The full paper is available:
Carmalt JL, Scansen BA
Development of two surgical approaches to the pituitary gland in the Horse
Vet Q. 2018 Dec;38(1):21-27. doi: 10.1080/01652176.2017.1415488 (PubMed)

Surgery for Equine Cushing’s Disease: A Possibility? KER Jan 2018

A major problem with this research is that the cause of PPID is not hyperplasia, hypertrophy or adenoma formation in the pituitary gland, it is loss of dopaminergic neurons in the hypothalamus.  Surgery on the pituitary gland will not reduce the primary cause of PPID.

Bear in mind that a lot of older research into PPID is based on untreated horses with advanced PPID - these horses may have had "grossly enlarged pituitary glands", but it is now being suggested that with earlier and better diagnosis of PPID, plus regular treatment with pergolide , either a constant low dose for several years (Schott H), or an initially higher dose that perhaps is reduced once symptoms are brought under control (Durham A), PPID may not progress to the advanced stage with hyperplasia and hypertrophy leading to adenoma formation.  

The paper suggests that daily treatment with oral pergolide is costly and "labor and management intensive".  Costly, yes, particularly when horses require higher doses of pergolide, and while the only licensed treatment for horses is Prascend.  However, the exclusive licence for Prascend expires in 2020 in the UK, and if other manufacturers enter the market, prices may come down.  "Labor and management intensive" - giving a daily pill to a horse, compared to serious, expensive and potentially life-threatening surgery?  Whilst it can be difficult to persuade some horses to take their daily medicine, how many owners would choose the latter - even if surgery was effective?  The authors suggest that giving daily pergolide to horses that are "extensively or pasture managed"  and "infrequently handled" may not be possible... frankly, such horses are probably fairly unlikely to have PPID diagnosed or to be treated for it if PPID were diagnosed.  Horses kept in these conditions are probably more likely to be young horses, and young horses don't get PPID.  The authors suggest that there is emotional stress for owners deailing with horses with a chronic ongoing disease.  But surgery to remove pituitary adenomas will not cure PPID (see below), and treatment with pergolide in many cases is extremely effective, allowing horses with PPID to live normal lives.  Are the authors identifying real problems?

Cushing's disease in dogs and humans is caused by a tumour in the pituitary gland. PPID in horses is caused by degeneration of dopamine-producing neurons in the hypothalamus (found in the lower part of the brain, above the pituitary gland), which, if not controlled through use of dopamine agonists like pergolide, can eventually lead to the formation of adenomas (benign tumours) in the pituitary gland. Prior to the formation of adenomas, an increase in the number and size of pars intermedia cells occurs because of the lack of stimulus to stop producing hormones - due to the reduced quantity of dopamine reaching the pituitary gland, the body is telling the pars intermedia to produce more hormones, and to do this, it has to increase its factory size...and eventually these increased cells form benign tumours called adenomas.

Removing these adenomas in cases of PPID will not stop the progression of PPID - it is the lack of dopamine that causes and drives the progression of PPID. There might be a short-term reduction in hormone output because the factory size has been reduced, but cells can often increase in number very quickly, so is it likely that cell numbers would quickly increase back to meet the hormone production the lack of dopamine is stimulating? Even if the surgery did help for a period of time, a horse would still need a treatment to replace the missing dopamine - so there is no way surgery could replace medical treatment. Well, not unless they could implant a slow-release dopamine replacement - that might be interesting.

The research was basically trying to find a surgical route to reach the pituitary gland in horses, which is perfectly reasonable.

The first attempts on cadavers were a myeloscopic approach which was abandoned due to too much bleeding, and a trans-sphenopalatine sinus approach that was abandoned due to inadequate access to the sinus, plus the proximity of the optic chiasm to the pituitary gland would make this technique unfeasible.  The pituitary gland was accessible with a ventral trans-basispheniodal osteotomy approach in cadaver heads, but when this was carried out on a live horse under anesthetic, a slip of the drill caused uncontrollable hemorrhage and the horse was euthanased.  An approach through the deep facial vein allowed access to the ventral cavernous sinus and the pituitary gland in cadaver heads.  This approach was then carried out on two live horses: access for a long flexible needle to the pituitary gland was achieved on one healthy horse, but on the other horse that had PPID, a needle injecting dye missed the pituitary gland and emptied into the cavernous sinus blood instead.  Both horses were euthanased while under the anesthetic, so recovery and adverse effects from this procedure are not known.  This procedure was technically demanding, with accurate positioning being critical, and possible additional complications including damage to blood vessels and nerves in the guttural pouch, with intractable dysphagia which can lead to pneumonia and death, and introduction of infection.  The authors note that this method would be likely to cause "collateral damage to the pars nervosa or pars distalis".

