiros RR, Watts M, Johnson PJ, Black SJ, Belknap JK
AAEP 2009
Overview of What We Know About the Pathophysiology of Laminitis
Susan C. Eades
Lee Ann Fugler PhD dissertation 2009
Matrix Metalloproteinases in the Equine Systemic Inflammatory Response: Implications for Equine Laminitis
Paynter Watch: How Is Post-Colitis Laminitis Different from Common Chronic Laminitis? - www.hoofblog.com
Rowe JB, Lees MJ, Pethick DW
Prevention of Acidosis and Laminitis Associated with Grain Feeding in Horses
J. Nutr. 124: 2742S-2744S, 1994
Sepsis Related Laminitis (SRL) where the horse is already very ill, and Supporting Limb Laminitis (SLL) where the horse is already very lame.
Sepsis related laminitis (SRL) occurs secondary to a serious primary illness involving the systemic inflammatory response syndrome (SIRS)/sepsis, usually involving bacterial infection and systemic inflammation, e.g. colitis, pleuropneumonia, enteritis, septic metritis (retained placenta), carbohydrate overload (getting into the feed room).
The horse will usually have a raised temperature, increased heart rate and abnormal white blood cell counts and will often have diarrhoea, anorexia and/or be depressed. Sepsis-related laminitis usually has a rapid onset and is often more severe than endocrinopathic laminitis, with catastrophic failure of the lamellae often leading to significant sinking, penetration of the sole by P3 and loss of blood perfusion.
Treatment involves aggressive treatment of the primary illness, cryoptherapy (icing the feet), anti-inflammatory therapy, trimming the feet to realign rotation and reduce weight-bearing on the walls, and supporting the feet through the solar structures.
Note that until it was discovered that insulin dysregulation causes most laminitis, around 2007, if a horse had laminitis it was thought to be sepsis related laminitis, and most experimentally induced laminitis has been sepsis related laminitis. This has probably led to laminitis being feared more than it should, as although sepsis related laminitis is often very serious, it is also reasonably rare (outside of hospitalized horses), and most cases of laminitis are the generally less severe and more easily treated and rehabilitated endocrinopathic laminitis (which it is quite common for ponies to have for months, even years, before anyone realizes they have got laminitis).
Elliott J, Bailey SR.
A review ofcellular and molecular mechanisms in endocrinopathic, sepsis-related and supporting limb equine laminitis.
Equine Vet J. Published online 27 February 2023. doi: 10.1111/evj.13933. PMID: 36847165. Open Access.
Keywords: basal epithelial cell stress; horse; insulin dysregulation; laminitis pathogenesis; signalling pathways.
Luethy D, Feldman R, Stefanovski D, Aitken MR.
Risk factors for laminitis and nonsurvival in acute colitis: Retrospective study of 85 hospitalized horses (2011-2019).
J Vet Intern Med. 2021 Jul;35(4):2019-2025. doi: 10.1111/jvim.16147. Epub 2021 May 3. PMID: 33938584; PMCID: PMC8295695.
Sheats MK
A Comparative Review of Equine SIRS, Sepsis, and Neutrophils
Front Vet Sci. 2019;6:69. Published 2019 Mar 12. doi:10.3389/fvets.2019.00069
Bertin FR, Ruffin-Taylor D, Stewart AJ
Insulin dysregulation in horses with systemic inflammatory response syndrome
J Vet Intern Med. July-August 2018;32(4):1420-1427. Published online 10 May 2018. doi: 10.1111/jvim.15138
Preventing and Treating Sepsis-Related Laminitis - www.thehorse.com January 2018
Laskoski LM, Locatelli-Dittrich R, Sousa RS, Brum JS, Cristo TG, Montiani-Ferreira F, Beltrame OC, Valadão CAA
Laminar lesions in horses with systemic oxidative stress, committed by experimentally induced or naturally occurring gastrointestinal disorders
Pesquisa Veterinária Brasileira August 2016, 36(8), 694-700. https://doi.org/10.1590/S0100-736X2016000800003
Tadros EM, Frank N, Horohov DW
Inflammatory Cytokine Gene Expression in Blood During the Development of Oligofructose-Induced Laminitis in Horses
Journal of Equine Veterinary Science Article in press published online 04 March 2013
Horses given 10 g/kg BW oligofructose had whole blood increases in interleukin-1beta, interleukin-8 and interleukin-10 8 hours after administration, clinical signs of laminitis were seen between 12 and 24 hours, therefore the research concluded that leukocyte cytokine expression increases as systemic inflammation develops and this is seen before lameness. Measures should be taken to control the systemic inflammatory response in order to lower the risk of laminitis developing in horses with SIRS. Tumor necrosis factor-alpha did not change. Increases in interleukin-6 were also seen but not until 16 and 20 hours after administration of OF.
Katz LM, Bailey SR
A review of recent advances and current hypotheses on the pathogenesis of acute laminitis
Equine Veterinary Journal Volume 44, Issue 6, pages 752–761, November 2012
Belknap, J. K. and Black, S. J.
Sepsis-related laminitis
Equine Veterinary Journal, 44: 738–740 (2012)
Read about TB colt Paynter's fight with SIRS laminitis following colitis on Fran Jurga's hoof blog
Laskoski LM, Locatelli-Dittrich R, Valadão CA, Deconto I, Gonçalves KA, Montiani-Ferreira F, Brum JS, de Brito HF, de Sousa RS
Systemic leukopenia, evaluation of laminar leukocyte infiltration and laminar lesions in horses with naturally occurring colic syndrome
Res Vet Sci. 2015 Aug;101:15-21. doi: 10.1016/j.rvsc.2015.05.014. Epub 2015 Jun 5
Tadros EM, Frank N, Newkirk KM, Donnell RL, Horohov DW
Effects of a “two-hit” model of organ damage on the systemic inflammatory response and development of laminitis in horses
Veterinary Immunology and Immunopathology In press available online 6 September 2012
Lipopolysaccharide and oligofructose administration increased temperature, heart rate and respiratory rate.
Equine Vet J. 2011 Dec 30. doi: 10.1111/j.2042-3306.2011.00531.x. [Epub ahead of print] (PubMed)
Hindlimb laminar inflammatory response is similar to that present in forelimbs after carbohydrate overload in horses.
Leise BS, Faleiros RR, Watts M, Johnson PJ, Black SJ, Belknap JK. Source Department of Veterinary Clinical Sciences, College of Veterinary Medicine,
"A significant proinflammatory response is known to occur in the forelimb lamina after carbohydrate administration." Horses were given 17.6 g of starch/kg bodyweight (8.8 kg/500 kg horse) via nasogastric tube and anaesthetised either after developing a temperature > 38.9'C or at the onset of Obel grade 1 lameness.
"Results: Increases in laminar MAC387-positive leucocytes and laminar messenger ribonucleic acid (mRNA) concentrations (P<0.05) for interleukin-1β, interleukin-6, cyclo-oxygenase-2, chemokine (C-X-C motif)ligand (CXCL)1 and CXCL8 were present in both fore- and hindlimb laminae from horses with OG1 lameness. Both CXCL1 and CXCL8 were also increased in forelimb and hindlimb laminae in the DEV horses. Conclusions: Administration of carbohydrate resulted in a similar inflammatory response in the hindlimb laminae to that previously reported for the forelimb laminae. These findings suggest that other factors, such as weightbearing, may play an important role in the development of laminitis after a systemic inflammatory condition develops. Potential relevance: Evidence of inflammation in the hindlimb laminae suggests that the hindfeet should be addressed in the septic horse at risk for laminitis; however, laminitis is often less severe in the hindlimbs due to other factors, such as weightbearing and hoof angle."
Equine Vet J. 2011 Jan;43(1):54-61. doi: 10.1111/j.2042-3306.2010.00122.x.
Laminar inflammatory gene expression in the carbohydrate overload model of equine laminitis.
Leise BS, Faleiros RR, Watts M, Johnson PJ, Black SJ, Belknap JK
AAEP 2009
Overview of What We Know About the Pathophysiology of Laminitis
Susan C. Eades
Lee Ann Fugler PhD dissertation 2009
Matrix Metalloproteinases in the Equine Systemic Inflammatory Response: Implications for Equine Laminitis
Paynter Watch: How Is Post-Colitis Laminitis Different from Common Chronic Laminitis? - www.hoofblog.com
Rowe JB, Lees MJ, Pethick DW
Prevention of Acidosis and Laminitis Associated with Grain Feeding in Horses
J. Nutr. 124: 2742S-2744S, 1994
|
Is pasture associated laminitis SAL or endocrine?
