Endothelial Dysfunction as an Early Critical Event in Ischemia and Shock

Abstract

Splanchnic artery occlusion (SAO) followed by reperfusion (R) of the ischemic splanchnic visceral organs results in precipitous decline in systemic blood pressure, leading to a circulatory shock state [1]. SAO + R shock is a very severe form of shock with a characteristic high mortality rate (i.e., 80%–95%). The pathogenesis of SAO + R shock is complex and involves multiple mechanisms including (a) capillary leakage and hypovolemia, (b) loss of vascular control mechanisms (e.g., tendency towards poor splanchnic perfusion, vasospasm), and (c) depression of myocardial contractility [2]. Recently, neutrophils have been implicated in contributing to SAO + R shock [3, 4]. Neutrophil accumulation in tissues may lead to the release of a variety of humoral mediators of shock including (a) oxygen derived free radicals (e.g., superoxide radical), (b) cytokines (e.g., tumor necrosis factor, TNF), and (c) proteolytic enzymes (e.g., elastase). Additionally neutrophils may accumulate in small blood vessels and physically obstruct blood flow there, thus contributing to the perpetuation of the ischemic state [5]. Similar effects occur during myocardial ischemia and reperfusion (MI + R) [5, 6] except that a lethal form of shock does not develop.