Effect of Intracoronary Infusions of Amrinone and Dobutarnine on Segment Shortening, Blood Flow, and Oxygen Consumption in In Situ Canine Hearts

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Abstract
Previous in vivo studies assessing the effects of amrinone on myocardial contractility used intravenous infusions, and thus were complicated by varying cardiac loading conditions. Accordingly, the present study was performed in 15 open-chest, anesthetized (fentanyl and midazolam) dogs using infusions of amrinone and dobutamine directly into the left anterior descending artery (LAD). In the LAD bed, percentage of segment shortening (%SS), an index of local myocardial contractility, was assessed with ultrasonic crystals. Coronary blood flow was measured electromagnetically and used to calculate myocardial oxygen consumption and infused drug concentrations. Amrinone and dobutamine were infused separately into the LAD at rates yielding calculated arterial blood concentrations in the clinical range (100, 150, and 200 μg/min, and 2.5,5.0, and 7.5 μg/min, respectively). A mixture of amrinone and dobutamine was also infused into LAD and changes in %SS compared with the sum of the their individual effects. In six of the dogs, an extracorporeal system was used to maintain constant coronary blood flow during amrinone infusions. Amrinone and dobutamine caused individually increases in %SS that were comparable (range, 20%–45%). Myocardial oxygen consumption increased in parallel with %SS for both amrinone and dobutamine. For amrinone, coronary blood flow increased more than myocardial oxygen consumption, resulting in a modest (at highest dose approximately 10%) decrease in oxygen extraction; whereas for dobutamine, coronary blood flow increased in proportion to myocardial oxygen consumption, resulting in no change in oxygen extraction. Increase in %SS caused by combined amrinone and dobutamine was equal to the sum of their individual effects. Amrinone-induced increase in %SS persisted under constant-flow condition. Conclusions: 1) Amrinone had direct positive inotropic effect that is comparable to that of dobutamine in clinical dose range. 2) Amrinone had a weak direct vasodilator effect in coronary circulation. 3) Augmented myocardial contractility by amrinone was independent of the increase in CBF, i.e., Gregg's phenomenon. 4) Inotropic effects of amrinone and dobutamine were additive. (Anesth Analg 1994;79:1066–74)

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