It is now recognized that pasture associated laminitis (PAL) is endocrine laminitis, caused by insulin levels being too high (insulin dysregulation/hyperinsulinaemia/insulin resistance): "Endocrinopathic laminitis primarily comprises equine metabolic syndrome (EMS, including pasture-associated laminitis) and pituitary pars intermedia dysfunction (PPID)..." - Equine Laminitis James Belknap 2017 Ch. 47 Belknap and Durham. Can eating grass cause SAL laminitis? Although sepsis associated laminitis has been caused experimentally by giving horses large amounts of short-chain fructan (inulin) in one dose by naso-gastric tube, it seems very unlikely that grass or fructan ingestion would cause SAL for several reasons: |
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- Even with very high fructan levels in grass, it would be almost impossible for a horse to naturally ingest the amount of fructan used to experimentally induce laminitis over a whole day - and even if it could, the effect of the fructan would almost certainly be very different. It is almost certainly the sudden change caused by administering a large amount of fructan that caused the experimental laminitis, not the fructan itself.
- The fructan used to induce experimental laminitis is a short-chain fructan, different to the fructan found in grass. It is likely that a short-chain fructan would ferment more rapidly than the long-chain fructans found in grass, thereby causing a more significant effect.
- Horses that develop laminitis that seems to be related to eating grass do not show the raised temperature, abnormal white blood cell counts and diarrhoea seen in horses with SAL.
- If horses developed SAL from eating grass, then all horses (of different breeds, ages and fitness) in the same field would be likely to develop laminitis at the same time - this doesn't happen.
Glunk EC
Effect of Restricted Grazing on Dietary Energy Intake, Dry Matter Intake Rates, and Fecal pH
MSc thesis 2012
Faecal pH was not affected by length of grazing (3, 6, 9 or 24 hours had mean faecal pH of 7.23, 7.30, 7.32 and 7.61 respectively).
SGLT-2 inhibitors - Canagliflozin, Ertugliflozin, Velagliflozin....
Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are used to treat diabetes mellitus in humans. They work by reducing the reabsorption of glucose in the kidneys (by blocking SGLT-2 reabsorption of glucose), causing glucose to be excreted from the body in the urine. This lowers blood glucose concentrations and therefore insulin concentrations are reduced. No SGLT-2 medicines are licensed for horses as at 2022. Consequently there is no official reporting for side effects in horses, and interactions with other medications may not be known SGLT-2 medicines currently being given to horses with insulin dysregulation include Canagliflozin (sold under the trade name Invokana), Ertugliflozin and Velagliflozin.
Please read this imporant information from the Equine Endocrinology Group before using SGLT-2 inhibitors e.g. Ertugliflozin, Invokana/Canagliflozin, Velagliflozin:
Under the heading Medical Therapy on page 14 of Recommendations for the Diagnosis and Treatment of Equine Metabolic Syndrome (EMS) 2022 Equine Endocrinology Group
"Sodium-glucose co-transporter 2 (SGLT2) inhibitors
Indications: Used when horses are affected by laminitis and severe ID are not responding to other measures, and the owner has sufficient resources to pay for an expensive medical treatment. Drugs in this group act by inhibiting the reuptake of glucose from the glomerular filtrate, with more glucose lost in the urine as a result. Blood glucose concentrations decrease in response to treatment, and the amount of insulin needed to maintain euglycemia decreases proportionally. In initial studies in ponies, blood insulin concentrations significantly decreased over time when the SGLT2 inhibitor velagliflozin was administered orally at a dose of 0.3 mg/kg every 24 hours. Velagliflozin is not available for purchase at present, but two drugs in the same group, canagliflozin (0.5 mg/kg, PO, q24h) and ertugliflozin (0.05 mg/kg POq24h), are available. They are labeled for the treatment of diabetes mellitus in humans. Both drugs have been used with some success in a small number of horses with severe ID, but they are expensive in some countries and are reserved for horses with laminitis and severe ID that do not respond to recommended management changes. Smaller equids may be treated at a more reasonable cost. Lipid mobilization is stimulated in many horses treated with SGLT2 inhibitors, and hypertriglyceridemia might develop as a consequence. Thus, horses with marked hypertriglyceridemia should not be treated with these drugs.
Practice Tip: Although the SGLT2 inhibitors are promising drugs, it is essential that TG concentrations be monitored when treatment is initiated because individual horses might develop severe hypertriglyceridemia (>1,000 mg/dL; 26 mmol/L). Collect blood at 7 and 14 days, and then every 1-3 months thereafter. A risk/benefit assessment is needed if hypertriglyceridemia develops, and treatment decisions should be based on the severity of laminitis. Moderate hypertriglyceridemia (>100 mg/dL; 2.6 mmol/L) may affect the liver and other organs, and gamma glutamyl transferase (GGT) concentrations should be monitored if this problem develops. Management practices to address hyperinsulinemia must also be instituted at the same time, with the goal of discontinuing SGLT2 inhibitor treatment once the horse’s condition stabilizes. The EEG does not condone prescribing drugs for the treatment of ID without making appropriate management changes. The outcomes and health consequences of long-term treatment with SGLT2 inhibitors have not yet been evaluated in horses so these drugs should only be used in the short term (three months) until more research has been performed."
Ertugliflozin appears to be the most commonly prescribed SGLT-2 inhibitor for horses in the UK as at 2022.
See BEVA Client Information Leaflet Ertugliflozin published 10 February 2022
Research
Sundra T, Kelty E, Rendle D
Preliminary observations on the use of ertugliflozin in the management of hyperinsulinaemia and laminitis in 51 horses: A case series
BEVA Equine Veterinary Education published online 17 November 2022. https://doi.org/10.1111/eve.13738. Open Access.
See also EVE Video Abstract No. 27 Preliminary observations on the use of ertugliflozin (below)
Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are used to treat diabetes mellitus in humans. They work by reducing the reabsorption of glucose in the kidneys (by blocking SGLT-2 reabsorption of glucose), causing glucose to be excreted from the body in the urine. This lowers blood glucose concentrations and therefore insulin concentrations are reduced. No SGLT-2 medicines are licensed for horses as at 2022. Consequently there is no official reporting for side effects in horses, and interactions with other medications may not be known SGLT-2 medicines currently being given to horses with insulin dysregulation include Canagliflozin (sold under the trade name Invokana), Ertugliflozin and Velagliflozin.
Please read this imporant information from the Equine Endocrinology Group before using SGLT-2 inhibitors e.g. Ertugliflozin, Invokana/Canagliflozin, Velagliflozin:
Under the heading Medical Therapy on page 14 of Recommendations for the Diagnosis and Treatment of Equine Metabolic Syndrome (EMS) 2022 Equine Endocrinology Group
"Sodium-glucose co-transporter 2 (SGLT2) inhibitors
Indications: Used when horses are affected by laminitis and severe ID are not responding to other measures, and the owner has sufficient resources to pay for an expensive medical treatment. Drugs in this group act by inhibiting the reuptake of glucose from the glomerular filtrate, with more glucose lost in the urine as a result. Blood glucose concentrations decrease in response to treatment, and the amount of insulin needed to maintain euglycemia decreases proportionally. In initial studies in ponies, blood insulin concentrations significantly decreased over time when the SGLT2 inhibitor velagliflozin was administered orally at a dose of 0.3 mg/kg every 24 hours. Velagliflozin is not available for purchase at present, but two drugs in the same group, canagliflozin (0.5 mg/kg, PO, q24h) and ertugliflozin (0.05 mg/kg POq24h), are available. They are labeled for the treatment of diabetes mellitus in humans. Both drugs have been used with some success in a small number of horses with severe ID, but they are expensive in some countries and are reserved for horses with laminitis and severe ID that do not respond to recommended management changes. Smaller equids may be treated at a more reasonable cost. Lipid mobilization is stimulated in many horses treated with SGLT2 inhibitors, and hypertriglyceridemia might develop as a consequence. Thus, horses with marked hypertriglyceridemia should not be treated with these drugs.