The authors state that it is not known how much surgical removal or cell destruction would be necessary to return a horse to being clinically normal, and that the goal would not be to remove all pars intermedia hormone output.  However, no mention is made of the fact that the pituitary abnormality is the result, not the cause, of PPID.  The authors state that "anything other that complete resolution of clinical signs will be unsuitable in the horse because there is already an oral daily medication for PPID" - but without daily medication to replace the dopamine not being produced by the hypothalamus, surely the cause of PPID will continue, and a horse could risk life threatening surgery for no great long-term improvement in clinical signs and continue to suffer from PPID.

The research is valuable for describing successful and unsuccessful approaches to the equine pituitary gland, but the article suggesting that this research "offers owners hope for viable alternatives to daily pergolide" is misleading.

​Jacob SI, Geor RJ, Weber PSD, Harris PA, McCue ME
Effect of dietary carbohydrates and time of year on ACTH and cortisol concentrations in adult and aged horses
Domest Anim Endocrinol. Published online 2017 Nov 1;63:15-22. doi: 10.1016/j.domaniend.2017.10.005

Abstract:Diagnosis of equine pituitary pars intermedia dysfunction (PPID) remains a challenge as multiple factors (stress, exercise, and time of year) influence ACTH and cortisol concentrations. To assess endocrine status in a study designed to evaluate the effects of age and diet on glucose and insulin dynamics, we performed thyrotropin-releasing hormone (TRH) stimulation tests and overnight dexamethasone suppression tests in March, May, August, and October on 16 healthy Thoroughbred and Standardbred mares and geldings. Horses were grouped by age: adult (mean ± SD; 8.8 ± 2.9 yr; n = 8) and aged (20.6 ± 2.1 yr; n = 8). None of the horses showed clinical signs (hypertrichosis, regional adiposity, skeletal muscle atrophy, lethargy) of pituitary pars intermedia dysfunction. Horses were randomly assigned to groups of 4, blocked for age, and fed grass hay plus 4 isocaloric concentrate diets (control, starch-rich, fiber-rich, and sugar-rich) using a balanced Latin square design. Data were analyzed using a multivariable linear mixed regression model. Baseline ACTH was significantly higher in aged horses (mean ± standard error of the mean; 60.0 ± 10.7 pg/mL) adapted to the starch-rich diet compared to adult horses (15.7 ± 12.0 pg/mL) on the same diet (P = 0.017). After controlling for age and diet, baseline ACTH concentrations were significantly increased in October (57.7 ± 7.1 pg/mL) compared to March (13.2 ± 7.1 pg/mL; P < 0.001), May (12.4 ± 7.1 pg/mL; P < 0.001), and August (24.2 ± 7.1 pg/mL; P < 0.001), whereas post-TRH ACTH was higher in August (376.6 ± 57.6 pg/mL) and October (370.9 ± 57.5 pg/mL) compared to March (101.9 ± 57.3 pg/mL; P < 0.001) and May (74.5 ± 57.1 pg/mL; P < 0.001). Aged horses had significantly higher post-dexamethasone cortisol on the starch-rich diet (0.6 ± 0.1 μg/dL) compared to the sugar-rich diet (0.2 ± 0.1 μg/dL; P = 0.021). Post-dexamethasone cortisol was significantly higher in October (0.6 ± 0.1 μg/dL) compared to March (0.3 ± 0.1 μg/dL; P = 0.005), May (0.2 ± 0.1 μg/dL; P < 0.001), and August (0.3 ± 0.1 μg/dL; P = 0.004). Breed did not influence ACTH or cortisol measurements. In conclusion, in addition to age and time of year, diet is a potential confounder as animals on a starch-rich diet may be incorrectly diagnosed with pituitary pars intermedia dysfunction.

Coleman M, Belknap J, Bramlage L, Eades S, Fraley B, Galantino-Homer H, Hunt R, Geor R, McCue M, McIlwraith W, Moore R, Peroni J, Townsend H, White N, Cummings K, Ivanek-Miojevic R, Cohen N
Case Control Study of Pasture and Endocrinopathy-Associated Laminitis in Horses
Equine Endocrinology Summit 2017 p 25

Significant efforts have been made in the past decade to further our understanding of laminitis in horses; however, much research has been limited to the study of the mechanistic pathways following experimental induction of disease. The conduct of observational studies of naturally-occurring laminitis is necessary for the improvement of our knowledge and understanding of disease predisposition and the design of future investigations into the prevention and control of this debilitating disease. Thus, the objective of this study was to determine risk factors for the development of pasture- and endocrinopathy-associated laminitis (PEAL) in horses evaluated by veterinarians in North America. In this case-control study, incident cases of PEAL evaluated by veterinary practitioners in North America from 2012- 2015 and horses from 2 control populations were included. Participating veterinarians provided historical data from a case of PEAL, a healthy control, and a lameness control. Conditional logistic regression analysis was used to compare data from PEAL-affected horses and each set of controls. A total of 199 horses with acute, incident PEAL, 198 healthy controls, and 153 lameness controls were included in the analysis.

