Role of mitochondrial ATP-sensitive potassium channels in dexmedetomidine-induced attenuation of myocardial ischemia-reperfusion injury in rats

Abstract

Objective To evaluate the role of mitochondrial ATP-sensitive potassium (mito-KATP) channels in dexmedetomidine-induced attenuation of myocardial ischemia-reperfusion (I/R) injury in rats. Methods Forty pathogen-free healthy male Sprague-Dawley rats, aged 8-12 weeks, weighing 200-350 g, were divided into 5 groups (n=8 each) using a random number table: sham operation group (group S), I/R group, dexmedetomidine group (group DEX), a specific mito-KATP channel blocker 5-hydroxydecanoate (5-HD) group (group 5-HD) and dexmedetomidine plus 5-HD group (group DEX+ 5-HD). Myocardial I/R was produced by occlusion of the anterior descending branch of the left coronary artery for 30 min followed by 120 min reperfusion in pentobarbital sodium-anesthetized rats.Dexmedetomidine 5 μg/kg was intraperitoneally injected at 15 min prior to reperfusion in group DEX.5-HD 40 mg/kg was intraperitoneally injected at 30 min prior to reperfusion in group 5-HD.In group DEX+ 5-HD, 5-HD 40 mg/kg and dexmedetomidine 5 μg/kg were intraperitoneally injected at 30 and 15 min prior to reperfusion, respectively.The parameters of cardiac function such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and the maximum rate of increase or decrease in left ventricular pressure (±dp/dtmax) were recorded before ischemia (T0) and at 60 and 120 min of reperfusion (T1, 2). Blood samples were collected from the carotid artery at the end of reperfusion for determination of the concentrations of creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) in serum.The animals were then sacrificed, and hearts were removed for determination of the myocardial infarct size in the left ventricular myocardial tissues. Results Compared with group S, the LVSP and ±dp/dtmax were significantly decreased, and the LVEDP was increased at T1-2, and the concentrations of CK-MB and cTnI in serum and myocardial infarct size were increased in the other groups (P 0.05). Compared with group DEX, the LVSP and ±dp/dtmax were significantly decreased, and the LVEDP was increased at T1-2, and the concentrations of CK-MB and cTnI in serum and myocardial infarct size were increased in DEX+ 5-HD group (P<0.05). Conclusion The mechanism by which dexmedetomidine attenuates myocardial I/R injury is partially related to promotion of mito-KATP channel opening in rats. Key words: KATP channels; Dexmedetomidine; Myocardial reperfusion injury