Practice Tip: Although the SGLT2 inhibitors are promising drugs, it is essential that TG concentrations be monitored when treatment is initiated because individual horses might develop severe hypertriglyceridemia (>1,000 mg/dL; 26 mmol/L). Collect blood at 7 and 14 days, and then every 1-3 months thereafter. A risk/benefit assessment is needed if hypertriglyceridemia develops, and treatment decisions should be based on the severity of laminitis. Moderate hypertriglyceridemia (>100 mg/dL; 2.6 mmol/L) may affect the liver and other organs, and gamma glutamyl transferase (GGT) concentrations should be monitored if this problem develops. Management practices to address hyperinsulinemia must also be instituted at the same time, with the goal of discontinuing SGLT2 inhibitor treatment once the horse’s condition stabilizes. The EEG does not condone prescribing drugs for the treatment of ID without making appropriate management changes. The outcomes and health consequences of long-term treatment with SGLT2 inhibitors have not yet been evaluated in horses so these drugs should only be used in the short term (three months) until more research has been performed."
Ertugliflozin appears to be the most commonly prescribed SGLT-2 inhibitor for horses in the UK as at 2022.
See BEVA Client Information Leaflet Ertugliflozin published 10 February 2022
Research
Sundra T, Kelty E, Rendle D
Preliminary observations on the use of ertugliflozin in the management of hyperinsulinaemia and laminitis in 51 horses: A case series
BEVA Equine Veterinary Education published online 17 November 2022. https://doi.org/10.1111/eve.13738. Open Access.
See also EVE Video Abstract No. 27 Preliminary observations on the use of ertugliflozin (below)
Kellon EM, Gustafson KM.
Use of the SGLT2 inhibitor canagliflozin for control of refractory equine hyperinsulinemia and laminitis.
Open Vet J. 2022 Jul-Aug;12(4):511-518. doi: 10.5455/OVJ.2022.v12.i4.14. Epub 2022 Aug 7. PMID: 36118716; PMCID: PMC9473365.
"In conclusion, once daily administration of the SGLT2 inhibitor canagliflozin corrected hyperglycemia, reduced insulin to normal or near normal levels, and was 100% effective in reversing or reducing abnormal fat pads and eliminating laminitis pain in horses with refractory hyperinsulinemia and laminitis. There were no drug refusals. The expected polyuria was noted, which was mild. Despite its effectiveness, increases in insulin were observed when concomitant PPID was not controlled or diet was liberalized. It is recommended that the core aspects of therapy - diet control, exercise when possible and adequate treatment of PPID - must also be maintained if using canagliflozin. Furthermore, since these modalities are often successful themselves, canagliflozin should be reserved for refractory cases. Further controlled trials to investigate cangliflozin pharmacokinetics, pharmacodynamics, efficacy, safety, and long-term use in horses are needed."
Frank N
Safety and Efficacy of Canagliflozin and Octreotide for Managing Insulin Dysregulation in Horses
J Vet Intern Med. 2018 Nov-Dec; 32(6): 2123–2143 (Online Oct 2018). doi: 10.1111/jvim.15314
(ACVIM 2018 Forum Research Report Program, Seattle, Washington, June 2018)
6 horses received Canagliflozin (an SGLT2 inhibitor) and Octreotide (a somatostatin analog) for 3 days at 3 doses in a crossover design. An OST was carried out before the first dose and 24 hours after the third dose of drugs. OST areas under the curve did not change significantly at the low Canagliflozin dose, but significantly decreased with medium and high Canafliflozin treatment. No adverse health effects were seen. The presentation concluded "We provide evidence that Canagliflozin improves insulin dynamics in horses with ID after administration of only 3 doses and this drug warrants further investigation as a strategy for preventing laminitis."
Meier A, de Laat M, Reiche D, Fitzgerald D, Sillence M
The efficacy and safety of velagliflozin over 16 weeks as a treatment for insulin dysregulation in ponies
BMC Vet Res February 2019 15, 65. https://doi.org/10.1186/s12917-019-1811-2
Meier A, Reiche D, de Laat M, Pollitt C, Walsh D, Sillence M
The sodium-glucose co-transporter 2 inhibitor velagliflozin reduces hyperinsulinemia and prevents laminitis in insulin-dysregulated ponies
PLOS ONE September 2018 13(9). https://doi.org/10.1371/journal.pone.0203655
29 horses were fed a high NSC diet with no treatment, 12 horses were fed a high NSC diet and treated wtih velagliflozin. The treated group had insulin around 150 uIU/ml and none developed laminitis. The control group had insulin around 272 uIU/ml and 11/29 (38%) developed laminitis, suggesting that treatment with velagliflozin reduces the onset of laminitis WHEN HORSES ARE FED A HIGH NSC DIET (which they shouldn't be if at risk of insulin dysregulation).
Side effects listed for humans include:
Increased risk of leg amputations
Dehydration and decreased kidney function
Ketoacidosis
Genital yeast infections/thrush
Urinary tract infections
Low blood sugar
Low blood pressure
Necrotizing fasciitis
Allergic reaction
Bone fractures
Polyuria
Constipation
Nausea
Increases in LDL cholesterol
Increased risk of heart attack and stroke (during first month of treatment)
Source: Invokana (canagliflozin) tablets
Diabetes.co.uk
Interactions between SGLT-2 inhibitors and other drugs (for humans):
Drugs.com - Invokana Drug Interactions
Drugs listed include corticosteroids, and turmeric.
TLS comment: As at 2022 we have seen reports of horses taking Invokana having abnormally high triglycerides. TLS recommends that triglycerides and kidney function enzymes are closely monitored during Invokana use, and the horse's vet informed immediately if loss of appetite or dullness is noticed (as these could be clinical signs of hyperlipaemia, a potentially fatal condition). Horses with liver or kidney disease or high triglycerides should not be given SGLT-2 inhibitors. Ensure the prescribing vet is aware of all medications and supplements a horse is receiving while undergoing treatment with SGLT-2 inhibitors.
Sheath - swelling and smegma as possible indicators of insulin dysregulation
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Swelling of the sheath and/or increased smegma (a wax-like substance produced by the inside of the sheath) have been reported by many owners as indicators of insulin dysregulation (ID) in their geldings, with an increase in swelling often preceding an episode of laminitis.
The smegma tends to be black/grey, thick, greasy and strong smelling, and may be seen on the inner hind leg after the horse has been lying down.
Owners often think that excessive smegma is normal for their horse, then notice an improvement when the horse is treated for PPID/ID. Both the swelling and smegma usually disappear as the diet is tightened, the horse loses weight and/or the ID is controlled.
Many owners of ID horses check their gelding's sheath as well as neck crest and supraorbital sockets daily for signs of swelling, and take immediate action to tighten diet if any swelling or excess smegma is noticed. Owners have reported seeing very rapid (24 hours or less) changes in sheath size.
A swollen sheath is often thought to be due to an infection, and this should of course be ruled out, but when a swollen sheath appears with signs of laminitis, insulin dysregulation should always be considered. Keeping the sheath clean should lessen the chance of infection.
It has been suggested that the sheath swelling is related to adipose (fat) tissue accumulation, which interferes with lymphatic flow. The swelling may develop when a horse is on box rest, and resolve with exercise. See Guide to Insulin Resistance and Laminitis for Equine Practitioners page 24/25.
Sheath Swelling or Enlargement - www.horsesidevetguide.com
"The sheath also often becomes very fatty in overweight and insulin resistant horses. Sometimes distinguishing between a fat sheath and a swollen sheath can be difficult."
Sheath care for geldings - XL Vets Equine
Sheaths may need to be cleaned every 2 to 4 weeks with warm water, or KY jelly applied inside the sheath to loosen smegma. Avoid overcleaning, which may cause fungal overgrowth, but avoid excessive build up of smegma, which can cause discomfort, swelling or infection.
According to XLEquine " Smegma build up is more common in the winter, especially if a horse is overweight as fat is partly stored in the sheath. Older geldings frequently have mildly swollen sheaths in the winter as they move around less and circulation in the sheath becomes poorer in the cold weather."
Professional sheath cleaner Tracey Freeman of Sheath Cleaning UK uses KY Jelly, and wears vinyl (never latex) gloves.
The smegma tends to be black/grey, thick, greasy and strong smelling, and may be seen on the inner hind leg after the horse has been lying down.
