title: Severe intestinal ischemia can trigger cardiovascular collapse and sudden death via a parasympathetic mechanism.
abstract: Hemorrhagic shock and splanchnic arterial occlusion (SAO) followed by reperfusion are associated with high mortality. However, rapid cardiovascular failure and death may also occur before reperfusion in hemorrhagic shock and SAO. We show in a rat SAO model that, upon gut ischemia, mean arterial blood pressure transiently elevates and then drops fatally in one of two time courses: (i) gradually over ∼1 to 3 h or (ii) rapidly (often by >80 mmHg) over a period of 1 to 6 min. We hypothesize that fast fatal pressure drops (FFPDs) are due to failure of autonomic nervous system control. To test this, we treated rats with Glucose (10%) in the small intestinal lumen and intramuscularly administered xylazine to activate the parasympathetic nervous system or with a muscarinic anticholinergic (glycopyrrolate) or by total subdiaphragmatic vagotomy to attenuate parasympathetic nervous system activity. We also tested nafamostat mesilate (ANGD [6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfonate]), a protease inhibitor efficacious in preventing blood pressure loss in SAO with reperfusion, in the intestinal lumen. Fifty percent of animals receiving xylazine and Glucose died by FFPD (vs. 33% with neither, not statistically significant). Total subdiaphragmatic vagotomy or glycopyrrolate treatment significantly reduced the incidence to 0% (P < 0.008), although slow fatal pressure drops still occurred. ANGD did not prevent FFPDs, but delayed onset of slow fatal pressure drops (P < 0.013). These results suggest that gut ischemia can cause sudden death via an autonomic nervous system mechanism and that SAO with Glucose and xylazine may serve as a useful model for the study of neurogenic shock or autonomic dysregulation associated with sudden death.
authors: Department of Bioengineering, The Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA. apenn@bioeng.ucsd.edu
authors: Alexander H
authors: AH
authors: Penn
authors: Geert W
authors: GW
authors: Schmid-Schönbein
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