Horses with an obese body condition (BCS ≥ 7), generalized or regional adiposity, a historic diagnosis of an endocrinopathy, and recent glucocorticoid administration were at increased odds of developing PEAL. 

Elucidating the determinants and earlier recognition of obesity, adiposity, and endocrinopathies might be a strategy for reducing the burden of this form of laminitis.

Update August 2018.  See also:
Coleman MC, Belknap JK, Eades SC, Galantino-Homer HL, Hunt RJ, Geor RJ, McCue ME, McIlwraith CW, Moore RM, Peroni JF, Townsend HG, White NA, Cummings KJ, Ivanek-Miojevic R, Cohen ND
Case-control study of risk factors for pasture-and endocrinopathy-associated laminitis in North American horses
J Am Vet Med Assoc. 2018 Aug 15;253(4):470-478. doi: 10.2460/javma.253.4.470

and The Laminitis Laboratory at New Bolton Center post 07 August 2018:
"Take-home bulletpoints from the study for risk factors for Pasture- and Endocrinopathy-Associated Laminitis (PEAL):
- Overweight body condition (BCS >/= 7 out of 9)
- Generalized or Regional adiposity (e.g., "cresty neck")
- Pre-existing endocrinopathy
- Not receiving concentrates in their diet (confounded by BCS since these horses/ponies were probably already recognized by owners/managers to be "easy keepers).
- Had received corticosteroids within 30 days (although presented with the caveat that the study included a low number of cases and controls that had received corticosteroids)
Tons of data collected by participating veterinarians all over the US and Canada made this study possible, which started as the group of authors meeting for a big brainstorming and study design session in Atlanta in 2010, many e-mail discussions, and a lot of hard work by Michelle Coleman of Texas A&M University, the lead author, and her thesis advisor during the study, Noah Cohen."

Let the laminitis data gathering begin! 
Ed Kane, dvm360, Apr 2012

Siciliano PD, Gill JC, Bowman MA
Effect of Sward Height on Pasture Nonstructural Carbohydrate Concentrations and Blood Glucose/Insulin Profiles in Grazing Horses
JEVS October 2017 vol 57, Pages 29–34

Highlights

• •Frequent mowing decreases pasture plant nonstructural carbohydrate concentration.
• •Horses grazing shorter sward height pasture have attenuated blood insulin response.
• •Maintaining shorter pasture sward height can potentially decrease laminitis risk.

AbstractSix mature stock-type geldings with maintenance only requirements were used in a randomized cross-over design to determine the effect of sward height on pasture plant nonstructural carbohydrate (NSC) concentrations and blood glucose and insulin concentrations. Horses were randomly assigned to one of two tall fescue (Lolium arundinaceum Schreb cv Max-Q, Pennington Seed, Madison, GA) grazing cells (0.37 ha) having two different sward heights for a period of 7 days: (1) short (approximately 15 cm; n = 3) or tall (between 30 and 40 cm; n = 3). After the first 7-day period, treatment groups were reversed by moving horses to ungrazed cells having similar characteristics to those used in the first 7 days, so that all horses receive all treatments resulting in six observations per treatment. Both short and tall grazing cells were mowed to a height of approximately 15 cm 32 days before the experiment starts. The short grazing cells were removed to approximately 15 cm at 11 days before the start of the first 7-day period and again 1 day before the start of each 7-day period. All horses had access to pasture for 10 h/d beginning at 8 AM and ending at 6 PM. Although not at pasture, all horses were individually housed in 3.7 × 12.2 m partially covered pens containing automatic water troughs and a crushed stone surface. Herbage mass (kg DM/ha) was determined by use of a falling plate meter for each pasture to ensure that both groups of horses had adequate dry matter to provide grazing for at least 7 days. On day 7 of each period, jugular venous blood samples were collected from each horse before being turned out to pasture, and then at 2, 4, 6, and 8 hours after turn-out. Pasture samples were also collected from each grazing cell at the same time blood samples were taken. Serum and plasma from blood samples were harvested and analyzed for insulin and glucose concentrations, respectively. Pasture samples were analyzed for water soluble carbohydrate (WSC), ethanol soluble carbohydrate (ESC), and starch. The sum of WSC and starch were used as an estimate of NSC. Area under the curve (AUC) and peak concentration were calculated for both plasma glucose (PPG) and serum insulin (PSI) concentration and were analyzed using analysis of variance for randomized cross-over designs. Pasture WSC, ESC, starch, and NSC concentrations were analyzed using analysis of variance for randomized complete block design. A P value of < .05 was considered significant. Mean pasture plant NSC, WSC, and ESC concentrations were lower (P < .001) in short as compared with tall. Pasture plant starch concentration was not different between treatments. Mean pregrazing plasma glucose concentrations, PPG concentrations, and plasma glucose AUC were not affected by treatment. Mean pregrazing serum insulin concentrations were not affected by treatment. Mean PSI and insulin AUC were greater (P < .01) when horses grazed tall, as compared with short. In conclusion, decreasing the sward height by mowing pasture decreased NSC, WSC, and ESC concentrations and subsequently decreased the postprandial insulin response of horses grazing the pasture. These findings may be important in developing strategies aimed at preventing insulin resistance in grazing horses.

