Nitric oxide administration restores the hepatic artery buffer response during porcine endotoxemia

The hepatic artery buffer response, which is lost during endotoxemia, plays a central role in the autoregulation of liver perfusion. A temporarily decreased synthesis of nitric oxide during early endotoxemia might be responsible for this dysfunction; hence exogenous administration of nitric oxide could reestablish the autoregulation of hepatic blood flow and help prevent hepatic damage later in septic shock. Fifteen pigs were treated with lipopolysaccharide +/- the nitric oxide donor nitroprusside-sodium via the portal vein. Hemodynamics were measured, and serum chemistry and liver biopsies for nitric oxide synthase expression were obtained. Lipopolysaccharide decreased arterial liver perfusion after 5 hours by 38% (p = .012), which was reversed by addition of nitroprusside (8%). Administration of nitroprusside preserved an increase of 28% in hepatic arterial upon portal vein flow reduction (p < .001). Nitroprusside maintained mRNA levels of constitutive nitric oxide synthase in liver tissue which were decreased by lipopolysaccharide (p = .026 vs. p = .114) and tempered the burst in inducible nitric oxide synthase expression at t = 3 hours. The early administration of the nitric oxide donor sodium nitroprusside during endotoxemia is able to reestablish the autoregulatory response of the hepatic artery following reduction of hepatic blood flow. This beneficial effect might help to prevent subsequent hepatic damage in the course of abdominal sepsis.