Owners often think that excessive smegma is normal for their horse, then notice an improvement when the horse is treated for PPID/ID. Both the swelling and smegma usually disappear as the diet is tightened, the horse loses weight and/or the ID is controlled.
Many owners of ID horses check their gelding's sheath as well as neck crest and supraorbital sockets daily for signs of swelling, and take immediate action to tighten diet if any swelling or excess smegma is noticed. Owners have reported seeing very rapid (24 hours or less) changes in sheath size.
A swollen sheath is often thought to be due to an infection, and this should of course be ruled out, but when a swollen sheath appears with signs of laminitis, insulin dysregulation should always be considered. Keeping the sheath clean should lessen the chance of infection.
It has been suggested that the sheath swelling is related to adipose (fat) tissue accumulation, which interferes with lymphatic flow. The swelling may develop when a horse is on box rest, and resolve with exercise. See Guide to Insulin Resistance and Laminitis for Equine Practitioners page 24/25.
Sheath Swelling or Enlargement - www.horsesidevetguide.com
"The sheath also often becomes very fatty in overweight and insulin resistant horses. Sometimes distinguishing between a fat sheath and a swollen sheath can be difficult."
Sheath care for geldings - XL Vets Equine
Sheaths may need to be cleaned every 2 to 4 weeks with warm water, or KY jelly applied inside the sheath to loosen smegma. Avoid overcleaning, which may cause fungal overgrowth, but avoid excessive build up of smegma, which can cause discomfort, swelling or infection.
According to XLEquine " Smegma build up is more common in the winter, especially if a horse is overweight as fat is partly stored in the sheath. Older geldings frequently have mildly swollen sheaths in the winter as they move around less and circulation in the sheath becomes poorer in the cold weather."
Professional sheath cleaner Tracey Freeman of Sheath Cleaning UK uses KY Jelly, and wears vinyl (never latex) gloves.
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Sinusitis
Sinusitis is one of the more common infections seen in horses with PPID - abscesses, skin and lung infections are also reported. According to Dianne McFarlane*, opportunistic infections - that's an infection that wouldn't normally cause disease in a healthy horse, but does in a horse with an impaired immune system - were seen in around 35% of horses with PPID in one study. Several of the hormones produced in excess in PPID horses -ACTH, alpha-MSH and beta-endorphin - suppress the immune system. White blood cell function may be impaired in horses with PPID, and horses with PPID were found to have "increased expression of IL-8, which may influence the ability of horses with PPID to respond to bacterial pathogens" - McFarlane & Holbrook**. Primary sinusitis is usually reported as being unilateral (in one sinus/nostril only) and odourless, but in the cases TLS has seen of sinusitis in horses with PPID, the yellow/creamy coloured discharge has been distinctly unpleasant smelling, and has been bilateral (from both sinuses/nostrils). Usual causes of sinusitis are primary bacterial or fungal/mycotic infection, or secondary due to dental disease (also facial trauma, cysts and neoplasia). Treatment for sinusitis should involve ensuring that the PPID is well under control, by monitoring ACTH and other clinical symptoms, establishing the cause and treating appropriately. |
*McFarlane D
Equine pituitary pars intermedia dysfunction Vet Clin North Am Equine Pract. 2011 Apr;27(1):93-113 (Google Books) **McFarlane D, Holbrook TC Cytokine dysregulation in aged horses and horses with pituitary pars intermedia dysfunction. J Vet Intern Med. 2008 Mar-Apr;22(2):436-42. |
Disorders of the Paranasal Sinuses - Henry Tremaine and David E Freeman
Diseases of the Nasal Cavities and Paranasal Sinuses
W. H. Tremaine and P. M. Dixon - March 2002
Sinusitis - George Vet Group
12th WEVA Congress 2011
Treatment of equine sinusitis
PM Dixon
One-Sided Runny Nose: Is Sinusitis to Blame? Stacey Oke - www.thehorse.com Dec 2011
Diseases of the Nasal Cavities and Paranasal Sinuses
W. H. Tremaine and P. M. Dixon - March 2002
Sinusitis - George Vet Group
12th WEVA Congress 2011
Treatment of equine sinusitis
PM Dixon
One-Sided Runny Nose: Is Sinusitis to Blame? Stacey Oke - www.thehorse.com Dec 2011
Somatostatin
Somatostatin binds to receptors on pancreatic Islet cells to inhibit the secretion of insulin, glucago and pancreatic polypeptide.
Frank N, Hermida P, Sanchez-Londoño A, Singh R, Gradil CM, Uricchio CK
Blood Glucose and Insulin Concentrations after Octreotide Administration in Horses With Insulin Dysregulation
J Vet Intern Med. 2017 Jul;31(4):1188-1192. doi: 10.1111/jvim.14718. Epub 2017 May 15
Somatostatin binds to receptors on pancreatic Islet cells to inhibit the secretion of insulin, glucago and pancreatic polypeptide.
Frank N, Hermida P, Sanchez-Londoño A, Singh R, Gradil CM, Uricchio CK
Blood Glucose and Insulin Concentrations after Octreotide Administration in Horses With Insulin Dysregulation
J Vet Intern Med. 2017 Jul;31(4):1188-1192. doi: 10.1111/jvim.14718. Epub 2017 May 15
Spirulina
Nawrocka D, Kornicka K, Śmieszek A, Marycz K
Spirulina platensis Improves Mitochondrial Function Impaired by Elevated Oxidative Stress in Adipose-Derived Mesenchymal Stromal Cells (ASCs) and Intestinal Epithelial Cells (IECs), and Enhances Insulin Sensitivity in Equine Metabolic Syndrome (EMS) Horses
Marine Drugs Aug 2017, 15(8), 237; doi:10.3390/md15080237
See also Does Spirulina Benefit Horses With EMS? Casie Bazay, www.thehorse.com Nov 2017
For 3 months 500 g of pelleted spirulina (composition not given) was fed to 6 obese EMS horses, plus 1.5% bodyweight Timothy hay; 6 healthy horses and 6 obese EMS horses were fed 500 g of hay pellets, plus 1.5% bodyweight Timothy hay.
Why feed spirulina to horses - ForagePlus June 2015
Sphingolipids
Jorge-Smeding E, Warnken T, Grob AJ, Feige K, Pudert T, Leung YH, Go YY, Kenez A.
The sphingolipidome of plasma, liver, and adipose tissues and its association with insulin response to oral glucose testing in Icelandic horses.
Am J Physiol Regul Integr Comp Physiol. Published online 08 August 2022. doi: 10.1152/ajpregu.00018.2022. Full paper Deepdyve.
Leung YH, Kenéz Á, Grob AJ, Feige K, Warnken T.
Associations of plasma sphingolipid profiles with insulin response during oral glucose testing in Icelandic horses.
J Vet Intern Med. 2021 Jul;35(4):2009-2018. doi: 10.1111/jvim.16200. Epub 2021 Jun 8.
Jorge-Smeding E, Warnken T, Grob AJ, Feige K, Pudert T, Leung YH, Go YY, Kenez A.
The sphingolipidome of plasma, liver, and adipose tissues and its association with insulin response to oral glucose testing in Icelandic horses.
Am J Physiol Regul Integr Comp Physiol. Published online 08 August 2022. doi: 10.1152/ajpregu.00018.2022. Full paper Deepdyve.
Leung YH, Kenéz Á, Grob AJ, Feige K, Warnken T.
Associations of plasma sphingolipid profiles with insulin response during oral glucose testing in Icelandic horses.
J Vet Intern Med. 2021 Jul;35(4):2009-2018. doi: 10.1111/jvim.16200. Epub 2021 Jun 8.
Stevia/Stevioside
Elzinga SE, Rohleder B, Schanbacher B, McQuerry K, Barker VD, Adams AA
Metabolic and inflammatory responses to the common sweetener stevioside and a glycemic challenge in horses with equine metabolic syndrome
Domest Anim Endocrinol. 2017 Feb 4;60:1-8. doi: 10.1016/j.domaniend.2017.01.001
Elzinga SE, Rohleder B, Schanbacher B, McQuerry K, Barker VD, Adams AA
Metabolic and inflammatory responses to the common sweetener stevioside and a glycemic challenge in horses with equine metabolic syndrome
Domest Anim Endocrinol. 2017 Feb 4;60:1-8. doi: 10.1016/j.domaniend.2017.01.001
Stress
How much is stress involved in laminitis?