See also

Regular pasture mowing has potential to reduce laminitis risk for horses, study finds - Horsetalk.co.nz July 2017

​Carslake HB, Pinchbeck GL, McGowan CM
Evaluation of a Chemiluminescent Immunoassay for Measurement of Equine Insulin
Journal of Veterinary Internal Medicine published online 26 January 2017

​Abstract
Background Many diagnostic tests for insulin dysregulation use reference intervals established with an insulin radioimmunoassay (RIA) that is no longer available. A chemiluminescent immunoassay (CLIA) is commonly used for the measurement of serum insulin concentration in clinical practice but requires further validation, especially at clinically relevant reference intervals.
Objectives To evaluate the CLIA for measurement of equine insulin and compare it to the previously validated, but now unavailable RIA.
Samples Equine serum samples (n = 78) from clinical and experimental studies.
Methods In this experimental study, performance of the CLIA was evaluated using standard variables, including comparison with the RIA. Continuous and binary outcomes were analyzed.
Results The CLIA showed good intra-assay (coefficient of variation [CV], 1.8–2.4%) and interassay (CV, 3–7.1%) precision. Acceptable recovery on dilution (100 ± 10%) was achieved only at dilutions <1:1. Recovery on addition was acceptable. Comparison of the CLIA and RIA showed strong positive correlation (r = 0.91–0.98), with fixed and proportional bias. At 3 diagnostic cutoffs, sensitivity of CLIA compared with RIA ranged from 67 to 100% and specificity from 96 to 100%.
Conclusions and Clinical Importance The CLIA is a highly repeatable assay which is suitable for within- and between-horse comparisons. Dilution of high concentration samples should be performed with charcoal-stripped serum (CSS) and at the lowest dilution factor possible. At concentrations commonly used for diagnosis of insulin dysregulation (≤100 μIU/mL), results from the CLIA tend to be lower than from the RIA and should be interpreted accordingly. Further standardization of equine insulin assays is required.

Smith S, Harris PA, Menzies-Gow NJ
Comparison of the in-feed glucose test and the oral sugar test
Equine Veterinary Journal published online 7 MAY 2015 (PubMed)

Abstract
REASONS FOR PERFORMING STUDY:The in-feed oral glucose test (OGT) and oral sugar test (OST) are advocated as field tests of insulin sensitivity in horses and ponies but have not been directly compared.
OBJECTIVES:To compare the insulin response to OGT and OST in 8 ponies and 5 horses of unknown insulin sensitivity.
STUDY DESIGN:Experimental, randomised crossover study.
METHODS:Animals were fasted for 8 h overnight before and throughout testing. They were fed 1 g/kg bwt glucose powder with chaff (OGT) or 0.15 ml/kg bwt corn syrup (Karo™ Light Syrup; OST) was administered per os in a randomised crossover study with 48 h between tests. Blood samples were obtained at 0, 30, 60, 75, 90, 120 and 180 min. The maximal insulin concentration (Cmaxi ), time to maximal insulin concentration (Tmaxi ) and area under the curve of insulin concentration over time (AUCi ) for the tests were compared using Student's paired t test. The effect of individual subject, horse or pony and test were analysed using a linear mixed model.
RESULTS:The OGT Cmaxi (mean ± s.d.; 154 ± 116 μiu/ml), Tmaxi (136 ± 52 min) and AUCi (15,308 ± 9886 μiu/ml/min) were significantly (P<0.05) greater compared with the OST Cmaxi (72 ± 55 μiu/ml), Tmaxi (63 ± 25 min) and AUCi (5980 ± 4151 μiu/ml/min). The Cmaxi , Tmaxi and AUCi varied significantly between individual subjects. The Tmaxi was significantly different between horses and ponies during OGT and OST. Using previously defined criteria of insulin dysregulation, OGT identified 7/13 animals as insulin resistant, whereas OST identified 5/13 animals as insulin resistant.
CONCLUSIONS:The OGT and OST showed agreement in identification of insulin dysregulation in 85% of equine subjects. Results of the OGT and OST are not comparable in all cases. Further work is required to establish which test more accurately diagnoses insulin dysregulation in horses and ponies.

