Abstract 18539: Intracoronary Ranolazine Bolus Exerts a Transient Coronary Vasodilatory Action in Intact Porcine
Introduction: Ranolazine is a novel antianginal agent that inhibits the late sodium (late INa) current and reduces intracellular calcium overload, thereby improving diastolic compliance and reducing myocardial ischemia. The possibility that intracoronary administration of this agent may cause coronary vasodilation through a direct effect on coronary vasculature has not been explored.
Methods: The effects of intracoronary ranolazine on coronary and systemic hemodynamics were studied in 8 chloralose-anesthetized pigs. A thoracotomy was performed and a transonic flow probe was positioned around the origin of the left anterior descending (LAD) coronary artery. EKGs were obtained via a right ventricular intracavitary lead. Arterial pressure was continuously monitored. Either saline (control), ranolazine, or nitroglycerin was injected into the LAD (2 mL bolus in 10 seconds).
Results: Intracoronary administration of ranolazine at 1/50 of the systemic bolus of 2.4 mg/kg resulted in a significant increase in coronary blood flow (+71% from the baseline) and reduction in coronary vascular resistance (−36%, Fig.). Neither heart rate (baseline 112±4 bpm vs. peak effect 112±5 bpm, p=0.79), mean arterial pressure (baseline 61±6 mmHg vs. peak effect 59±5 mmHg, p=0.22) nor metabolic demand as assessed by rate-pressure product (Fig.) was altered by intracoronary ranolazine. As compared to intracoronary nitroglycerin 100 μg (+83% in the LAD flow), the effect of ranolazine on coronary hemodynamics was comparable in peak value but nearly twice as long in duration. Saline produced no significant changes.
Conclusions: Intracoronary ranolazine bolus exerts a transient dilatory effect that is comparable to nitroglycerin but is more persistent and could be useful in intervention-induced spasm. The precise mechanisms whereby relatively high local concentrations of intracoronary ranolazine act to reduce coronary vascular resistance directly remains to be elucidated.
- © 2010 by American Heart Association, Inc.