Persistent beneficial effect of postconditioning against infarct size: role of mitochondrial KATP channels during reperfusion
| Autor: | Rong Jiang, Jakob Vinten-Johansen, Robert A. Guyton, Zhi-Qing Zhao, James G. Reeves, Ning-Ping Wang, Hajime Kin, Amanda J. Zatta, James Mykytenko |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Physiology Myocardial Infarction Ischemia Myocardial Reperfusion Injury Pharmacology Mitochondrial Membrane Transport Proteins chemistry.chemical_compound Dogs KATP Channels Coronary Circulation Physiology (medical) Animals Medicine Potassium Channels Inwardly Rectifying Creatine Kinase Membrane potential Cell Death Mitochondrial Permeability Transition Pore business.industry Myocardium MPTP Hypoxia (medical) medicine.disease Myocardial Contraction Potassium channel Disease Models Animal chemistry Mitochondrial permeability transition pore Anesthesia Ischemic Preconditioning Myocardial Tachycardia Ventricular Ischemic preconditioning Female medicine.symptom Cardiology and Cardiovascular Medicine business Reperfusion injury |
| Zdroj: | Basic Research in Cardiology. 103:472-484 |
| ISSN: | 1435-1803 0300-8428 |
| DOI: | 10.1007/s00395-008-0731-2 |
| Popis: | This study tested the hypothesis that inhibition of myocardial injury and modulation of mitochondrial dysfunction by postconditioning (Postcon) after 24 h of reperfusion is associated with activation of KATP channels. Thirty dogs undergoing 60 min of ischemia and 24 h of reperfusion (R) were randomly divided into four groups: Control: no intervention at R; Postcon: three cycles of 30 s R alternating with 30 s re-occlusion were applied at R; 5-hydroxydecanoate (5-HD): the mitochondrial KATP channel blocker was infused 5 min before Postcon; HMR1098: the sarcolemmal KATP channel blocker was administered 5 min before Postcon. After 24 h of R, infarct size was smaller in Postcon relative to Control (27 ± 4%* Vs. 39 ± 2% of area at risk), consistent with a reduction in CK activity (66 ± 7* Vs. 105 ± 7 IU/g). The infarct-sparing effect of Postcon was blocked by 5-HD (48 ± 5%†), but was not altered by HMR1098 (29 ± 3%*), consistent with the change in CK activity (102 ± 8† in 5-HD and 71 ± 6* IU/g in HMR1098). In H9c2 cells exposed to 8 h hypoxia and 3 h of reoxygenation, Postcon up-regulated expression of mito-KATP channel Kir6.1 protein, maintained mitochondrial membrane potential and inhibited mitochondrial permeability transition pore (mPTP) opening evidenced by preserved fluorescent TMRE and calcein staining. The protective effects were blocked by 5-HD, but not by HMR1098. These data suggest that in a clinically relevant model of ischemia-reperfusion (1) Postcon reduces infarct size and decreases CK activity after prolonged reperfusion; (2) protection by Postcon is achieved by opening mitochondrial KATP channels and inhibiting mPTP opening. *P |
| Databáze: | OpenAIRE |
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