Ischemia in equine intestine – mechanisms of injury and methods of treatment

Abstract

SummaryThe importance of reperfusion injury in equine intestine is controversial and unclear. Large colon volvulus and small intestinal strangulation are the most devastating causes of intestinal ischemia in horses and result in severe mucosal damage, barrier dysfunction, endotoxic shock and death. Although essential for tissue recovery, reperfusion after these types of ischemia could exacerbate intestinal injury. Responses to ischemia and reperfusion (I/R) involve a series of synchronized biochemical, cellular and structural changes characterized by generation of reactive oxygen metabolites, activation of immune cells, and epithelial cell degeneration and death. The intensity of neutrophil activation and influx is central to the process of reperfusion injury and the associated inflammatory events. The classic paradigm of reperfusion injury is best displayed after the segmental hypoperfusion or low-flow ischemia model, in which arterial inflow is adjusted to 20% of normal baseline flow, and then allowed to return to normal or greater values during reperfusion. In such cases, injury during the ischemic phase is mild, compared with the reperfusion injury that follows. Although there is some evidence of reperfusion injury in equine colon and jejunum after low-flow ischemia, attempts to ameliorate this by pharmacologic means have met with only moderate success. A multimodal approach, using solutions designed to improve survival in transplanted organs, seems to hold the greatest promise, although these have not been embraced in the clinical setting. Expense and difficulties in delivery are the two most serious limitations. Recent studies to assess the effect of colonic I/R on equine pelvic flexure involved a complete ischemia model that was similar to the clinical lesion, and for periods of 1 to 2 hours of ischemia followed by 30 minutes, 4 hours, or 18 hours of reperfusion. Ischemia caused degeneration and detachment of epithelial cells, early apoptosis, and opening of tight junctions (TJs), all of which decreased transepithelial resistance (TER) and increased mannitol flux when the tissues were studied in vitro. Autophagy was a prominent feature in epithelial cells after 1 hour of ischemia. Reperfusion was characterized by apoptosis, epithelial regeneration, and closure of TJs with improved TER and reduced mannitol leakage. Neutrophils infiltrated colonic mucosa during reperfusion, and macrophages, mast cells and eosinophils were activated during I/R. Equine colonic mucosa subjected to ischemia can repair rapidly and regain barrier integrity during reperfusion, despite intense mucosal inflammation. Recently, attention has focused on inflammation induced by intestinal handling and on remote organ responses to intestinal injury, both of which could be highly relevent to postoperative management of horses that undergo colic surgery. The use of lidocaine in a continuous rate infusion is a popular approach to ameliorate the intestinal inflammatory response after colic surgery, although there is no evidence that it has a...

Fifty years of colic surgery

“…The potential for reperfusion injury to exacerbate inflammation in horses after colic surgery has led to studies on a large number of different treatments; however, consistent evidence of a beneficial response is lacking . Carolina Rinse solution contains antioxidants and was designed to support organ viability for transplantation.…”