Abstract
It previously has been reported in ischemic rat hearts that local release of noradrenaline triggers ventricular fibrillation via α1A-adrenoceptor stimulation. In order to elucidate the intracellular pathway mediating ventricular fibrillation in this setting, we used inhibitors or activators of protein kinase C in the absence or presence of the α1A-adrnoceptor antagonist WB 4101. Regional ischemia was induced in isolated perfused rat heart by ligature of the left coronary artery. Pharmacological interventions were tested by addition of drugs to the perfusate 10 min prior to ligature and throughout 30 min of ischemia while the epicardial electrocardiogram was continuously monitored. Blockade of protein kinase C by polymyxin B (1 μmol/l) significantly reduced ventricular fibrillation to 40% (from 87% in controls). Similar effects were seen with the protein kinase C inhibitors staurosporine 10 nmol/l (46% vs. 91%) and cremophor RH 40 100 μmol/l (33% vs. 77%). Activation of protein kinase C by 1,2-dioctanoyl-sn-glycerol (DOG, 10 μmol/l) or phorbol 12-myristate 13-acetate (PMA, 10 nmol/l) did not affect ventricular fibrillation. In the presence of the α1A-adrenoceptor antagonist WB 4101 (0.1 μmol/l), which per se suppressed ventricular fibrillation to 17%, both DOG and PMA increased the occurrence of ventricular fibrillation to 73% and 75%, respectively, whereas the inactivate phorbol ester 4alphaphorbol 12,13-didecanoate (4α-PDD, 10 nmol/l) revealed no proarrhythmic effect. In summary, during regional ischemia in the isolated perfused rat heart, α1A-adrenoceptor stimulation induces ventricular fibrillation mainly by activating protein kinase C.
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Received: 4 April 2000, Returned for revision: 9 May 2000, Revision received: 3 August 2000, Accepted: 7 August 2000
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Tölg, R., Schreieck, J., Kurz, T. et al. Ischemia-induced ventricular fibrillation in isolated perfused rat heart: role of alpha1A-adrenoceptor mediated activation of protein kinase C. Basic Res Cardiol 96, 68–74 (2001). https://doi.org/10.1007/s003950170079
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DOI: https://doi.org/10.1007/s003950170079