Aspects of studies on the pathogenesis of equine laminitis.

This article explores the potential factors leading to laminitis in horses, reviewing existing evidence and suggesting new research directions. The article covers research into systemic triggers of laminitis, such as isolated histamine and endotoxin from E. coli, as well as theories of the pathogenesis of laminitis, focusing on the potential role of blood flow alteration in the hoof and its possible connection with keratinocyte (epidermal cell) behavior.

Exploring Triggers of Laminitis

• The article starts by discussing potential triggers of laminitis in horses. Histamine and endotoxin from E. coli have been isolated from the intestinal contents of horses suffering from laminitis, providing a possible clue to the disease’s onset. These agents, when infused intravenously, were found to produce some of the systemic symptoms associated with laminitis.
• However, the hoof symptoms which are characteristic for laminitis did not appear after this infusion, raising doubts about whether these agents alone could induce laminitis.

Ischaemia Hypothesis for Laminitis

• One theory about the onset of laminitis involves ischaemia (restricted blood supply) in the laminar region of the hoof. Various studies using angiographic and scintigraphic techniques found reduced blood perfusion in the laminar region during laminitis.
• Contrarily, research using direct blood flow measurement found increased blood flow in the hooves during laminitis. This discrepancy could be due to a redistribution of blood flow in the foot, where blood mostly flows through low-resistance arteriovenous anastomoses, leading to reduced flow in capillaries and resulting in ischaemia.

Understanding Circulation in Laminitis

• A study by Trout et al. found a significant increase in blood flow through the laminar region in cases of experimental laminitis, strengthening the theory of altered blood flow during laminitis.
• However, it remains unknown whether the increased blood flow is due to elevated capillary flow, arteriovenous shunt flow, or a combination of both. The relative magnitudes of capillary and arteriovenous anastomoses (AVA) flow have yet to be conclusively established.

New Approaches to Understanding Laminitis

• Epidermal changes observed in a horse with post-surgical laminitis gave clues to a new potential research approach. These changes indicate inhibited differentiation of epidermal cells, which has been observed in laminitis-related conditions before.
• Research into substances that inhibit differentiation of cells shows that these can result in changes similar to those found in horses suffering from laminitis. Furthermore, substances such as cortisone and certain bacterial toxins, known to inhibit cell differentiation, are relevant in cases of laminitis, with cortisone-related laminitis being a well-known occurrence in treatments involving corticosteroids.
• Also, cholera toxin, which exhibits potent inhibition on keratinocyte differentiation, can have implications in laminitis research due to its similarity, in terms of biochemical effects, with the heat-labile enterotoxin of E. coli. As some research shows a connection between E. coli and laminitis, it could be valuable to investigate the effects of the enterotoxin of E. Coli on cultured hoof keratinocytes.

Future Directions for Laminitis Research

• The discussion concludes by suggesting that if hoof keratinocytes are shown to react to differentiation-inhibiting agents similarly to other types of keratinocytes, this could significantly advance our understanding of laminitis.
• The study implies that laminitis may result from complex interactions between various factors that collectively lead to intemperate growth and consequent suppression of differentiation of hoof keratinocytes.
• Further studies utilizing cultured hoof keratinocytes might be beneficial in decoding this multiplex process.