Research Information System
PHARMACOLOGICAL REPORTS, vol.70, no.1, pp.156-160, 2018 (SCI-Expanded)
Background: Though prasugrel is one of the important P2Y(12) inhibitors currently in use for antiplatelet therapy, its potential effects on contractility and electrical activity of ventricular myocytes have not yet been investigated. Hence this study was designed to study the impact of prasugrel on contractile function and membrane potential of isolated ventricular myocytes. Methods: Freshly isolated rat ventricular myocytes were used in this study. Myocyte contraction was measured during electrical stimulation of cardiomyocytes and the action potential (AP) recordings were obtained with current clamp mode of the patch-clamp amplifier. Results: AP duration and fractional shortening of ventricular myocytes did not show any change with the administration of 1 mu M of prasugrel. However, remarkable depolarization of resting membrane potential followed by apparent fibrillation episodes was detected in the cardiomyocytes. Similar events were observed in the contractile activity of myocytes during field stimulation. Also, a higher concentration of prasugrel (10 mu M) elicited repeated fibrillations, which disappeared after washout or nitric oxide synthase (NOS) inhibition with L-NAME. In contrast, the same concentration of ticagrelor, another P2Y12 inhibitor did not induce fibrillation events though it decreased the contractility of ventricular myocytes significantly. The perfusion of ventricular myocytes with L-NAME did not alter the negative inotropic effect of ticagrelor. Conclusions: Prasugrel, a widely used antithrombotic agent, may induce depolarization in the membrane potential of myocytes as well as fibrillation via NO mediated pathway. (c) 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.