Gut and Liver

Open Access
Publisher Website
Google Scholar
Abstract
SEVERE HEMORRHAGIC shock is characterized by circulatory failure with hypotension and loss of vascular reactivity to adrenergic agonists. This leads to tissue damage, multiple organ failure (MOF), and finally death. However, the precise mechanism underlying cardiovascular dysfunction and the subsequent MOF remains unknown. Based on a variety of studies, overproduction of nitric oxide (NO) caused by activation of the L-arginine–NO synthase (NOS) pathway is involved in the sequence of events leading to MOF after hemorrhagic shock.1-5 Cuzzocrea et al4 suggest that overproduction of NO may be responsible for the occurrence of MOF after zymosan-induced peritonitis. Two types of NOS have been characterized. Under physiologic conditions, NO release from vascular endothelial cells (through constitutive NOS [cNOS]) regulates vascular tone, blood pressure, and tissue perfusion.6 After various pathophysiological conditions such as prolonged hemorrhage and sepsis, however, an inducible form of NOS (iNOS) may produce a large amount of NO, which has been implicated in producing cell and organ dysfunctions seen in those circumstances.4,7-9 It has been shown that tumor necrosis factor and interleukin 1 (IL-1) can stimulate iNOS expression, leading to an overproduction of NO in vascular smooth muscle cells, endothelial cells, and macrophages in vitro10-12 and in various organs in vivo.1 Moreover, proinflammatory cytokines such as tumor necrosis factor, IL-1, and IL-6 were elevated after trauma-hemorrhage as early as 45 minutes after the induction of hypotension.13 These cytokines are involved in pathophysiological responses after trauma-hemorrhage, possibly through up-regulation of NO production. Although inadequate perfusion has been postulated to produce cell and organ dysfunctions and although splanchnic circulation is thought to be at particularly high risk because of its tendency to be selectively hypoperfused under the shock state, it remains unknown whether altered tissue perfusion after hemorrhage has any effects on NO production. The aim of this study was to determine whether NO production is up-regulated after trauma-hemorrhage and resuscitation and, if so, which organs contribute to the increased NO production.