Pathogenesis of nonocclusive ischemic colitis

The nonocclusive component of ischemic colitis in anesthetized pigs was mimicked using cardiogenic shock produced by pericardial tamponade. Increases in pericardial pressure produced decreases in arterial pressure (PA) and cardiac output (CO), with corresponding rises in total peripheral resistance (i.e., cardiogenic shock). This was associated with marked reductions in blood flow through the inferior mesenteric artery (IMA), due primarily to disproportionate increases in IMA vascular resistance. Levels of plasma renin activity correlated closely with these changes in mesenteric hemodynamics. Confirmed, total alpha adrenergic blockade with phenoxybenzamine failed to block this selective mesenteric vasoconstriction, while ablation of the renin-angiotensin axis with captopril completely abolished it, thereby ameliorating the colonic ischemia. Central intravenous infusions of pathophysiologic levels of angiotensin II, without tamponade, mimicked the response to shock seen with tamponade alone. In an additional group of pigs, 4 hours of sustained shock (tamponade) followed by 2 hours of normotension (release of tamponade and resuscitation) produced lesions characteristic of ischemic colitis, including full-thickness mucosal ulceration. Such lesions were ameliorated significantly in pigs in which the renin-angiotensin system had been ablated by bilateral nephrectomy. Nonocclusive ischemic colitis appears to be mediated primarily by a remarkable sensitivity of the colonic vasculature to the renin-angiotensin axis.