Expression of endothelin in equine laminitis.

Biosynthesis of endothelin-1 (ET-1), the most potent endogenous vasoconstrictor yet identified, is increased following myocardial infarction (MI) in man. Pathological events which occur in the connective tissues of the equine hoof during laminitis are similar in some respects, to changes occurring in the myocardial connective tissues following MI in man. The objective of this study was to determine whether ET-1 expression in connective tissues obtained from the hoof of laminitic horses is increased compared with tissues obtained from healthy horses. Expression of ET-1 in connective tissues of the equine hoof was measured following tissue extraction from 3 groups of horses: horses in which acute laminitis had been induced by the administration of starch; chronically foundered horses; nonlaminitic horses. The concentration of ET-1 in laminar connective tissues obtained from all laminitic horses (1573.0 +/- 392.8 pg/g of tissue; n = 10) was increased when compared with tissues obtained from nonlaminitic horses (392.5 +/- 117.4 pg/g of tissue; n = 5) (P<0.05). The concentration of ET-1 in laminar connective tissues obtained from the experimentally induced, acute laminitic horses (1043.6 +/- 254.4 pg/g of tissue; n = 7) and from the spontaneously affected, chronic laminitic horses (2808.3 +/- 878.6 pg/g of tissue; n = 3) was increased compared with the control group (P<0.05, P<0.01, respectively). The concentration of ET-1 in laminar connective tissues obtained from the chronic laminitic horses was greater than that of the experimentally induced, acute laminitic group (P<0.05). It is suggested that the data provide a strong argument that increased ET-1 expression in the connective tissues of the equine hoof represent a potentially important and hitherto unrecognised component of the pathophysiology of equine laminitis. Further studies are needed to determine whether inhibitors of ET-1 converting enzyme or antagonists of ET-1 receptors might be useful in the treatment and prevention of laminitis in horses.     

Glucocorticoid therapy and the risk of equine laminitis

Although glucocorticoids have been used successfully for the treatment of noninfectious inflammatory diseases of horses for more than 35 years, their use has been attended by a fear of the induction of laminitis. This paper reviews the evidence for this fear and the possible mechanisms whereby glucocorticoids could participate in laminitis induction. Although the association of laminitis with elevated serum cortisol in pituitary pars intermedia dysfunction suggests that chronic exposure to glucocorticoids may be part of laminitis pathogenesis, review of published reports and databases suggests that glucocorticoid‐induced laminitis is a relatively rare occurrence. However, several of the actions of glucocorticoids are similar to those known to be involved in laminitis pathogenesis. Glucocorticoid administration can induce insulin resistance, lead to vascular dysfunction that potentiates vasoconstriction, and interfere with keratinocyte proliferation and differentiation as well as matrix integrity, all mechanisms that could possibly induce laminitis. Drug formulation, dose and route of administration, and the systemic and hoof disease history of the horse must all be considered when assessing laminitis risk during glucocorticoid treatment. Generally, local glucocorticoid administration presents little risk as does systemic treatment of recurrent airway obstruction without concurrent disease. Caution should be used however in horses that are overweight and/or insulin resistant, or have had a recent bout of acute laminitis of alimentary or endotoxic origin. Overall, however, the risk of laminitis after glucocorticoid treatment, especially local use, is acceptable compared to the many benefits of these drugs.     

The diagnosis of equine insulin dysregulation

Insulin dysregulation is the hallmark of equine metabolic syndrome and has received attention because of its direct association with laminitis. In the absence of an adequate treatment for laminitis, a focus on prophylaxis is needed, making early detection of individuals at risk of developing laminitis one of the main challenges in equine endocrinology. Recent studies have shown that insulin dysregulation goes beyond tissue insulin resistance and it is now demonstrated that the equine enteroinsular axis plays a major role in insulin secretion and equine hyperinsulinaemia. In this review, we discuss the different tests currently available to diagnose insulin dysregulation in horses: the ones investigating tissue insulin resistance and those investigating the enteroinsular axis, detailing their goals, practicalities and limitations. This review supports the contention that the diagnosis of equine insulin dysregulation should now be based on the investigation of both tissue insulin resistance and the equine enteroinsular axis. Regardless of the tests used many factors of variation, such as breed, diet, fasting state or season, have been identified and could potentially confound the results of a specific test. Therefore, careful interpretation of the results of a given test in each individual situation is required to optimise the detection of horses at risk of laminitis.     