Reisinger N, Schaumberger S, Nagl V, Hessenberger S, Schatzmayr G
Milk Thistle Extract and Silymarin Inhibit Lipopolysaccharide Induced Lamellar Separation of Hoof Explants in Vitro
Toxins (Basel). 2014 Oct; 6(10): 2962–2974. Published online 2014 Oct 6

Introduction

The paper states that "bacterial endotoxins have been suggested to contribute to the pathophysiology of laminitis", and in support cites:
Bailey SR, Adair HS, Reinemeyer CR, Morgan SJ, Brooks AC, Longhofer SL, Elliott J 
Plasma concentrations of endotoxin and platelet activation in the developmental stage of oligofructose-induced laminitis 
Vet Immunol Immunopathol. 2009 Jun 15;129(3-4):167-73. Epub 2008 Nov 7
Bailey's paper states "endotoxin (lipopolysaccharide; LPS)"..."does not cause laminitis when administered alone".  At the most, it seems "endotoxin may contribute in the initiation of the early inflammatory changes observed in experimental models of acute laminitis".

But more recent research has found that LPS administration does not cause laminitis:

Tadros EM, Frank N
Effects of continuous or intermittent lipopolysaccharide administration for 48 hours on the systemic inflammatory response in horses
Am J Vet Res. 2012 Sep;73(9):1394-402
"Horses (given LPS for 48 hours) developed LPS tolerance within approximately 24 hours after administration was started, and the method of LPS administration did not affect the magnitude or duration of systemic inflammation. Laminitis was not induced in horses".

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
Vet Immunol Immunopathol. 2012 Nov 15;150(1-2):90-100 Epub 2012 Sep 7
Horses were treated with LPS or saline, and then given oligofructose.  Pre-treatment with LPS made no difference to whether horses developed laminitis or not.

Tóth F, Frank N, Chameroy KA, Bostont RC
Effects of endotoxaemia and carbohydrate overload on glucose and insulin dynamics and the development of laminitis in horses
Equine Vet J. 2009 Dec;41(9):852-8
Horses treated with LPS had signs of systemic inflammation (which would be expected - LPS stimulates an inflammatory response), but none developed clinical laminitis.

For more examples see Lipopolysaccharides.

The paper then suggests that perfusing cut-off legs with LPS caused changes to the lamellae, citing:
Patan-Zugaj B, Gauff FC, Licka TF
Effects of the addition of endotoxin during perfusion of isolated forelimbs of equine cadavers
Am J Vet Res. 2012 Sep;73(9):1462-8
in which forelimbs from slaughtered horses were perfused with 80 ng LPS/l for 10 hours, and increased width and other changes were seen in the laminae.   However, does it follow that something that happens under unnatural circumstances in a dead leg would happen in a live horse with naturally occurring LPS levels (particularly given that Tadros and Frank 2012 above found that when horses were given LPS for 48 hours, they developed tolerance to LPS within 24 hours)?

The paper states "laminitis is an inflammation of the lamellar tissue".  This is only in SIRS laminitis - which is likely to make up no more than 10% of all cases of laminitis.  By far the majority of laminitis cases - thought to be around 90% - are endocrine, i.e. caused by EMS or PPID, and recent research has suggested that there is little inflammation involved in endocrine laminitis - see Inflammation.

It is suggested that "phytogenic substances with anti-inflammatory properties might have the potential to neutralize LPS in the gut".  But the research looks at hoof tissue, not the gut....

Discussion

Increased plasma endotoxin levels have been measured in horses following oligofructose administration: 

Bailey et al. 2009 horses given 10 g/kg BW (so 5 kg for a 500 kg horse!) oligofructose (presumably by nasogastric tube) had peak plasma LPS levels of 2.4 +/- 1.0 pg/ml 8 hours after OF administration, and 5/6 horses showed signs of clinical laminitis and histopathological changes in their lamellae.  "These data indicate that small quantities of endotoxin may move into the circulation from the large intestine after the sharp decrease in pH that occurs as a result of carbohydrate fermentation".

Sprouse RF, Garner HE, Green EM
Plasma endotoxin levels in horses subjected to carbohydrate induced laminitis
Equine Vet J. 1987 Jan;19(1):25-8
13/20 horses developed Obel grade 3 laminitis after carbohydrate overload, and of these, 11 had increases in plasma endotoxin from control levels of less than 0.1 ng/litre to values ranging from 2.4 to 81.53 ng/litre. 

Pretreatment with LPS increased the incidence of laminitis when horses were given oligofructose:
Toth et al. 2009 - 0/8 horses given LPS only developed laminitis; 2/8 horses given 5 g/kg BW (so 2.5 kg for a 500 kg horsre) oligofructose by nasogatric tube developed laminitis; 5/8 horses given LPS then oligofructose developed laminitis.

