Browsing by Author "Izanli, A"

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    The role of ATP sensitive K+ channels and of nitric oxide synthase on myocardial ischemia/reperfusion-induced apoptosis
    Gok, S; Vatansever, S; Vural, K; Sekuri, C; Izanli, A; Tezcan, A; Cilaker, S
    During ischemia, ATP-sensitive K+ channels (KATP channels) open, and this triggers necrotic processes and apoptosis. In this study, we investigated whether selective sarcoplasmic and mitochondrial KATP channel blockers affected myocardial apoptosis and nitric oxide synthase (NOS) activity in a rat model of myocardial ischemia/reperfusion in vitro. Isolated rat hearts were subjected to 30 min of coronary artery occlusion followed by 30 min of reperfusion. A selective sarcKATP channel blocker, HMR1098 and a selective mitoKATP channel blocker, 5-hydroxydecanoate, were added to the perfusion fluid 10 min before occlusion. Myocardial apoptosis was detected immunohistochemically using the TUNEL method. Myocardial inducible NOS (iNOS) and endothelial NOS (eNOS) were determined immunohistochemically. In control hearts, apoptosis induction was associated with a greater immunoreactivity of iNOS than eNOS. Treatment with HMR1098, at a concentration of 3 mu mol/l, significantly reduced the TUNEL-positive cardiomyocytes and this was associated with decreased iNOS and increased eNOS immunoreactivity. When this drug was administered at a higher concentration, at 30 mu mol/l, a more marked reduction in apoptosis was observed but, in contrast to the effects observed at the lower drug concentration, eNOS immunoreactivity was almost completely abolished while iNOS was strong. Moreover, ischemia-induced cardiac dysfunction (e.g. contractile force and recovery of coronary flow) was increased by the higher concentration of HMR 1098. In hearts treated with 5-hydroxydecanoate, myocyte apoptosis was slightly reduced, and this was associated with an almost equal increase in both iNOS and eNOS immunoreactivity. These findings suggest that iNOS appears to be more important than eNOS in the reduction of apoptosis. However, the further inhibition of apoptosis by the higher concentration of HMR 1098 was associated with poorer cardiac function. (C) 2006 Elsevier GmbH. All rights reserved.
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    Effects of the blockade of cardiac sarcolemmal ATP-sensitive potassium channels on arrhythmias and coronary flow in ischemia-reperfusion model in isolated rat hearts
    Gok, S; Vural, K; Sekuri, C; Onur, R; Tezcan, A; Izanli, A
    Activation of ATP-sensitive K+ channels (K-ATP) during ischemia leads to arrhythmias and blockade of these channels exert antiarrhythmic action. In this study, we investigated the effects of HMR1098, a sarcolemmal K-ATP channel blocker and 5-hydroxydeconoate (5-HD), a mitochondrial K-ATP channel blocker on cardiac function and arrhythmias in isolated rat hearts. The hearts were subjected to 30 min coronary occlusion, followed by 30 min reperfusion. In the preischemic period, both HMR 1098 and 5-HD slightly increased coronary perfusion pressure. Coronary occlusion increased the perfusion pressure and decreased the left ventricular developed pressure (LVDP) in both control and drug-treated hearts. However, inhibition of LVDP was greater and recovery of the perfusion pressure was lower in 30 mu mol/l HMR1098 and 100 mu mol/l 5-HD-treated hearts compared to control (P < 0.05). HMR1098, at 3 mu mol/l, but not at 30 mu mol/l, significantly reduced the ratio of bigeminis, couplets and salvos (P < 0.05). Ventricular tachycardia and ventricular fibrillation were not prevented by HMR1098,. at both concentrations, and with 5-HD (100 mu mol/l). These results suggest that blockade of sarcK(ATP) and mitoK(ATP) channels exert weak antiarrhythmic action, but reduce the recovery of coronary perfusion and contractile force, implying that both types of K-ATP channels have beneficial role in the recovery of ischemic rat myocardium. (c) 2005 Elsevier Inc. All rights reserved.