How much does stress affect blood test results?
Stress - from illness, pain, exercise, transport, being twitched, needle phobia.... - may affect ACTH results:
Does a high ACTH result mean my horse has PPID?
Heitman K, Rabquer B, Heitman E, Streu C, Anderson P
The Use of Lavender Aromatherapy to Relieve Stress in Trailered Horses
JEVS published online 04 January 2018
"Transporting horses via horse trailer increases heart rate and serum cortisol levels."
Ille N, Aurich C, Aurich J
Physiological stress response of mares to gynecological examination in veterinary medicine
JEVS published online Apr 2016
Gynecological examination caused heart rate and salivary cortisol levels to increase,
Budzyńska Monika
Stress reactivity and coping in horse adaptation to environment
Journal of Equine Veterinary Science published online 26 May 2014
Vreeman, Hendrike
The twitch in donkeys
(2009) Faculty of Veterinary Medicine Thesis
The use of a twitch significantly increased ACTH and cortisol, suggesting an increased stress response.
How much is stress involved in laminitis?
How much does stress affect blood test results?
Stress - from illness, pain, exercise, transport, being twitched, needle phobia.... - may affect ACTH results:
Does a high ACTH result mean my horse has PPID?
Heitman K, Rabquer B, Heitman E, Streu C, Anderson P
The Use of Lavender Aromatherapy to Relieve Stress in Trailered Horses
JEVS published online 04 January 2018
"Transporting horses via horse trailer increases heart rate and serum cortisol levels."
Ille N, Aurich C, Aurich J
Physiological stress response of mares to gynecological examination in veterinary medicine
JEVS published online Apr 2016
Gynecological examination caused heart rate and salivary cortisol levels to increase,
Budzyńska Monika
Stress reactivity and coping in horse adaptation to environment
Journal of Equine Veterinary Science published online 26 May 2014
Vreeman, Hendrike
The twitch in donkeys
(2009) Faculty of Veterinary Medicine Thesis
The use of a twitch significantly increased ACTH and cortisol, suggesting an increased stress response.
Sugar and Starch
Sugars are carbohydrates (simple carbohydrates), and are either:
monosaccharides - glucose and fructose (and galactose, mannose, arabinose and xylose), or
disaccharides - sucrose, maltose and lactose
Monosaccharides can be absorbed from the intestine without digestive enzyme activity. Glucose is the major sugar found in blood and can be used by all body tissue as an energy source, converted to glycogen for storage, converted to amino acids or converted to fat.
Sugars are water soluble and ethanol soluble - they are included in both ESC and WSC (and NSC which is WSC plus starch).
Sugars are hydrolyzable - they are digested by enzymes in the small intestine (and can also be fermented by microorganisms in the stomach and small and large intestine)
Some analyses include fructans in "sugars" - it is important to differentiate between simple sugars (glucose, fructose & sucrose - ESC) and fructans (approximately WSC - ESC), as the horse digests these in different ways (sugars and starch are hydrolyzed in the small intestine, fructans are fermented in the large intestine). For this reason, the use of the plant nomenclature WSC and NSC are unsuitable for horses, and The Laminitis Site suggests that carbohydrates should be divided into hydrolyzable carbohydrates and fermentable carbohydrates.
Sucrose is the main sugar in the sap of plants. C3 grasses convert sucrose into fructans for storage in leaves and stems, and into starch for storage in seeds.
Source: Nutritional Ecology of the Ruminant - Peter J Van Soest 1994
J Anim Sci. 2001 Feb;79(2):500-6
Hydrolyzable carbohydrates in pasture, hay, and horse feeds: direct assay and seasonal variation
Hoffman RM, Wilson JA, Kronfeld DS, Cooper WL, Lawrence LA, Sklan D, Harris PA
Starch overload can lead to acidosis and sepsis associated laminitis.
How much starch is likely to cause starch overload?
Hydrolyzable carbohydrates (CHO-H) may be fermented in the hind gut if starch intake exceeds 0.4% of bodyweight per feeding (so 2 kg per meal per 500 kg horse ) - Potter et al. Digestion of starch in the small or large intestine of the equine 1992.
Dyer et al. (2009) fed 6 Standard bred horses 3 diets:
1. 2% bodyweight Timothy hay plus minerals and vitamins for 3 months (WSC 4.9%, starch 2.1%, NDF 44.1%, CP 11.0%),
2. then 60% hay 40% grain (2/3 oats, 1/3 corn) with a starch content of 3.3 g/kg bw/d (WSC 2.3%, starch 18.1%, NDF 39.9%, CP 11.4%),
3. then 40% hay 60% grain with a starch content of 6.0 g/kg bw/d (WSC 1.5%, starch 32.9%, NDF 32.5%, CP 11.3%).
All diets were divided into 3 equal meals/day. Throughout and after the research period, the horses remained healthy.
Horses routinely fed diets with a high starch content had an increased capacity for glucose absorption compared to horses on a grass diet, due to an increase in SGLT-1 transporters in the small intestine. "In response to increased dietary carbohydrate, there is a coordinated enhancement in the rate of glucose transport across the luminal and basolateral membrane of equine enterocytes resulting in enhanced transcellular transport of glucose from the lumen of the intestine into the blood."
Dyer J, Al-Rammahi M, Waterfall L, Salmon KS, Geor RJ, Bouré L, Edwards GB, Proudman CJ, Shirazi-Beechey SP
Adaptive response of equine intestinal Na+/glucose co-transporter (SGLT1) to an increase in dietary soluble carbohydrate
Pflugers Arch. 2009 Jun;458(2):419-30. doi: 10.1007/s00424-008-0620-4. Epub 2008 Dec 2
Sugar/starch transporters
Sugar and starch move from food ingested into the horse through the gut wall to the blood via transporters (SGLT-1, GLUT5, GLUT2). See Transporters for more details.
monosaccharides - glucose and fructose (and galactose, mannose, arabinose and xylose), or
disaccharides - sucrose, maltose and lactose
Monosaccharides can be absorbed from the intestine without digestive enzyme activity. Glucose is the major sugar found in blood and can be used by all body tissue as an energy source, converted to glycogen for storage, converted to amino acids or converted to fat.
Sugars are water soluble and ethanol soluble - they are included in both ESC and WSC (and NSC which is WSC plus starch).
Sugars are hydrolyzable - they are digested by enzymes in the small intestine (and can also be fermented by microorganisms in the stomach and small and large intestine)
Some analyses include fructans in "sugars" - it is important to differentiate between simple sugars (glucose, fructose & sucrose - ESC) and fructans (approximately WSC - ESC), as the horse digests these in different ways (sugars and starch are hydrolyzed in the small intestine, fructans are fermented in the large intestine). For this reason, the use of the plant nomenclature WSC and NSC are unsuitable for horses, and The Laminitis Site suggests that carbohydrates should be divided into hydrolyzable carbohydrates and fermentable carbohydrates.
Sucrose is the main sugar in the sap of plants. C3 grasses convert sucrose into fructans for storage in leaves and stems, and into starch for storage in seeds.
Source: Nutritional Ecology of the Ruminant - Peter J Van Soest 1994
J Anim Sci. 2001 Feb;79(2):500-6
Hydrolyzable carbohydrates in pasture, hay, and horse feeds: direct assay and seasonal variation
Hoffman RM, Wilson JA, Kronfeld DS, Cooper WL, Lawrence LA, Sklan D, Harris PA
Starch overload can lead to acidosis and sepsis associated laminitis.
How much starch is likely to cause starch overload?
Hydrolyzable carbohydrates (CHO-H) may be fermented in the hind gut if starch intake exceeds 0.4% of bodyweight per feeding (so 2 kg per meal per 500 kg horse ) - Potter et al. Digestion of starch in the small or large intestine of the equine 1992.
Dyer et al. (2009) fed 6 Standard bred horses 3 diets:
1. 2% bodyweight Timothy hay plus minerals and vitamins for 3 months (WSC 4.9%, starch 2.1%, NDF 44.1%, CP 11.0%),
2. then 60% hay 40% grain (2/3 oats, 1/3 corn) with a starch content of 3.3 g/kg bw/d (WSC 2.3%, starch 18.1%, NDF 39.9%, CP 11.4%),
3. then 40% hay 60% grain with a starch content of 6.0 g/kg bw/d (WSC 1.5%, starch 32.9%, NDF 32.5%, CP 11.3%).
