[en] Sepsis and its complications, hypotension, shock, and multiorgan failure continue to represent a significant cause of mortality among hospitalized 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 invasive procedures. Activation of cytokines by endotoxins and subsequent formation of nitric oxide is of central pathogeneic importance in sepsis. In this study we show that polymerized bovine hemoglobin (Biopure 2) restores both cardiovascular and renal functions in an endotoxin-induced shock model in rats. These effects are compared to those of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine, and hydroxyethyl 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 normalize cardiovascular and kidney function in acute septic shock. This new therapeutic approach is readily applicable to controlled clinical trials because polymerized hemoglobin has been tested in humans and is therefore available for such studies.
Disciplines :
Neurology
Author, co-author :
HENEKA, Michael ; Department of Pharmacology, University of Tübingen, Germany
Löschmann, Peter-A.; Department of Pharmacology, University of Tübingen, Tübingen, Germany ; Department of Neurology, Experimental Neuropharmacology, University of Tübingen, Tübingen, Germany ; Department of Neurology, Institute of Pharmacology, University of Tübingen, D-72076 Tübingen, Germany
Osswald, Hartmut; Department of Pharmacology, University of Tübingen, Tübingen, Germany
External co-authors :
yes
Language :
English
Title :
Polymerized hemoglobin restores cardiovascular and kidney function in endotoxin-induced shock in the rat.
Publication date :
01 January 1997
Journal title :
Journal of Clinical Investigation
ISSN :
0021-9738
eISSN :
1558-8238
Publisher :
American Society for Clinical Investigation, United States
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