LPS administration alone has failed to induce laminitis -

but administration of LPS has affected behaviour, haematologic and coagulation values, increased heart reat and body temperature and caused decreased digital blood flow and laminar perfusion (and appeared to cause clinical signs of laminitis!):

Duncan SG, Meyers KM, Reed SM, Grant B
Alterations in coagulation and hemograms of horses given endotoxins for 24 hours via hepatic portal infusions
Am J Vet Res. 1985 Jun;46(6):1287-93
Horses given infusions of 1 µg/kg BW LPS into the hepatic portal vein per hour for 24 hours (12 mg LPS/500 kg horse) collapsed in the first hour (without an accompanying hypotension), had decreased neutrophils and increased circulating fibrinogen, and a shortening of the recalcification tests, 1-stage prothrombin time, and activated partial thromboplastin time.  All horses showed signs of hoof discomfort and "either stood with the 4 feet together beneath the body or continually shifted their weight from one front foot to the other. Hoof temperature decreased approximately 3 degrees (C) during this time and remained decreased for the duration of the experiment".

Ingle-Fehr JE, Baxter GM
Evaluation of digital and laminar blood flow in horses given a low dose of endotoxin
Am J Vet Res. 1998 Feb;59(2):192-6
6 healthy horses were given IV 0.1 µg/kg BW endotoxin (50 µg/500 kg horse).  Compared to controls, endotoxin treatment caused a significant decrease in digital blood flow, increases in heart rate and body temperature, and decreased laminar perfusion.

It is hypothesised that LPS is not able to induce laminitis on its own, but plays an important role in the development of laminitis.

Endotoxins (ex-vivo, i.e. infused into a dead leg) have a negative effect on the lamellar tissue.

There is some suggestion that after 24 hours, cells start to repair the damage induced by LPS.

Polymyxin B (PMB) is known to bind and neutralize endotoxins, and has been used on horses:

Morresey PR, Mackay RJ
Endotoxin-neutralizing activity of polymyxin B in blood after IV administration in horses
Am J Vet Res. 2006 Apr;67(4):642-7
5 healthy horses were given:
1. 1 mg of polymyxin B (PMB)/kg BW was given IV.
2.  1 mg of PMB/kg BW was given IV every 8 hours for 5 treatments. 
Conclusions: PMB given as multiple infusions to healthy horses did not accumulate in the vascular compartment and appeared safe.  Results support repeated IV use of 1 mg of polymyxin B/kg at 8-hour intervals as treatment for endotoxemia.

Barton MH, Parviainen A, Norton N
Polymyxin B protects horses against induced endotoxaemia in vivo
Equine Vet J. 2004 Jul;36(5):397-401
4 groups of 6 healthy horses received 20 ng endotoxin/kg BW IV plus one of:
5000 u PMB/kg BW IV 30 mins before endotoxin infusion; 
5000 u PMB/kg BW IV 30 mins after endotoxin infusion; 
1000 u PMB/kg BW IV 30 mins prior to endotoxin infusion; 
saline (controls).
Neutrophil count, serum tumour necrosis factor (TNF) activity, plasma thromboxane B2 concentration and urine GGT:creatinine ratio were measured.  
PMB treatment before or after endotoxin infusion significantly reduced fever, tachycardia and serum TNS, compared to controls.  Horses that received 5000 u PMB/kg BW IV 30 mins before endotoxin infusion had the best response.  
Conclusion: "PMB may be a safe and effective treatment of endotoxaemia, even when administered after onset. Although nephrotoxicity was not demonstrated with this model, caution should be exercised when using PMB in azotaemic patients".

Mild adverse side effects have been seen with PBD treatment:
MacKay et al 1999 - transient tachypnea, sweating and increased plasma thromboxane B2 concentration, but prior treatment with ketoprofen eliminated all PBD-induced signs.
Schwarz et al. 2013 - 6/18 horses being treated with 5000 iu polymyxin/kg BW IV every 8 hours for endotoxaemia showed a self-limiting weak ataxic gait between 24 and 36 hours after starting treatment.  Concurrent use of neostigmine may have potentiated PBD side effects.

J Appl Microbiol. 2014 Aug;117(2):329-39
Inhibition of fructan-fermenting equine faecal bacteria and Streptococcus bovis by hops (Humulus lupulus L.) β-acid
Harlow BE1, Lawrence LM, Kagan IA, Flythe MD

PubMed abstract:

"AIMS:The goals of this study were to determine if β-acid from hops (Humulus lupulus L.) could be used to control fructan fermentation by equine hindgut micro-organisms, and to verify the antimicrobial mode of action on Streptococcus bovis, which has been implicated in fructan fermentation, hindgut acidosis and pasture-associated laminitis (PAL) in the horse.

METHODS AND RESULTS:Suspensions of uncultivated equine faecal micro-organisms produced fermentation acids when inulin (model fructan) was the substrate, but β-acid (i.e. lupulone) concentrations ≥9 ppm inhibited lactate production and mitigated the decrease in pH. Inulin-fermenting Strep. bovis was isolated from the β-acid-free suspensions after enrichment with inulin. The isolates were sensitive to β-acid, which decreased the viable number of streptococci in faecal suspensions, as well as growth, lactate production and the intracellular potassium of Strep. bovis in pure culture.