All diets were divided into 3 equal meals/day. Throughout and after the research period, the horses remained healthy.
Horses routinely fed diets with a high starch content had an increased capacity for glucose absorption compared to horses on a grass diet, due to an increase in SGLT-1 transporters in the small intestine. "In response to increased dietary carbohydrate, there is a coordinated enhancement in the rate of glucose transport across the luminal and basolateral membrane of equine enterocytes resulting in enhanced transcellular transport of glucose from the lumen of the intestine into the blood."
Dyer J, Al-Rammahi M, Waterfall L, Salmon KS, Geor RJ, Bouré L, Edwards GB, Proudman CJ, Shirazi-Beechey SP
Adaptive response of equine intestinal Na+/glucose co-transporter (SGLT1) to an increase in dietary soluble carbohydrate
Pflugers Arch. 2009 Jun;458(2):419-30. doi: 10.1007/s00424-008-0620-4. Epub 2008 Dec 2
Sugar/starch transporters
Sugar and starch move from food ingested into the horse through the gut wall to the blood via transporters (SGLT-1, GLUT5, GLUT2). See Transporters for more details.
Support and advice
The Laminitis Site's support and discussion group is open to Friends of The Laminitis Site - join here: Join Friends of TLS
The Equine Cushing’s and Insulin Resistance Group co-owned by Dr Eleanor Kellon VMD based in USA
Website: www.ecirhorse.com
The Equine Cushing’s and Insulin Resistance Group co-owned by Dr Eleanor Kellon VMD based in USA
Website: www.ecirhorse.com
Supporting Limb Laminitis (SLL)
Supporting limb laminitis (SLL) generally develops in the foot opposite to a leg which has a severe non-weight bearing lameness, often due to a fracture, joint infection or tendon injury, or any condition that results in a long-term severe lameness in one leg with excessive weight-bearing on a supporting leg. Both severity and duration of the primary lameness are likely to increase the risk of SLL. Barbaro, winner of the 2006 Kentucky Derby, fractured his right hind and developed SLL 2 months later. He recovered, but a further operation led to laminitis in both front feet and he was put to sleep.
SLL occurs due to lack of blood perfusion. Research published in 2021 (van Eps et al. 2021) suggests that rather than increased limb weight-bearing load, SLL may be caused by altered ambulatory patterns (specifically reduced limb load cycling frequency/lack of movement) interfering with blood perfusion sufficiently to damage the lamellae. "This damage is not confined to the supporting limb, but rather occurs in multiple limbs and may be subclinical."
SLL usually presents with acute lameness and rapid and catastrophic lamellar failure, but it can also be chronic, with signs of SLL sometimes not being seen until the primary lameness has resolved. Once clinical signs of SLL are seen, lesions are usually well advanced and recovery is unlikely.
Earlier research show reduced blood supply (ischemia) to the laminae within 2-3 days of excessive weight-bearing on a front leg. Dr Andrew van Eps and the van Eps Laminitis Laboratory have demonstrated the importance of load and load cycling on blood perfusion in the foot, which suggests an important role for ischemia in supporting limb laminitis. The van Eps laboratory is focusing on methods to prevent perfusion failure in SLL, suggesting that prevention of SLL is key, and that monitoring and enhancement of limb load cycling are key strategies for the prevention of SLL.
SLL occurs due to lack of blood perfusion. Research published in 2021 (van Eps et al. 2021) suggests that rather than increased limb weight-bearing load, SLL may be caused by altered ambulatory patterns (specifically reduced limb load cycling frequency/lack of movement) interfering with blood perfusion sufficiently to damage the lamellae. "This damage is not confined to the supporting limb, but rather occurs in multiple limbs and may be subclinical."
SLL usually presents with acute lameness and rapid and catastrophic lamellar failure, but it can also be chronic, with signs of SLL sometimes not being seen until the primary lameness has resolved. Once clinical signs of SLL are seen, lesions are usually well advanced and recovery is unlikely.
Earlier research show reduced blood supply (ischemia) to the laminae within 2-3 days of excessive weight-bearing on a front leg. Dr Andrew van Eps and the van Eps Laminitis Laboratory have demonstrated the importance of load and load cycling on blood perfusion in the foot, which suggests an important role for ischemia in supporting limb laminitis. The van Eps laboratory is focusing on methods to prevent perfusion failure in SLL, suggesting that prevention of SLL is key, and that monitoring and enhancement of limb load cycling are key strategies for the prevention of SLL.
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Notes from Dr Andrew Van Eps video (left):
SLL is due to a lack of blood perfusion that occurs secondary to a lack of movement on the limb. Research is going to focus on detecting a lack of normal motion in the limbs of horses hospitalized for fractures and other painful limb conditions. We need to be able to detect this risk very early. Research will look at tissues to see why tissue is getting damaged - we know it's a lack of blood perfusion but we need to find the mechanisms of the cell death as some mechanisms may be preventable. There is good data showing that even in legs that are overloaded e.g. due to a fracture in a different leg, we may be able to enhance blood perfusion to the lamellar tissue. |
In all forms of laminitis, a combination of epithelial cell adhesion loss and epithelial cell stretch weakens the lamellar attachments, but whereas endocrinopathic laminitis is dominated by cell stretch, SLL (and sepsis-related laminitis) is dominated by adhesion loss.
Horses that are able to weight the primarily lame leg periodically appear to be at less risk of developing SLL than horses that will not bear weight on the primarily lame leg at all. Increased body weight and poor feet may increase the risk of non-weight-bearing lame horses developing SLL.
Prevention and treatment measures may include:
- using a sling to support the horse's weight,
- managing both orthopedic and neuropathic pain with some combination of NSAIDs and other pain medications and possibly local nerve blocks or pain relief, to encourage some weight bearing on the injured leg if safe to do so,
- ensuring the supporting limb is padded to the same height as casts or dressings on the injured limb,
- encouraging the horse to lie down as much as possible.
Most important would appear to be supporting all feet to maximize weight bearing surface, and if not using a sling, encouraging the horse to lie down. The use of thick wrestling mats wall to wall in the horse's stable may be considered, and/or deep conforming bedding. Plus keeping the feet trimmed for perfect alignment of the hoof capsule to the pedal bone, particularly keeping the toes short.
Should cryotherapy be used? Cryotherapy is commonly used to treat the leg affected with SLL. However, cryotherapy reduces circulation. SLL may be due to reduced circulation. Without good evidence of the benefits of using cryotherapy for SLL, this treatment may be contra-indicated.
Horses that are able to weight the primarily lame leg periodically appear to be at less risk of developing SLL than horses that will not bear weight on the primarily lame leg at all. Increased body weight and poor feet may increase the risk of non-weight-bearing lame horses developing SLL.
Prevention and treatment measures may include:
- using a sling to support the horse's weight,
- managing both orthopedic and neuropathic pain with some combination of NSAIDs and other pain medications and possibly local nerve blocks or pain relief, to encourage some weight bearing on the injured leg if safe to do so,
- ensuring the supporting limb is padded to the same height as casts or dressings on the injured limb,
- encouraging the horse to lie down as much as possible.
Most important would appear to be supporting all feet to maximize weight bearing surface, and if not using a sling, encouraging the horse to lie down. The use of thick wrestling mats wall to wall in the horse's stable may be considered, and/or deep conforming bedding. Plus keeping the feet trimmed for perfect alignment of the hoof capsule to the pedal bone, particularly keeping the toes short.
Should cryotherapy be used? Cryotherapy is commonly used to treat the leg affected with SLL. However, cryotherapy reduces circulation. SLL may be due to reduced circulation. Without good evidence of the benefits of using cryotherapy for SLL, this treatment may be contra-indicated.
Research:
Burns TA, Watts MR, Belknap JK, van Eps AW.
Digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearing.
J Vet Intern Med. Feb 2023 (online). doi: 10.1111/jvim.16662. Open Access.
Keywords: JAK/STAT; cytokines; inflammation; ischemia; stretch
Elliott J, Bailey SR.
A review ofcellular and molecular mechanisms in endocrinopathic, sepsis-related and supporting limb equine laminitis.
Equine Vet J. Published online 27 February 2023. doi: 10.1111/evj.13933. PMID: 36847165. Open Access.
