Cardioprotection of mitoSlo1 channel activation involves mitochondrial permeability transition in ischemia and reperfusion of rat hearts / 浙江大学学报·医学版

ABSTRACT

<p><b>OBJECTIVE</b>To investigate whether the cardioprotection of mitochondrial Slo channel (mitoSlo(1) channel) is associated with mitochondrial permeability transition in isolated rat hearts subjected to ischemia and reperfusion.</p><p><b>METHODS</b>Isolated perfused rat hearts were subjected to 30 min regional ischemia (occlusion of left anterior descending artery) and 120 min reperfusion. The infarct size, lactate dehydrogenase (LDH) release during reperfusion and ventricular hemodynamic parameters were measured.</p><p><b>RESULTS</b>Pretreatment with mitoSlo(1) channel opener, NS1619 10 micromol/L for 10 min reduced the infarct size and LDH release, and improved the recovery of left ventricular developed pressure, left ventricular end-diastolic pressure, maximal rise/fall rate of left ventricular pressure and coronary flow during reperfusion. Administration of atractyloside (20 micromol/L), an opener of mitochondrial permeability transition pore, for 20 min (last 5 min of ischemia and first 15 min of reperfusion) attenuated the reduction of infarct size and LDH release and improvement of left ventricular performance induced by NS1619. In the isolated mitochondria, a significant inhibition of Ca(2+)-induced swelling was observed when mitochondria were incubated with NS1619.</p><p><b>CONCLUSION</b>MitoSlo(1) channel activation by NS1619 protects the myocardium against ischemia and reperfusion injury by inhibiting mitochondrial permeability transition pore opening.</p>