The mitochondrial calcium-activated potassium channel (mitoK(Ca)) and the mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) are both involved in cardiac preconditioning. Here, we examined whether these two channels are also involved in ischemic or pharmacological postconditioning. Using Langendorff perfusion, rat hearts were made hypoxic for 45 min and then reoxygenated for 30 min. Ischemic postconditioning (IPT) was achieved through application of 3 cycles of 10 s of reperfusion and 10 s of ischemia before reoxygenation, with and without paxilline (Pax; a mitoK(Ca) blocker) or 5-hydroxydecanoate (5-HD; a mitoK(ATP) blocker). Pharmacological postconditioning was carried out for 5 min at the onset of reoxygenation using NS1619 (a mitoK(Ca) opener) or diazoxide (Dia; a mitoK(ATP) opener). Pax and 5-HD abolished IPT-induced cardioprotection from reoxygenation injury, whereas administration of NS1619 or Dia significantly improved cardiac contractile activity and reduced aspartate aminotransferase (an index of myocyte injury) release following reoxygenation. In addition, isolated rat myocytes were loaded with tetramethylrhodamine methyl ester (TMRE; fluorescent mitochondrial membrane potential indicator) and 2',7'-dichlorofluorescein [DCFH; fluorescent reactive oxygen species (ROS) indicator] or Fluo-4-acetoxymethyl ester (Fluo-4-AM; fluorescent calcium indicator). When TMRE-loaded myocytes were laser illuminated, the DCFH and Fluo-4 fluorescence increased, and TMRE fluorescence decreased. These effects were significantly inhibited by NS1619 and Dia. We therefore conclude that IPT may protect the heart through activation of mitoK(ATP) and mitoK(Ca) channels, and that opening of these channels at the onset of reoxygenation protects the heart from reoxygenation injury, most likely by reducing excess generation of ROS and the resultant Ca(2+) overload.

It is unclear whether nitrous oxide (N(2)O) has a protective effect on cardiac function in vitro. In addition, little is known about the cardioprotective effect of anesthesia administered during hypoxia or ischemia. We therefore studied the cardioprotective effects of N(2)O and sevoflurane administered before or during hypoxia in isolated rat hearts. Rat hearts were excised and perfused using the Langendorff technique. For hypoxia-reoxygenation, hearts were made hypoxic (95% N(2), 5% CO(2)) for 45 min and then reoxygenated (95% O(2), 5% CO(2)) for 40 min (control: CT group). Preconditioning was achieved through three cycles of application of 4% sevoflurane (sevo-pre group) or 50% N(2)O (N(2)O-pre group) for 5 min with 5-min washouts in between. Hypoxic conditions were achieved by administering the 4% sevoflurane (sevo-hypo group) or 50% N(2)O (N(2)O-hypo group) during the 45-min hypoxic period. L-type calcium channel currents (I(Ca,L)) were recorded on rabbit myocytes. (1) Both 4% sevoflurane and 50% N(2)O significantly reduced left ventricular developed pressure (LVDP). Sevoflurane also increased left ventricular end-diastolic pressure, though N(2)O did not. (2) The recoveries of LVDP and pressure-rate product (PRP) after hypoxia-reoxygenation were better in the sevo-pre group than in the CT or N(2)O-pre group. (3) Application of either sevoflurane or N(2)O during hypoxia improved recovery of LVDP and PRP, and GOT release was significantly lower than in the CT group. (4) Sevoflurane and N(2)O reduced I(Ca,L) to similar extents. Although sevoflurane administered before or during hypoxia exerts a cardioprotective effect, while N(2)O shows a cardioprotective effect only when administered during hypoxia.

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