Effects of Nitric Oxide Synthase Inhibition on Regional Blood Flow in a Porcine Model of Endotoxic Shock

Abstract

The results of early studies suggest that nitric oxide (NO) synthesis inhibition may be therapeutic in sepsis, but recent data indicate that NO inhibition may be harmful. This study investigates the effects of NO synthesis inhibition with N-nitro-L-arginine methyl ester (NAME) on regional blood flow following endotoxemia. Anesthetized, instrumented swine were randomly divided into four groups. Controls received normal saline resuscitation (NSR) at 1 cc/kg/min beginning at T0. The lipopolysaccharide group (LPS) received NSR and Escherichia coli LPS, 200 micrograms/kg at T0. The LPS+NAME group received NSR and LPS at T0, plus NAME (50 micrograms/kg/min) starting at T1. The NAME group received only NSR and NAME. Hemodynamic data, regional blood flow, and gastric intramucosal pH (pHi) were measured hourly. LPS increased renal and carotid blood flow consistent with a hyperdynamic state. Mesenteric blood flow was decreased. Treatment of endotoxic animals with NAME decreased renal and carotid blood flow. Mesenteric blood flow and gastric pHi were improved by NAME. NO inhibition in endotoxic shock results in decreased carotid and renal blood flow, by decreasing cardiac output. Mesenteric blood flow and perfusion were improved; however, this requires further study for validation.