POLYMERIZED HEMOGLOBIN RESTORES CARDIOVASCULAR AND KIDNEY-FUNCTION INENDOTOXIN-INDUCED SHOCK IN THE RAT

Sepsis and its complications, hypotension, shock, and multiorgan failu re continue to represent a significant cause of mortality among hospit alized patients, affecting approximately 200,000 patients per year in the US and 100,000 in Europe (Dal Nogare, A.R. 1991. Am. J. Med. Sci. 302:50-65.). Incidence rates appear to be increasing, probably due to an increase in the population with risk factors such as diabetes or in vasive procedures. Activation of cytokines by endotoxins and subsequen t formation of nitric oxide is of central pathogeneic importance in se psis. In this study we show that polymerized bovine hemoglobin (Biopur e 2) restores both cardiovascular and renal functions in an endotoxin- induced shock model in rats. These effects are compared to those of th e nitric oxide synthase inhibitor N-G-nitro-L-arginine, and hydroxyeth yl starch, the latter currently in clinical use for intravenous volume replacement. Our results clearly indicate that polymerized hemoglobin but not nitric oxide synthase inhibition or volume replacement normal ize cardiovascular and kidney function in acute septic shock. This ne cv therapeutic approach is readily applicable to controlled clinical t rials because polymerized hemoglobin has been tested in humans and is therefore available for such studies.