Impact of isradipine on contractile performance, metabolism, and coronary resistance studied in isolated rat hearts.
In anesthetized dogs, isradipine has been reported to induce peripheral vasodilation and increase cardiac output (CO) and myocardial contractility, whereas myocardial oxygen consumption (MVO2) decreases, suggesting that isradipine may increase overall metabolic efficiency of the ventricle of intact animals. Whether isradipine has any direct myocardial effects that could cause intrinsic increase in metabolic efficiency or whether the observation relates to favorable isradipine-induced changes in hemodynamic loading conditions is not known. Therefore, we determined the direct myocardial effects of isradipine on contractile strength and metabolic efficiency in isolated rat heart. Isolated crystalloid perfused rat hearts were instrumented for measurement of ventricular pressure, volume, and MVO2. Isradipine decreased developed pressure (DP) and MVO2 in a concentration-dependent manner; at 32 nM irradipine, both quantities were approximately 70% of their control values. Isradipine caused a downward shift of the end-systolic pressure-volume relation (ESPVR) and in the relation between ventricular work (indexed by pressure-volume area, PVA) and MVO2, indicating that for any given amount of total mechanical work performed, the rat heart consumed less O2 during administration of isradipine than under control conditions. However, the magnitude of the downward shift of this relation was nearly identical to that observed in a separate group of hearts in which we decreased contractility by decreasing the perfusate calcium concentration. Thus, isradipine does not appear to have a contractility-independent effect on myocardial efficiency.
Burkhoff
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D
Cardiology Division, Johns Hopkins Hospital, Baltimore, Maryland.
Gerstenblith
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G
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D017275:Isradipine / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D014655:Vascular Resistance / Q000187:drug effects
D002118:Calcium; D017275:Isradipine