CONCLUSIONS:These results are consistent with the hypothesis that hops β-acid prevented the growth of fructan-fermenting equine faecal bacteria, and that the mechanism of action was dissipation of the intracellular potassium of Strep. bovis.

SIGNIFICANCE AND IMPACT OF THE STUDY:Bacterial hindgut fermentation of grass fructans has been linked to PAL and other metabolic disorders in horses. Hops β-acid is a potential phytochemical intervention to decrease the growth of bacteria responsible for PAL."

TLS comment based on abstract:

This abstract should be read in conjunction with:

Journal of Equine Veterinary Science 33 (2013) 321-399
Effects of hops (Humulus lupulus L.) beta-acid extract on inulin fermentation by equine fecal microflora in vitro
BE Harlow, LM Lawrence, MD Flythe
Presented at the Equine Science Society Symposium 2013

We believe that the premiss of this research - "bacterial hindgut fermentation of grass fructans has been linked to PAL" - is flawed.  Bacterial hindgut fermentation of grass fructans has NOT been linked to Pasture Associated Laminitis (PAL).  

There are currently thought to be three types of laminitis:

SIRS
Supporting Limb
Endocrine

Endocrine laminitis probably accounts for ~90% of all cases of laminitis (Karikoski et al. 2011).  Pasture associated laminitis (PAL) is endocrine.  Sugars in the grass cause insulin to rise in some horses, i.e. horses with an underlying hormonal dysfunction - insulin resistance or hyperinsulinaemia.  As far as we know at the moment, fructans do not increase insulin levels (Borer et al. 2012), therefore they are very unlikely to be involved in causing PAL.  Horses with PAL have raised insulin, and/or symptoms of EMS.

In research,  huge amounts of inulin (a short-chain fructan which is not found in significant quantities in the horse's natural diet) have been pumped directly into a horse's stomach.  This has caused acidosis and led to SIRS laminitis.  Equivalent amounts of fructan cannot be eaten naturally, even by the greediest horse - and even if it could, it would be over 24 hours, not in 5 minutes.  With SIRS laminitis, the horse always has a significant primary illness, laminitis is secondary, and the horse will have changes in white blood cells and lactate, usually a raised temperature and usually diarrhoea.  These symptoms are not seen with PAL. 

So any research looking to reduce the fermentation of fructan to lactate and thereby reduce the incidence of acidosis has no relevance, as far as we know at the moment, for pasture associated laminitis.

It could have relevance for starch overload laminitis, which is SIRS laminitis. 

Going through the second abstract:

Brittany Harlow claims that "the ingestion of large quantities of fructan or other rapidly fermentable carbohydrates has been associated with the development of laminitis".  Starch yes, naturally ingested fructans, no. 

She claims that this can lead to proliferation of Gram-positive bacteria, leading to increased lactic acid production and acidosis.  Again starch, yes, naturally ingested fructan, no.  And that antibiotics e.g. Founderguard can be used to reduce this gut disturbance.  True - Founderguard may be useful when given in advance of  high amounts of starch being fed, but not grass - Founderguard has no beneficial action on reducing insulin. 

The research into the use of hops has basically come about because Founderguard, an antibiotic, cannot be used frequently and probably shouldn't be used at all (it's a preventative, not a cure) - we are all rightly worried about antibiotic resistance from the over-use of antibiotics.  So an alternative that doesn't raise concerns about antibiotic resistance might be a great idea. True - for horses that continue to be fed large amounts of cereal.  How about just not feeding them large amounts of cereal in the first place?

The study took 3 horses who were eating alfalfa hay and grass.  The abstract doesn’t give figures for the fructan or sugar content of the hay or grass.  Presumably the research was carried out in Kentucky, which is latitude 38 (compared to London 51).  Research suggests that C3 dominance changes to C4 at latitude 42-45, but the famous Kentucky blue grass is C3, and other research suggests quite a mix of C3 and C4 in Kentucky.  So there was probably less fructan in the grass than we'd see in the UK, but there will have been some (C3 stores excess carbs as fructan, C4 doesn't).  These horses were presumably healthy and managing to eat naturally occurring fructan with no problem, and no decrease in dung pH.

The researchers collected dung from these horses, separated bacteria from it and mixed the bacteria with inulin, then added hop extract to some of the samples and incubated them for 24 hours. 

Just how relevant is looking at the bacteria in dung compared to the bacteria inside the horse?  Is it likely that the "bad" lactic acid producing bacteria would be higher in dung than inside the horse?