Keywords: basal epithelial cell stress; horse; insulin dysregulation; laminitis pathogenesis; signalling pathways.
Holl HM, Armstrong C, Galantino-Homer H, Brooks SA
Transcriptome diversity and differential expression in supporting limb laminitis
Veterinary Immunology and Immunopathology 2022 Vol 243. https://doi.org/10.1016/j.vetimm.2021.110353
Van Eps A, Engiles J, Galantino-Homer H
Supporting Limb Laminitis
Veterinary Clinics of North America: Equine Practise published online 19 October 2021. https://doi.org/10.1016/j.cveq.2021.08.002
Key points:
"Supporting limb laminitis (SLL) is an important complication of conditions that cause protracted pain in one or more limbs.
Unlike laminitis associated with sepsis or hyperinsulinemia, ischemia is a key mechanistic event in the development of SLL, and as a result acute SLL lesions are unique.
Rather than increased limb weigh-bearing load, it appears that altered ambulatory patterns (specifically reduced limb load cycling frequency) may interfere with blood perfusion sufficiently to damage the lamellae. This damage is not confined to the supporting limb, but rather occurs in multiple limbs and may be subclinical.
Once SLL is clinically apparent, lesions are usually well advanced, making recovery unlikely; therefore, the focus should be on prevention.
Monitoring and enhancement of limb load cycling are key strategies for prevention of SLL."
Cassimeris L, Engiles JB, Galantino-Homer H.
Interleukin-17A pathway target genes are upregulated in Equus caballus supporting limb laminitis.
PLoS One. 2020;15(12):e0232920. Published 2020 Dec 10. doi:10.1371/journal.pone.0232920
S. L. Steinke, J. L. Carmalt, J. B. Montgomery
Weight reduction and possible implications for the rehabilitation of horses with ambulatory difficulties
Equine Veterinary Education published online: 01 November 2019
The latest on supporting limb laminitis - www.thehorse.com March 2018
No hoof, no horse: Ending the scourge of laminitis - Ed Kane, November 2017, dvm360.com
"convincing evidence that supporting-limb laminitis is a blood perfusion problem associated with load". When a horse preferentially places weight on a leg, it interferes with blood flow to the foot, and to properly perfuse the lamellar tissues, the horse must load and unload the leg. Prevention involves "providing partial, intermitten relief of weight-bearing on the support limb."
Gardner AK, van Eps AW, Watts MR, Burns TA, Belknap JK
A novel model to assess lamellar signaling relevant to preferential weight bearing in the horse
Vet J. 2017 Mar;221:62-67. doi: 10.1016/j.tvjl.2017.02.005. Epub 2017 Feb 14
8 healthy Standardbred horses were tied up for 48 hours with a v-shaped insert attached to the shoe of one fore foot to prevent normal weight bearing and force them to increase the load on the other supporting fore limb. Their lamellae were harvested and examined after 48 hours. Lamella mRNA concentrations of inflammatory signalling proteins did not differ between the supporting fore leg and the hind legs, but HIF-1α concentrations were greater in the supporting fore limb compared to the contralateral hind limb, suggesting that overloading one foot may cause lamellar hypoxia (decreased oxygen supply to the tissues) to occur.
AAEP Foundation Announces Funding of Research into Laminitis - Sept 2016
Hannah Galantino-Homer at the University of Pennsylvania will investigate the alterations that occur in the protein structure that supports the bone to the hoof connection. The goal is to understand the process of cell pathology in the foot to better predict, diagnose and treat support limb laminitis.
Samantha Brooks at the University of Florida seeks to understand the response of the cells in the support structures within the hoof. By utilizing RNA sequencing, genes that respond to the abnormal support in the foot will be identified and compared to normal feet. Understanding the gene upregulation will help identify the process within the hoof that leads to support failure. The research will use real-time PCR to identify the production of inflammatory mediators and enzymes involved with the pathology.
Medina-Torres CE, Underwood C, Pollitt CC, Castro-Olivera EM, Hodson MP, Richardson DW, van Eps AW
The effect of weightbearing and limb load cycling on equine lamellar perfusion and energy metabolism measured using tissue microdialysis
Equine Vet J. 2016 Jan;48(1):114-9. doi: 10.1111/evj.12377. Epub 2014 Dec 18
Mason JB, Gurda BL, Van Wettere A, Engiles JB, Wilson JM, Richardson DW
Delivery and evaluation of recombinant adeno-associated viral vectors in the equine distal extremity for the treatment of laminitis
Equine Vet J. 2015 Dec 11. doi: 10.1111/evj.12547. [Epub ahead of print]
"Our long-term aim is to develop a gene therapy approach for the prevention of laminitis in the contralateral foot of horses with major musculoskeletal injuries and non-weight-bearing lameness."
"Conclusions: The current experiments demonstrate that transgenes can be successfully delivered to the equine distal extremity using rAAV vectors and that serotypes 2/8, 2/9 and 2/1 can successfully transduce tissues of the equine foot. When the vector was diluted with surfactant-containing saline, the level of transduction increased dramatically. The increased level of transduction due to the addition of surfactant also improved the distribution pattern of transduction."
Wylie CE, Newton JR, Bathe AP, Payne RJ
Prevalence of supporting limb laminitis in a UK equine practice and referral hospital setting between 2005 and 2013: implications for future epidemiological studies
Vet Rec. 2015 Jan 17;176(3):72. doi: 10.1136/vr.102426. Epub 2014
Over 65,000 patient records at Rossdales Equine Practice were reviewed for cases of supporting limb laminitis (SLL) from Jan 2005 to Oct 2013. 11 cases were found - 9 horses, 1 pony, 1 donkey - 0.02% practice prevalence. 73% were Thoroughbreds, 9 were mares and 2 stallions. SLL was not restricted to horses that were non-weightbearing lame, it developed within 4-100 days after injury (median 14.5 days) and occurred most commonly in a forelimb (54.6 per cent, CI 25.1 to 84.0 per cent).
See also Supporting Limb Laminitis Uncommon, Researchers Find - Christa Lesté-Lasserre, www.thehorse.com Dec 2015
Gardner Alison K
Lamellar Mitogen-Activated Protein Kinase and Hypoxia Signaling in a Sepsis-Related Laminitis Model and a Novel Supporting Limb Laminitis Model
MSc thesis 2015 Ohio State University
Orsini, J. A.
Supporting limb laminitis: The four important ‘whys’
Equine Veterinary Journal, 44: 741–745 (2012)
Virgin JE, Goodrich LR, Baxter GM, Rao S
Incidence of support limb laminitis in horses treated with half limb, full limb or transfixation pin casts: a retrospective study of 113 horses (2000-2009).
Equine Vet J Suppl. 2011 Nov; 43 Suppl 40:7-11 (PubMed)
"CONCLUSIONS: Support limb laminitis is a relatively common complication among horses treated with half limb, full limb and transfixation pin casts. Greater durations of casting and higher bodyweights increase the likelihood of developing this complication.
POTENTIAL RELEVANCE: Support limb laminitis may occur secondary to any painful unilateral lameness and is not necessarily more likely to develop in horses with severe orthopaedic conditions such as fractures. However, heavier horses, those requiring casts for longer periods of time and those that require a full limb or transfixation pin cast as opposed to a half limb cast should be considered to have an increased risk for developing support limb laminitis post operatively."
van Eps A, Collins SN, Pollitt CC
Supporting limb laminitis
Vet Clin North Am Equine Pract. 2010 Aug;26(2):287-302. doi: 10.1016/j.cveq.2010.06.007
Baxter GM, Morrison S
Complications of unilateral weight bearing
Vet Clin North Am Equine Pract. 2008 Dec;24(3):621-42, ix. doi: 10.1016/j.cveq.2008.10.006 (DeepDyve)
Redden RF
Preventing Laminitis in the Contralateral Limb of Horses with Non–Weight-Bearing Lameness
AAEP Proceedings 2003
Burns TA, Watts MR, Belknap JK, van Eps AW.
Digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearing.
J Vet Intern Med. Feb 2023 (online). doi: 10.1111/jvim.16662. Open Access.
Keywords: JAK/STAT; cytokines; inflammation; ischemia; stretch
Elliott J, Bailey SR.
A review ofcellular and molecular mechanisms in endocrinopathic, sepsis-related and supporting limb equine laminitis.
