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Ranolazine as an Adjunct to Cardioplegia: A Potential New Therapeutic Application

Heart Institute, Good Samaritan Hospital, Los Angeles, California

Joseph M. Arcidi, Jr, MD

Section of Cardiac and Thoracic Surgery, Good Samaritan Hospital, Los Angeles, California

Sharon L. Hale, BS

Heart Institute, Good Samaritan Hospital, Los Angeles, California

Boris Z. Simkhovich, MD, PhD

Heart Institute, Good Samaritan Hospital, Los Angeles, California

Luiz Belardinelli, MD

CV Therapeutics Inc, Palo Alto, California

Arvinder K. Dhalla, PhD

Section of Cardiac and Thoracic Surgery Good Samaritan Hospital, Los Angeles, California

John C. Shryock, PhD

Section of Cardiac and Thoracic Surgery Good Samaritan Hospital, Los Angeles, California

Robert A. Kloner, MD, PhD

Heart Institute, Good Samaritan Hospital, Los Angeles, California, rkloner{at}goodsam.org, and Division of Cardiovascular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California

The purpose of this study was to examine the therapeutic potential of ranolazine, a novel antianginal drug, as an adjunctive therapy to hyperkalemic cardioplegia. Rat hearts were Langendorff-perfused and exposed to 40 minutes of ischemia and 30 minutes of reperfusion without (control) or with cardioplegia or cardioplegia with 50 µmol/L ranolazine. During ischemia, cardioplegia prolonged time to contracture, defined as the time to reach an intraventricular pressure of 20 mm Hg, from 12 + 1 minute (control) to 25 + 2 minutes (P < .05). Ranolazine supplement further lengthened the time to contracture to 34 + 2 minutes (P < .05). Ischemia/reperfusion caused a dramatic elevation in left ventricular end diastolic pressure (LVEDP) during reperfusion. Cardioplegia lessened the LVEDP elevation measured at 30 minutes of reperfusion from 76 + 3 mm Hg (control) to 32 + 3 mm Hg (P < .05). The increase in LVEDP was reduced even further to 17 + 2 mm Hg in hearts receiving cardioplegia plus ranolazine (P < .05). These results suggest that addition of ranolazine during hyperkalemic ischemic cardioplegic arrest is beneficial and provides further protection against contracture.

Key Words: ranolazine • cardioplegia • contracture • late Na+ current inhibitor • ischemia/reperfusion

This version was published on June 1, 2009

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 14, No. 2, 125-133 (2009)
DOI: 10.1177/1074248409333491


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				H. Hwang, J. M. Arcidi Jr, S. L. Hale, B. Z. Simkhovich, L. Belardinelli, A. K. Dhalla, J. C. Shryock, and R. A. Kloner Ranolazine as a Cardioplegia Additive Improves Recovery of Diastolic Function in Isolated Rat Hearts Circulation, September 15, 2009; 120(11_suppl_1): S16 - S21. [Abstract] [Full Text] [PDF]