Effect of endogenous and inhaled nitric oxide on the ventilation-perfusion relationships in oleic-acid lung injury.
Previous investigations have shown that the ventilation-perfusion (VA/Q) mismatch caused by acute lung injury can be alleviated either by inducing vasodilation in ventilated lung units with inhaled nitric oxide (NO) or by inhibiting the synthesis of endogenous NO, which opposes hypoxic pulmonary vasoconstriction. To determine the effects of a combination of these interventions, we evaluated cardiopulmonary function and VA/Q distributions in 10 dogs with oleic acid-induced lung injury. Each animal received, in random order, zero or 40 ppm of NO in inspiratory gas, with and without intravenous infusion of NG-monomethyl-L-arginine (L-NMMA) (5 mg/kg/h). The multiple inert-gas elimination technique was used to estimate VA/Q distributions. Systemic L-NMMA administration alone did not affect VA/Q inequality and gas exchange, but increased pulmonary and systemic vascular resistance. Inhaled NO improved gas exchange by redistributing blood flow from shunt units to lung units with a nearly ideal VA/Q ratio, without affecting pulmonary or systemic vascular resistance. Improved VA/Q matching and gas exchange was most pronounced when NO was inhaled in the presence of systemic L-NMMA. Inhalation of NO reversed the pulmonary but not the systemic vasoconstriction caused by L-NMMA. These results suggest that endogenous NO release is not limited to hypoxic lung regions in animals with oleic acid-induced lung injury. Inhaled NO reversed L-NMMA-induced pulmonary vasoconstriction and improved VA/Q matching by selectively dilating the pulmonary vasculature in ventilated lung units.
Putensen
C
C
Department of Anesthesiology, College of Medicine, University of South Florida, Tampa 33612-4799.
Räsänen
J
J
Downs
J B
JB
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D005260:Female; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D019301:Oleic Acid; D009829:Oleic Acids; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000503:physiopathology*; D014692:Ventilation-Perfusion Ratio / Q000187:drug effects; D019323:omega-N-Methylarginine
D009829:Oleic Acids; D019323:omega-N-Methylarginine; D019301:Oleic Acid; D009569:Nitric Oxide; D001120:Arginine