Cardioprotective effects of mitochondrial KATP channels activated at different time

Recent studies in adult hearts have indicated that KATP channels in the inner mitochondrial membrane are responsible for the protection. And we investigated whether opening of mitochondrial KATP channels (mKATP) could provide myocardial protection for immature rabbits and determined its role in cardioprotection.

Thirty-four 3-4-week-old rabbits, weighing 300 - 350 g, were divided randomly into five groups: Group I (control group, n = 8); Group II [diazoxide preconditioning group; n = 8; the hearts were pretreated with 100 micromol/L diazoxide for 5 minutes followed by 10-minute wash out with Krebs-Henseleit buffer (KHB)]; Group III [diazoxide + 5-hydroxydeconate (5-HD) preconditioning group; n = 5; the hearts were pretreated with 100 micromol/L diazoxide and 100 micromol/L 5-HD); Group IV (diazoxide + cardioplegia group; n = 8; cardioplegia containing 100 micromol/L diazoxide perfused the hearts for 5 minutes before ischemia); Group V (diazoxide + 5-HD + cardioplegia group; n = 5; the cardioplegia contained 100 micromol/L diazoxide and 100 micro mol/L 5-HD). All hearts were excised and connected to langendrff perfusion system and passively perfused with KHB at 38 degrees C under a pressure of 70 cmH(2)O. After reperfusion, the recovery rate of left ventricular diastolic pressure (LVDP), +/-dp/dtmax, coronary flow (CF), the creatinine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) in coronary sinus venous effluent and the tissue ATP were measured. Mitochondria were evaluated semiquantitatively by morphology.

After ischemia and reperfusion (I/R), the two groups that were treated by diazoxide only (Groups II and IV) had a significant improvement in LVDP, +/-dp/dtmax, and CF recovery. AST, LDH, and CK were decreased, and the levels of tissue ATP in the two groups were higher. Mitochondria was protected better in Group IV than in other groups.

Activating mKATP channels before and during ischemia can similarly protect immature rabbit hearts, and the mechanism is related to the direct protective effect on mitochondria. Opening of mKATP channel during ischemia provides a better protection for mitochondria than it does before ischemia.