Roles of Nitric Oxide in Surgical Infection and Sepsis

Abstract

Recent advances in nitric oxide (NO) research have begun to elucidate the roles of NO in sepsis and infection. Although adequate levels of NO production are necessary to preserve perfusion and carry out cytoprotective functions in sepsis, overproduction appears to contribute to hemodynamic instability and tissue damage. These observations have led to the development of strategies to inhibit NO synthesis or scavenge excess NO in patients with septic shock. Local expression of the inducible NO synthase also has antimicrobial functions. The combination of NO with superoxide forms peroxynitrite which participates in bacterial killing in the peritoneal cavity. The capacity of red blood cells and hemoglobin to remove NO most likely accounts for the adjuvant effect of blood in peritonitis. This review will summarize the pathobiology of NO in surgical sepsis and infection.

A Novel Inhibitory Peptide of Toll-Like Receptor Signaling Limits Lipopolysaccharide-Induced Production of Inflammatory Mediators and Enhances Survival in Mice

“…The liver is believed to integrate the inflammatory response during gram-negative infections through both the clearance of microbes and their products and through the production of inflammatory mediators and acute-phase proteins (15,16). It has been shown that the liver is the main organ involved in the clearance of LPS from the bloodstream, and it also plays a critical role in the identification and processing of LPS (17,18).…”

In Silico Models of Acute Inflammation in Animals

“…The induced damage, which we define in much the same way as inflammation-promoting Balarm/ danger[ signals derived from stressed or dysfunctional cells (39), can incite more inflammation by activating macrophages and neutrophils (40). However, NO can also protect tissue from damage induced by shock (41 Y43), although overproduction of this free radical causes hypotension (37). Proinflammatory cytokines also reduce the expression of endothelial nitric oxide synthase (eNOS), thereby increasing tissue dysfunction (44).…”

Suppression of lipopolysaccharide-induced nitric oxide synthase expression by platelet-activating factor receptor antagonists in the rat liver and cultured rat kupffer cells

“…Considerable evidence has shown that overproduction of NO by hepatic parenchymal and nonparenchymal cells during endotoxemic episodes contributes to liver tissue damage and impaired function. 8,11,[40][41][42] Thus, a reduction in the capacity of hepatic cells to generate NO derived from iNOS during endotoxemia should be hepatoprotective. Studies using iNOS knockout mice have revealed conflicting results.…”