Equine Vet J. Published online 27 February 2023. doi: 10.1111/evj.13933. PMID: 36847165. Open Access.
Keywords: basal epithelial cell stress; horse; insulin dysregulation; laminitis pathogenesis; signalling pathways.
Holl HM, Armstrong C, Galantino-Homer H, Brooks SA
Transcriptome diversity and differential expression in supporting limb laminitis
Veterinary Immunology and Immunopathology 2022 Vol 243. https://doi.org/10.1016/j.vetimm.2021.110353
Van Eps A, Engiles J, Galantino-Homer H
Supporting Limb Laminitis
Veterinary Clinics of North America: Equine Practise published online 19 October 2021. https://doi.org/10.1016/j.cveq.2021.08.002
Key points:
"Supporting limb laminitis (SLL) is an important complication of conditions that cause protracted pain in one or more limbs.
Unlike laminitis associated with sepsis or hyperinsulinemia, ischemia is a key mechanistic event in the development of SLL, and as a result acute SLL lesions are unique.
Rather than increased limb weigh-bearing load, it appears that altered ambulatory patterns (specifically reduced limb load cycling frequency) may interfere with blood perfusion sufficiently to damage the lamellae. This damage is not confined to the supporting limb, but rather occurs in multiple limbs and may be subclinical.
Once SLL is clinically apparent, lesions are usually well advanced, making recovery unlikely; therefore, the focus should be on prevention.
Monitoring and enhancement of limb load cycling are key strategies for prevention of SLL."
Cassimeris L, Engiles JB, Galantino-Homer H.
Interleukin-17A pathway target genes are upregulated in Equus caballus supporting limb laminitis.
PLoS One. 2020;15(12):e0232920. Published 2020 Dec 10. doi:10.1371/journal.pone.0232920
S. L. Steinke, J. L. Carmalt, J. B. Montgomery
Weight reduction and possible implications for the rehabilitation of horses with ambulatory difficulties
Equine Veterinary Education published online: 01 November 2019
The latest on supporting limb laminitis - www.thehorse.com March 2018
No hoof, no horse: Ending the scourge of laminitis - Ed Kane, November 2017, dvm360.com
"convincing evidence that supporting-limb laminitis is a blood perfusion problem associated with load". When a horse preferentially places weight on a leg, it interferes with blood flow to the foot, and to properly perfuse the lamellar tissues, the horse must load and unload the leg. Prevention involves "providing partial, intermitten relief of weight-bearing on the support limb."
Gardner AK, van Eps AW, Watts MR, Burns TA, Belknap JK
A novel model to assess lamellar signaling relevant to preferential weight bearing in the horse
Vet J. 2017 Mar;221:62-67. doi: 10.1016/j.tvjl.2017.02.005. Epub 2017 Feb 14
8 healthy Standardbred horses were tied up for 48 hours with a v-shaped insert attached to the shoe of one fore foot to prevent normal weight bearing and force them to increase the load on the other supporting fore limb. Their lamellae were harvested and examined after 48 hours. Lamella mRNA concentrations of inflammatory signalling proteins did not differ between the supporting fore leg and the hind legs, but HIF-1α concentrations were greater in the supporting fore limb compared to the contralateral hind limb, suggesting that overloading one foot may cause lamellar hypoxia (decreased oxygen supply to the tissues) to occur.
AAEP Foundation Announces Funding of Research into Laminitis - Sept 2016
Hannah Galantino-Homer at the University of Pennsylvania will investigate the alterations that occur in the protein structure that supports the bone to the hoof connection. The goal is to understand the process of cell pathology in the foot to better predict, diagnose and treat support limb laminitis.
Samantha Brooks at the University of Florida seeks to understand the response of the cells in the support structures within the hoof. By utilizing RNA sequencing, genes that respond to the abnormal support in the foot will be identified and compared to normal feet. Understanding the gene upregulation will help identify the process within the hoof that leads to support failure. The research will use real-time PCR to identify the production of inflammatory mediators and enzymes involved with the pathology.
Medina-Torres CE, Underwood C, Pollitt CC, Castro-Olivera EM, Hodson MP, Richardson DW, van Eps AW
The effect of weightbearing and limb load cycling on equine lamellar perfusion and energy metabolism measured using tissue microdialysis
Equine Vet J. 2016 Jan;48(1):114-9. doi: 10.1111/evj.12377. Epub 2014 Dec 18
Mason JB, Gurda BL, Van Wettere A, Engiles JB, Wilson JM, Richardson DW
Delivery and evaluation of recombinant adeno-associated viral vectors in the equine distal extremity for the treatment of laminitis
Equine Vet J. 2015 Dec 11. doi: 10.1111/evj.12547. [Epub ahead of print]
"Our long-term aim is to develop a gene therapy approach for the prevention of laminitis in the contralateral foot of horses with major musculoskeletal injuries and non-weight-bearing lameness."
"Conclusions: The current experiments demonstrate that transgenes can be successfully delivered to the equine distal extremity using rAAV vectors and that serotypes 2/8, 2/9 and 2/1 can successfully transduce tissues of the equine foot. When the vector was diluted with surfactant-containing saline, the level of transduction increased dramatically. The increased level of transduction due to the addition of surfactant also improved the distribution pattern of transduction."
Wylie CE, Newton JR, Bathe AP, Payne RJ
Prevalence of supporting limb laminitis in a UK equine practice and referral hospital setting between 2005 and 2013: implications for future epidemiological studies
Vet Rec. 2015 Jan 17;176(3):72. doi: 10.1136/vr.102426. Epub 2014
Over 65,000 patient records at Rossdales Equine Practice were reviewed for cases of supporting limb laminitis (SLL) from Jan 2005 to Oct 2013. 11 cases were found - 9 horses, 1 pony, 1 donkey - 0.02% practice prevalence. 73% were Thoroughbreds, 9 were mares and 2 stallions. SLL was not restricted to horses that were non-weightbearing lame, it developed within 4-100 days after injury (median 14.5 days) and occurred most commonly in a forelimb (54.6 per cent, CI 25.1 to 84.0 per cent).
See also Supporting Limb Laminitis Uncommon, Researchers Find - Christa Lesté-Lasserre, www.thehorse.com Dec 2015
Gardner Alison K
Lamellar Mitogen-Activated Protein Kinase and Hypoxia Signaling in a Sepsis-Related Laminitis Model and a Novel Supporting Limb Laminitis Model
MSc thesis 2015 Ohio State University
Orsini, J. A.
Supporting limb laminitis: The four important ‘whys’
Equine Veterinary Journal, 44: 741–745 (2012)
Virgin JE, Goodrich LR, Baxter GM, Rao S
Incidence of support limb laminitis in horses treated with half limb, full limb or transfixation pin casts: a retrospective study of 113 horses (2000-2009).
Equine Vet J Suppl. 2011 Nov; 43 Suppl 40:7-11 (PubMed)
"CONCLUSIONS: Support limb laminitis is a relatively common complication among horses treated with half limb, full limb and transfixation pin casts. Greater durations of casting and higher bodyweights increase the likelihood of developing this complication.
POTENTIAL RELEVANCE: Support limb laminitis may occur secondary to any painful unilateral lameness and is not necessarily more likely to develop in horses with severe orthopaedic conditions such as fractures. However, heavier horses, those requiring casts for longer periods of time and those that require a full limb or transfixation pin cast as opposed to a half limb cast should be considered to have an increased risk for developing support limb laminitis post operatively."
van Eps A, Collins SN, Pollitt CC
Supporting limb laminitis
Vet Clin North Am Equine Pract. 2010 Aug;26(2):287-302. doi: 10.1016/j.cveq.2010.06.007
Baxter GM, Morrison S
Complications of unilateral weight bearing
Vet Clin North Am Equine Pract. 2008 Dec;24(3):621-42, ix. doi: 10.1016/j.cveq.2008.10.006 (DeepDyve)
Redden RF
Preventing Laminitis in the Contralateral Limb of Horses with Non–Weight-Bearing Lameness
AAEP Proceedings 2003
 Fat in the supraorbital hollows
Supraorbital hollows/fossae
Horses with EMS and/or PPID often have fat in the supraorbital hollows above their eyes. |
Hollow (normal) supraorbital hollows - this is an old mare with sunken supraorbital hollows
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