Rapid Death in Severe Gut Ischemia is Prevented By Parasympathetic Blockade

Abstract

Splanchnic arterial occlusion raises blood pressure (BP) in rats initially but within hours, even without reperfusion, BP falls irreversibly. Fatal pressure drops occur either over hours (slow) or in just minutes (fast). The fast BP drops occur without significant reduction of pulse pressure or pulse rate suggesting death is from neurogenic shock (i.e. dilation of peripheral blood vessels resulting in BP loss despite maintenance of cardiac contractility). Fast fatal pressure drops (FFPDs) occur more frequently and earlier if the rat is treated with intramuscular xylazine and glucose in the intestinal lumen, both stimulators of the parasympathetic nervous system (PNS). Thus we hypothesized parasympathetic inhibition by glycopyrrolate, a muscarinic anticholinergic, in intestinal ischemia could reduce incidence of rapid death. The results show that glycopyrrolate (1 mg/kg) significantly delayed onset of the fatal pressure drop (115±31 vs. 71±34 min post‐occlusion) and completely prevented FFPDs (0 of 6 vs. 5 of 8 animals with a fast death without glycopyrrolate), but not the slow form of pressure reduction. These results suggest that in severe intestinal ischemia, parasympathetic blockade prevents rapid pressure reductions, an observation that is consistent with a similar protection seen after vagotomy. Support: HL 67825, 76180, GM85072 and an unrestricted educational gift from Leading Ventures.