The effects of amrinone versus dobutamine on myocardial mechanics and energetics after hypothermic global ischemia.
The effects on the postischemic myocardium of amrinone and dobutamine were studied in canine hearts that underwent 90 minutes of hypothermic (10 degrees C) arrested ischemia. In an isolated heart preparation cross-circulated by a support dog, left ventricular pressure-volume loops were collected under a constant afterload based on a mock circulatory system and a range of preload conditions controlled by a computerized servo volume pump. Dobutamine (0, 5, 10, 15 micrograms/kg per minute) and amrinone (0, 0.75, 1.5, 3.0 mg/kg) were tested in this order based on the weights of the support dogs in eight experiments. Changes in intrinsic myocardial contractility were analyzed as percent increases in the preload recruitable stroke work area from baselines. Dobutamine exhibited significant dose-related increases in the preload recruitable stroke work area. Amrinone did not produce significant increases in preload recruitable stroke work area at 0.75 mg/kg; amrinone's inotropic effect was equivalent to dobutamine, 5 micrograms/kg per minute at 1.5 mg/kg, and at the maximum dose (3.0 mg/kg) it was equivalent to dobutamine, 10 micrograms/kg per minute. The myocardial energetic efficiency was determined from the analysis of the myocardial oxygen consumption-pressure volume area relationship. The y intercept represents the basal metabolic oxygen requirement of the unloaded beating heart, and the slope is inversely proportional to the rate of energy conversion for increasing loading conditions. Dobutamine significantly increased the y intercepts, but it had no effects on the slopes. These changes demonstrate reduced myocardial efficiencies that are consistent with previous reports. Amrinone (0.75 and 1.50 mg/kg) did not result in change of the y intercepts and the slopes of myocardial oxygen consumption-pressure-volume area relationship from baseline conditions. The y intercept was increased with amrinone (3.0 mg/kg), although still not significantly higher than baseline and not to the extents of the dobutamine group. Dobutamine did not have any primary effect on coronary resistance, while amrinone significantly reduced coronary resistance in all loading conditions at 1.5 and 3.0 mg/kg. This study demonstrates that the inotropic effects of amrinone tested under this constant afterload preparation were lower than those of dobutamine. Amrinone has a superior profile of myocardial efficiency on the postischemic myocardium since it does not produce the oxygen-wasting effects of the traditional inotropic agents such as the beta agonists. This benefit, together with amrinone's coronary dilating effects, critically improves the supply/demand ratio that may be of importance in certain clinical situations.
Cardiothoracic Surgery Research Laboratory, New York Hospital-Cornell University Medical College, NY 10021.
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Ko
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Zelano
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Fahey
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Berman
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Lang
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Isom
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Krieger
D000676:Amrinone / Q000494:pharmacology*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects; D004280:Dobutamine / Q000494:pharmacology*; D004285:Dogs; D007036:Hypothermia, Induced; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D013268:Stimulation, Chemical; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D004280:Dobutamine; D000676:Amrinone