The samples with only inulin added became more acidic and had higher lactic acid concentrations.  Adding hop extract at 180 ppm (mg/kg) or higher reduced this acidity.  We're told that after 21 hours the samples with 150  (I think this should say 180) ppm hop extract added had a pH of 6.2 (in the 0.1% inulin sample - without hop extract pH was 5.5) and 5.5 (in the 0.6% inulin sample - without hop extract pH was 3.7).  We're not told what the pH of the original dung was, and no control of bacteria with nothing (no inulin, no hop extract) added was used. 

Volatile Fatty Acid concentrations were also measured and were found to increase with increasing hop extract amounts in the 0.6% inulin sample.  This is quite interesting, because I have seen suggestions that fructans are only fermented to lactate, and not to VFAs as they should be (it seems obvious to me that horses are quite happily fermenting fructan to VFAs, given that millions of horses are happily eating grass, getting fat and not getting acidosis or laminitis).  VFA production figures aren't given, but the only/main substrate for fermentation is presumably the inulin, so this suggests that inulin is fermented by bacteria in/from the horse's gut to VFAs.  Treatment with hop extract increased VFA production and reduced lactate production.

This suggests that hop extract could reduce lactic acid producing bacteria without compromising VFA producing bacteria.  So this may be useful research for the very few cases of SIRS laminitis caused by planned cereal overload - but there is nothing to suggest that it can help pasture associated laminitis cases.

I haven't read the full paper - if anyone has, I'd be interested in your comments.


See Do fructans cause laminitis?

Also, have a look at this review of the paper by Kathleen, Director and Research Advisor of the ECIR group in December 2014 - What's the harm.  Why associations should be questioned.

References:

Borer KE, Bailey SR, Menzies-Gow NJ, Harris PA, Elliott J
Effect of feeding glucose, fructose, and inulin on blood glucose and insulin concentrations in normal ponies and those predisposed to laminitis
J Anim Sci. 2012 May 14 [Epub ahead of print]

Karikoski NP, Horn I, McGowan TW, McGowan CM
The prevalence of endocrinopathic laminitis among horses presented for laminitis at a first-opinion/referral equine hospital.
Domest Anim Endocrinol. 2011 Jun 7 

Equine Vet J. 2014 Jul 4
The impact of prolonged hyperinsulinaemia on glucose transport in equine skeletal muscle and digital lamellae
de Laat MA, Clement CK, Sillence MN, McGowan CM, Pollitt CC, Lacombe VA

PubMed Abstract
"REASONS FOR PERFORMING STUDY:An increased incidence of metabolic disease in horses has led to heightened recognition of the pathological consequences of insulin resistance (IR). Laminitis, failure of the weight-bearing digital lamellae, is an important consequence. Altered trafficking of specialised glucose transporters (GLUTs) responsible for glucose uptake, are central to the dysregulation of glucose metabolism and may play a role in laminitis pathophysiology.

OBJECTIVES:We hypothesised that prolonged hyperinsulinaemia alters the regulation of glucose transport in insulin-sensitive tissue and digital lamellae. Our objectives were to compare the relative protein expression of major GLUT isoforms in striated muscle and digital lamellae in healthy horses and during hyperinsulinaemia.

STUDY DESIGN:Randomised, controlled study.

METHODS:Prolonged hyperinsulinaemia and lamellar damage were induced by a prolonged-euglycaemic hyperinsulinaemic clamp (p-EHC) or a prolonged-glucose infusion (p-GI) and results were compared to electrolyte-treated controls. GLUT protein expression was examined with immunoblotting.

RESULTS:Lamellar tissue contained more GLUT1 protein than skeletal muscle (p = 0.002) and less GLUT4 than the heart (p = 0.037). During marked hyperinsulinaemia and acute laminitis (induced by the p-EHC), GLUT1 protein expression was decreased in skeletal muscle (p = 0.029) but unchanged in the lamellae, while novel GLUTs (8; 12) were increased in the lamellae (p = 0.03), but not skeletal muscle. However, moderate hyperinsulinaemia and subclinical laminitis (induced by the p-GI) did not cause differential GLUT protein expression in the lamellae vs. control horses.

CONCLUSIONS:The results suggest that lamellar tissue functions independently of insulin and that IR may not be an essential component of laminitis aetiology. Marked differences in GLUT expression exist between insulin-sensitive and insulin-independent tissues during metabolic dysfunction in horses. The different expression profiles of novel GLUTs during acute and subclinical laminitis may be important to disease pathophysiology and require further investigation."

Comment based on abstract:

This research should be read in conjunction with

de Laat M, Sillence M, McGowan C, Pollitt C 
Insulin-Induced Laminitis - An investigation of the disease mechanism in horses
RIRDC Dec 2011
Chapter 5.  Glucose uptake in the hoof is largely facilitated by insulin-independent GLUT-1 glucose transporters.

and

Asplin KE, Curlewis JD, McGowan CM, Pollitt CC, Sillence MN
Glucose transport in the equine hoof
Equine vet. J. (2011) 43 (2) 196-201