Hemodynamic Interactions of Anesthetics and K Channel Openers in Chronically Instrumented Dogs

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The present study was carried out to determine the hemodynamic interactions of KATP channel openers and anesthetics in chronically instrumented dogs.Dogs were chronically instrumented to measure mean arterial pressure (MAP), heart rate (HR), left circumflex coronary blood flow (CBF), cardiac output (CO), and regional contractile function (%SS). Hemodynamics were measured continuously in the conscious state or during anesthesia.The KATP channel openers, cromakalim, nicorandil and JTV-506, were shown to have selectively potent effect on coronary vasodilation. The effects of coronary vasodilation caused by isoflurane and sevoflurane were completely abolished by a KATP channel closer, glibenclamide, suggesting that the activity of KATP channels might contribute the mechanism underlying volatile anesthetics on vasodilation. Isoflurane enhances the vasodilating action of cromakalim on both systemic and coronary vasculature and attenuates the cromakalim-induced increases in CO and myocardial contractility. The results also suggest that when the pharmacology of KATP channel openers are studied in animals, the effect of anesthetics should be excluded. The experiment of arrhythmias indicated that Ito but not KATP channels might be involved in the mechanism in producing halothane-epinephrine arrhythmias.