Interaction of isoflurane and cromakalim, a KATP channel opener, on coronary and systemic haemodynamics in chronically instrumented dogs.

BACKGROUND: Although isoflurane has been shown to cause coronary and systemic vasodilation through KATP channel activation, the interaction of KATP channel openers and isoflurane has not been fully investigated. The present study was carried out to determine the haemodynamic actions of cromakalim, a KATP channel opener, under the conscious state and during isoflurane anaesthesia in chronically instrumented dogs. METHODS: Fourteen dogs were chronically instrumented to measure systemic and coronary haemodynamics. Each dog was randomly assigned to receive doses of either cromakalim, 4 and 10 microg x kg(-1) i.v., or isoflurane, 2.1% end-tidal (1.5 MAC), plus cromakalim, 4 and 10 microg x kg(-1) i.v. RESULTS: Cromakalim dose-relatedly decreased mean arterial pressure and systemic vascular resistance and increased coronary blood flow in both conscious and anaesthetized states. With isoflurane, the duration of effects of cromakalim were prolonged. Isoflurane exerted an additive effect on the increase in coronary blood flow induced by a low-dose cromakalim, whereas it did not influence the effect of a high-dose cromakalim. The maximum rate of increase in left ventricular pressure and segment shortening were increased by cromakalim in the conscious state but unchanged during isoflurane anaesthesia. CONCLUSION: The results suggest that the coronary vasodilating effects of isoflurane and cromakalim are basically additive until cromakalim exerts the maximal effect, and that the action of cromakalim on the coronary vasculature is prolonged by isoflurane.

Comparative analysis of systemic and coronary hemodynamics during sevoflurane- and isoflurane-induced hypotension in dogs.

We studied the effects of sevoflurane on myocardial contractility and systemic and coronary hemodynamics, as compared with the effects of isoflurane in dogs under the same cardiac work conditions. Sixteen mongrel dogs were anesthetized with alpha-chloralose. Heart was paced at 100 beats/min after producing a complete atrioventricular (A-V) block. Controlled hypotension to a mean arterial pressure (MAP) of 60 mm Hg was induced and maintained by inhalation of either anesthetic, lasting for 60 min. Measurements were made at baseline, 15 min (T1), and 60 min (T2) after starting hypotension, and 30 min after discontinuing equihypotension (T3). Although left ventricular systolic segment shortening (%SS) decreased approximately 20% in both groups, cardiac output (CO) decreased only in sevoflurane during equihypotension (-27.6% at T2). Sevoflurane decreased the coronary blood flow (CBF; -34.8% at T2) with no significant change of coronary vascular resistance (CVR), whereas isoflurane produced a significant decrease in CVR resulting in no change of CBF despite of decreased coronary perfusion pressure (-37.4% at T2). These systemic and coronary vascular effects were continued even at T3. In conclusion, myocardial depressant effects were comparable between sevoflurane and isoflurane. Both systemic and coronary vasodilatory effects of isoflurane are greater than those of sevoflurane.

Systemic and coronary hemodynamic effects of JTV-506, a novel potassium channel opener, in conscious dogs: comparison with cromakalim and nicorandil.

We compared the coronary and systemic hemodynamic effects of JTV-506, a novel potassium channel opener, with those of cromakalim and nicorandil in chronically instrumented conscious dogs. Experiments were performed in 7 dogs which had undergone the implantation of flow probes on the ascending aorta and left circumflex coronary artery, and of catheters into the descending thoracic aorta and left ventricular cavity, respectively. On different days at least 10 days after the implantation, dogs were randomly assigned to the doses of JTV-506 (2, 5 or 10 microg/kg), cromakalim (10 microg/kg), nicorandil (0.2 mg/kg) or glibenclamide (5 mg/kg) plus JTV-506 (5 microg/kg). Each dose of the three drugs produced dose-related increases in heart rate, coronary blood flow, cardiac output, dP/dt(max) and %SS, and produced decreases in arterial blood pressure, left ventricular systolic pressure, and coronary and systemic vascular resistance. JTV-506 at doses of 2 and 5 microg/kg reduced arterial blood pressure only slightly as compared to its significant coronary vasodilating effect. An increase in myocardial oxygen consumption (as estimated by pressure-work index) was also observed in response to each dose of three drugs. At doses that reduced coronary vascular resistance by 75%, JTV-506 produced a greater increase in coronary blood flow, as compared with cromakalim and nicorandil. JTV-506 has the longest duration of action as compared with cromakalim and nicorandil. Glibenclamide pretreatment completely abolished the effects of JTV-506 on coronary and systemic hemodynamics. These results suggest that JTV-506 is relatively more potent in the coronary bed with minimal systemic influence, and exerts a longer time course of action.