Short‐term incubation of equine laminar veins with cortisol and insulin alters contractility in vitro: possible implications for the pathogenesis of equine laminitis

This study investigated the effects of cortisol and insulin, hormones that affect both glycaemic status and vascular function, on the in vitro contractility of isolated healthy equine small laminar veins. Small veins (150–500 μm) draining the digital laminae from healthy horses or ponies were investigated by wire myography. Concentration response curves were constructed for noradrenaline (NA), phenylephrine (PE), endothelin‐1 (ET‐1) and 5‐hydroxytryptamine (5‐HT) in the presence of either cortisol (10^?6 m ) or insulin (1000 μIU/mL). Cortisol significantly increased the maximum contractility of laminar veins to the vasoconstrictors NA and 5‐HT but decreased the maximal contraction to ET‐1. Insulin decreased the contractility of vessels to PE and ET‐1. It is possible that short‐term cortisol excess could enhance venoconstrictor responses to 5‐HT and NA in laminar veins in vivo, thereby predisposing to laminitis. Additionally, a reduction in the ability of insulin to counteract alpha‐adrenoreceptor and ET‐1‐mediated contraction, likely to occur in subjects with insulin resistance, may further exacerbate venoconstriction in animals prone to laminitis. These mechanisms may also predispose horses with disorders such as equine Cushing's disease and equine metabolic syndrome to laminitis.     

Bovine laminitis: clinical aspects, pathology and pathogenesis with reference to acute equine laminitis

This review deals with the features of clinical and subclinical laminitis in cattle. Prominent clinical signs of acute laminitis are a tender gait and arched back. The sole horn reveals red and yellowish discolourations within five days. In subacute and chronic cases clinical signs are less severe. In chronic laminitis the shape of the claws is altered. Laminitis is frequently followed by sole ulceration and white zone lesions. Blood tests showed no significant changes for laminitic animals. Arteriographic studies of claws affected by laminitis indicated that blood vessels had narrowed lumens. Gross pathology revealed congestion of the corium and rotation of the distal phalanx. Histopathologic studies indicate that laminitis is associated with changes of the vasculature. Peripartum management and nutrition are important factors in its aetiology. It is hypothesised that laminitis is evoked by disturbed digital circulation. In the pathogenesis of acute laminitis three factors are considered important: the occurrence of thrombosis, haemodynamic aspects of the corium, and endotoxins which trigger these pathologic events.     

The prevalence of endocrinopathic laminitis among horses presented for laminitis at a first-opinion/referral equine hospital

Endocrinopathic causes of laminitis may be a common underlying causative pathogenesis in first-opinion or field cases presenting with laminitis, as opposed to laminitis produced in inflammatory research models. This study aimed to determine whether evidence of an underlying endocrinopathy was present in horses presented for laminitis to a first-opinion/referral veterinary teaching hospital. A second aim was to compare the signalment of horses and ponies with laminitis with the equine hospital population during the same period. All horses presenting for laminitis at Helsinki University Equine Teaching Hospital, Finland, over a 16-month period were examined for an underlying endocrinopathy. Horses presenting for laminitis were compared with the hospitalized population over the same period. There were 36 horses presented for laminitis, and evidence of endocrinopathy was present in 89%. Of the horses showing an underlying endocrinopathy, one-third had a diagnosis of pituitary pars intermedia dysfunction, and two-thirds showed basal hyperinsulinemia indicative of insulin resistance, without evidence of hirsutism. Phenotypic indicators of obesity were present in 95% of horses with basal hyperinsulinemia without hirsutism. Compared with the hospital population during the same period, horses with laminitis associated with an underlying endocrinopathy were significantly older and more likely to be pony breeds. Our data support that endocrine testing should be performed on all cases of laminitis that do not have a clear inflammatory or gastrointestinal origin.     

Ultrastructural study of the equine cecum during onset of laminitis

The morphologic and pathologic changes which occurred within the cecal mucosa of 4 horses during the onset of laminitis were determined from cecal biopsy materials obtained via a cecal fistula; the laminitis was induced with carbohydrate overload. The cecal epithelial mucosa specimens were obtained at 0 (base line), 24, 32, 48, and 72 hours after horses were given carbohydrate overload, and these were fixed and subsequently photographed. Changes in the cecal epithelium were examined by transmission electron and scanning electron microscopies. These histopathologic changes indicated that the mucosal barrier was substantially damaged by the carbohydrate overload.     

Factors involved in the prognosis of equine laminitis in the UK.

The significance of clinical and radiological parameters as prognostic indicators for laminitis, 'founder' and 'sinking syndrome' was studied using case records of 216 horses and ponies. Five animals were destroyed without treatment and were not included in the results of the study. One hundred and sixty-two (77%) animals returned to athletic soundness; 7 animals (3%) did not regain full athletic function, 42 animals (20%) died or were destroyed. Cases were assigned to 4 groups on the basis of initial clinical examination alone. These groups were laminitis, acute founder, 'sinker' and chronic founder. This grouping was found in itself to be the most important prognostic parameter which was studied. Stepwise regression analysis of the data from animals by group indicated that the radiological measurement of founder distance, was the most significant radiological prognostic measurement for acute founder cases. Less significant prognostic parameters were the severity of lameness, rotation angles, the presence of solar prolapse, and the number of feet affected. The height of the animal at the withers was not significantly related to outcome. The prognosis for horses was not significantly different from that for ponies.