Nitric oxide donors improve gut function after prolonged hypothermic ischemia.

Abstract

The objective of this study was to determine whether the nitric oxide (NO) donors, spermine NO and 3-morpholinosydonimine-N-ethyl-carbamide (SIN1), alter the mucosal and microvascular responses of the feline small intestine to 6 hr of hypothermic ischemia and 2 hr of normothermic reperfusion. Intestinal mucosal permeability was monitored using the blood-to-lumen clearance of 51Cr-EDTA. Lymph flow and lymphatic protein clearance estimates were used to assess intestinal microvascular fluid filtration and vascular protein leakage, respectively. Spermine NO (0.1 mmol/L) or SIN1 (0.5 mmol/L) was added to the luminal perfusate during the entire reperfusion period. Both NO donors were effective in attenuating the increased mucosal permeability to 51Cr-EDTA and the depressed net water absorption, relative to untreated intestinal preparations exposed to the same protocol. Intestinal lymph flow, lymphatic protein clearance, and capillary hydrostatic pressure were increased by a greater extent in preparations treated with spermine NO. These findings suggest that NO donors may improve mucosal function in intestinal allografts subjected to prolonged hypothermic ischemia. This protective effect on mucosal epithelium appears to be unrelated to an action of the NO donors on the microvasculature.