Effects of the blockade of cardiac sarcolemmal ATP-sensitive potassium channels on arrhythmias and coronary flow in ischemia-reperfusion model in isolated rat hearts.
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 micromol/l HMR1098 and 100 micromol/l 5-HD-treated hearts compared to control (P < 0.05). HMR1098, at 3 micromol/l, but not at 30 micromol/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 micromol/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.
Gok
S
S
Celal Bayar University, School of Medicine, Department of Pharmacology, Manisa, 45030, Turkey. sulegok@yahoo.com
Vural
K
K
Sekuri
C
C
Onur
R
R
Tezcan
A
A
Izanli
A
A
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D001549:Benzamides / Q000494:pharmacology; D003326:Coronary Circulation; D003652:Decanoic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate; D006880:Hydroxy Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D014655:Vascular Resistance; D016277:Ventricular Function, Left
D001549:Benzamides; D003652:Decanoic Acids; D006880:Hydroxy Acids; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; C052853:5-hydroxydecanoic acid; C410297:HMR 1098