Reversal of hyperdynamic response to continuous endotoxin administration by inhibition of NO synthesis.
Septic shock is characterized by an increase in cardiac output and a fall in systemic vascular resistance index and mean arterial pressure. Endotoxin alters the smooth muscle function of blood vessels, probably by means of an increased production of the potent vasodilator nitric oxide (NO). The present study was accomplished to determine how the inhibition of NO synthesis influences cardiovascular performance in an ovine model of hyperdynamic endotoxemia. Endotoxemia was induced in five range ewes (41 +/- 2 kg) by continuous infusion of Escherichia coli endotoxin (LPS, 10 ng.kg-1.min-1) over the entire study period. After 24 h of LPS infusion, cardiac output increased from 5.2 +/- 0.3 to 7.9 +/- 0.6 (SE) 1/min (P less than 0.05) and mean arterial pressure and systemic vascular resistance index fell from 92 +/- 5 to 79 +/- 6 mmHg (P = 0.08) and from 1,473 +/- 173 to 824 +/- 108 dyn.s.cm-5.m2 (P less than 0.05), respectively. The pulmonary shunt fraction increased from 0.23 +/- 0.03 to 0.32 +/- 0.03 (P less than 0.05). The intravenous administration of the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (25 mg/kg) 24 h after the start of the LPS infusion changed these values to approximately baseline levels over the subsequent 4 h. Although N omega-nitro-L-arginine methyl ester increased pulmonary arterial pressure and pulmonary vascular resistance (P less than 0.05), right and left ventricular stroke volume index showed no significant changes. It is concluded that NO has a major function in cardiovascular performance in endotoxemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Meyer
J
J
Department of Anesthesiology, University of Texas Medical Branch, Galveston 77550.
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004926:Escherichia coli; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D010101:Oxygen Consumption / Q000187:drug effects; D012756:Sheep
D004731:Endotoxins; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester