Pathophysiologic and Therapeutic Implications of Endothelin-1

Endotoxemia and the roll of ET-1 in acute Laminitis

"Although administration of a low-dose of endotoxin to horses causes a significant decrease in laminar perfusion and digital blood flow, there have been no repeatable models of endotoxemia that consistently induces acute laminitis. However, diseases that are often complicated by laminitis are accompanied by endotoxemia (intestinal strangulating obstruction, anterior enteritis, enterocolitis, pleuropneumonia, and metritis). In a study in our laboratory, we demonstrated a significant decrease in digital arterial blood flow from 30 min to 2 h after administration of a low dose (35 ng/kg over 30 min) of endotoxin to conscious horses. There was a concomitant decrease in digital arterial blood pressure from 30 min to 1.5 h after endotoxin infusion. These digital hemodynamic effects were accompanied by a significant increase in cephalic venous plasma ET-1 concentrations. These findings suggest that perhaps endotoxin does play a role in initiation of the early hemodynamic alterations in laminitis, and that this may be at least partly mediated through increased synthesis and release of ET-1."

Authors: Susan C. Eades, DVM, PhD; Ashley M. S. Holm, DVM; and Rustin M. Moore, DVM, PhD