Effects of isoflurane anesthesia on pulmonary vascular response to K+ ATP channel activation and circulatory hypotension in chronically instrumented dogs.

Abstract

The objective of this study was to evaluate the effects of isoflurane anesthesia on the pulmonary vascular responses to exogenous adenosine triphosphate-sensitive potassium (K+ ATP) channel activation and circulatory hypotension compared with responses measured in the conscious state. In addition, the extent to which K+ ATP channel inhibition modulates the pulmonary vascular response to circulatory hypotension in conscious and isoflurane-anesthetized dogs was assessed. Fifteen conditioned, male mongrel dogs were fitted with instruments for long-term monitoring to measure the left pulmonary vascular pressure-flow relation. The dose-response relation to the K+ ATP channel agonist, lemakalim, and the pulmonary vascular response to circulatory hypotension were assessed in conscious and isoflurane-anesthetized (approximately 1.2 minimum alveolar concentration) dogs. The effect of the selective K+ ATP channel antagonist, glibenclamide, on the pulmonary vascular response to hypotension was also assessed in conscious and isoflurane-anesthetized dogs. Isoflurane had no effect on the baseline pulmonary circulation, but it attenuated (P<0.05) the pulmonary vasodilator response to lemakalim. Reducing the mean systemic arterial pressure to approximately 50 mm Hg resulted in pulmonary vasoconstriction (P<0.05) in the conscious state, and this response was attenuated (P<0.05) during isoflurane. Glibenclamide had no effect on the baseline pulmonary circulation, but it potentiated (P<0.05) the pulmonary vasoconstrictor response to hypotension in conscious and isoflurane-anesthetized dogs. These results indicate that K+ ATP-mediated pulmonary vasodilation and the pulmonary vasoconstrictor response to hypotension are attenuated during isoflurane anesthesia. Endogenous K+ ATP channel activation modulates the pulmonary vasoconstrictor response to hypotension in the conscious state, and this effect is preserved during isoflurane anesthesia.