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Comparison of the Electromechanical Effects of Vesnarinone and Amrinone in Isolated Dog Purkinje Strands and Ventricular Trabeculae

Institute of Molecular Pharmacology and Biophysics. University of Cincinnati College of Medicine, Cincinnati, Ohio, Department of Medicinal Physiology. University of Tromso, Tromso, Norway. Department of Physiology, University Medical School of Debrecen, Debrecen, Hungary, and Department of Pharmacology, Albert Szent-György School of Medicine, Szeged, Hungary.

Péter P. Náinási, MD, PhD

Institute of Molecular Pharmacology and Biophysics. University of Cincinnati College of Medicine, Cincinnati, Ohio, Department of Medicinal Physiology. University of Tromso, Tromso, Norway. Department of Physiology, University Medical School of Debrecen, Debrecen, Hungary, and Department of Pharmacology, Albert Szent-György School of Medicine, Szeged, Hungary.

András Varró, MD, PhD

Institute of Molecular Pharmacology and Biophysics. University of Cincinnati College of Medicine, Cincinnati, Ohio, Department of Medicinal Physiology. University of Tromso, Tromso, Norway. Department of Physiology, University Medical School of Debrecen, Debrecen, Hungary, and Department of Pharmacology, Albert Szent-György School of Medicine, Szeged, Hungary.

Arnold Schwartz, PhD

Institute of Molecular Pharmacology and Biophysics. University of Cincinnati College of Medicine, Cincinnati, Ohio, Department of Medicinal Physiology. University of Tromso, Tromso, Norway. Department of Physiology, University Medical School of Debrecen, Debrecen, Hungary, and Department of Pharmacology, Albert Szent-György School of Medicine, Szeged, Hungary.

Background: Conventional microelectrode techniques were used to compare the concentration-dependent effects of vesnarinone (0.1-100 µM) and amrinone (1 µM-1 mm) on action potential duration (APD) and developed force in both isolated dog ventricular trabeculae and Purkinje strands.

Methods and Results: Both drugs increased contractility of trabecular muscle preparations, while, in Purkinje strands, vesnarinone failed to increase developed force during continuous pacing at 2 Hz. Vesnarinone lengthened APD in both preparations; although this effect was more marked in Purkinje strands. Ventricular muscle APD was not affected by amrinone (1 µM to 1 mM), while, in Purkinje strands, amrinone produced a biphasic effect on APD. Low concentrations (1-100 µM) of amrinone shortened Purkinje fiber APD, while only the highest concentration (1 mM) used lengthened APD. In addition, in Purkinje strand preparations the effects of vesnarinone (10 µM) on APD and developed force were proportional to pacing cycle length at frequencies slower than 2 Hz; however, at frequencies faster than 2 Hz vesnarinone decreased developed force while APD was lengthened. In ventricular trabecular muscle preparations, the effects of vesnarinone were not affected by frequency.

Conclusions: These results indicate clear differences between the effects of vesnarinone and amrinone in isolated cardiac preparations. These differences in experimental effects in isolated cardiac preparations may help provide an explanation for the disappointing clinical response of patients in heart failure to amrinone, while vesnarinone has appeared to be beneficial.

Key Words: positive inotropy • phosphodiesterase inhibitors • action potential duration • force development • vesnarinone • amrinone.

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 1, No. 2, 133-140 (1996)
DOI: 10.1177/107424849600100207


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