Rottlerin Increases Cardiac Contractile Performance and Coronary Perfusion Through BKCa++ Channel Activation After Cold Cardioplegic Arrest in Isolated Hearts

Article; Proceedings Paper

关键词: CA2+-ACTIVATED K+ CHANNELS;    CLINICAL IMPLICATIONS;    POTASSIUM CHANNELS;    BRIEF ISCHEMIA;    BK-CHANNEL;    KINASE;    PHOSPHORYLATION;    PROTECTION;    CONSEQUENCES;    DYSFUNCTION;   

DOI  :  10.1161/CIRCULATIONAHA.110.012112

来源: SCIE

【 摘 要 】

Background-Cardioplegia and cardiopulmonary bypass (CP/CPB) subjects myocardium to complex injurious stimuli that can result in cardiomyocyte and vascular contractile abnormalities. Rottlerin, originally identified as a delta-protein kinase C inhibitor, has a number of known additional effects that may be beneficial in the setting of CP/CPB. We tested the hypothesis that rottlerin mitigates deleterious effects associated with CP/CPB. Methods and Results-Langendorff-perfused isolated rat hearts were subjected to 2 hours intermittent cold (10 degrees C) CP (St Thomas II) followed by 30 minutes normothermic reperfusion. CP was delivered every 30 minutes for 1 minute. Hearts were treated with rottlerin 1 mu mol/L (CP + R) (n = 7) or without rottlerin (CP) (n = 9), and the BKCa++ channel inhibitor paxilline 100 nmol/L was supplied in the CP. Hearts constantly perfused with KHB served as controls (n = 6). Baseline parameters of cardiac function were similar between groups. CP resulted in reduced cardiac function (left ventricular diastolic pressure, 39 +/- 3.8%; +/- dP/dt, 32 +/- 4.4%, -41 +/- 5.1% decrease compared to baseline). Treatment with rottlerin 1 mu mol/L significantly improved CP-induced cardiac function (left ventricular diastolic pressure, 20 +/- 5.9%; +/- dP/dt, 5.2 +/- 4.5%, -11.6 +/- 4.7% decrease versus baseline; P<0.05 CP + R versus CP). Rottlerin also caused a significant increase in coronary flow postreperfusion (CP, 34 +/- 4.2% decrease from baseline; CP + R, 26 +/- 9.6% increase over baseline; P = 0.01). Independent of vascular effects, CP significantly decreased isolated myocyte contraction, which was restored by rottlerin treatment. The BKCa++ channel inhibitor greatly reduced the majority of beneficial effects associated with rottlerin. Conclusions-Rottlerin significantly improves cardiac performance after CP arrest through improved cardiomyocyte contraction and coronary perfusion. (Circulation. 2011; 124[suppl 1]: S55-S61.)

【 授权许可】

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