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- Title
Protective Effects of Ranolazine on Ventricular Fibrillation Induced by Activation of the ATP-Dependent Potassium Channel in the Rabbit Heart.
- Authors
Gralinski, Michael R.; Chi, Liguo; Park, James L.; Friedrichs, Gregory S.; Tanhehco, Elaine J.; McCormack, James G.; Lucchesi, Benedict R.; Gralinski, MR; Chi, L; Park, JL; Friedrichs, GS; Tanhehco, EJ; McCormack, JG; Lucchesi, BR
- Abstract
BACKGROUND: The authors studied the antifibrillatory effects of the adenosine-triphosphate (ATP)-sparing metabolic modulator ranolazine in a rabbit isolated heart model in which ventricular fibrillation occurs under conditions of hypoxia/reoxygenation in the presence of the ATP-dependent potassium channel opener pinacidil. METHODS AND RESULTS: Ten minutes after ranolazine or vehicle administration, addition of pinacidil (1.25 µM) to the buffer was followed by a 12-minute hypoxic period and 40 minutes of reoxygenation. At a reduced concentration of ranolazine (10 µM), ventricular fibrillation occurred in 60% of the hearts, compared to 89% in the control group (P = NS). In contrast, only three of nine hearts (33%) treated with 20 µM ranolazine developed ventricular fibrillation (P <.05 vs vehicle). Hemodynamic parameters including coronary perfusion pressure, left ventricular developed pressure, and +/-dP/dt were not affected by the presence of ranolazine in the perfusion medium. Ranolazine did not prevent or modify the negative inotropic or coronary vasodilator actions of pinacidil, suggesting a mechanism of action independent of potassium channel antagonism. CONCLUSIONS: Ranolazine significantly reduced the incidence of ventricular fibrillation in the hypoxic/reoxygenated heart exposed to the ATP-dependent potassium channel opener, pinacidil. The reported ability of ranolazine to prevent the decrease in cellular ATP during periods of a reduced oxygen supply may account for its observed antifibrillatory action. By maintaining intracellular ATP, ranolazine may modulate or prevent further opening of the ATP-dependent potassium channel in response to hypoxia and/or pinacidil.
- Publication
Journal of Cardiovascular Pharmacology & Therapeutics, 1996, Vol 1, Issue 2, p141
- ISSN
1074-2484
- Publication type
journal article
- DOI
10.1177/107424849600100208