| Abstrakt: |
The direct cardiac effects of hydralazine were studied in isolated working rat heart, isolated cat right ventricular papillary muscle, and isolated rabbit right atrium. The haemodynamics, myocardial energetics, and contractility of isolated hearts were measured at hydralazine concentrations of 0.01, 0.1, 0.5, 1.0, 10 and 100 μmol·litre−1. Coronary flow was significantly increased (≥21%, p<0.01) in paced (325 beats·min−1) rat hearts at ≥0.5 μmol·litre−1 hydralazine and in spontaneously beating hearts (≥37%; p<0.05) at ≥1.0 μmol·litre−1 hydralazine. The increases in coronary flow occurred without significant increases in heart rate, contractility (dP/dtmax), or coronary perfusion pressure. Myocardial oxygen consumption was not significantly changed at any hydralazine concentration in spontaneously beating hearts and was unaltered in paced hearts except for a small significant increase (9.8%) at 10 μmol·litre−1. A negative inotropic effect was apparent at 100 μmol·litre−1 hydralazine as indicated by a significant reduction of dP/dtmax (paced and non-paced hearts), peak aortic flow rate (non-paced), and maximum left ventricular pressure (paced). In isolated cat papillary muscles and rabbit right atria, cumulative hydralazine log dose-response curves (0.1-1000 μmol·litre−1) were obtained. A positive inotropic effect that could be abolished by beta adrenergic blockade was produced in papillary muscles only at concentrations ≥ 100 μmol·litre−1. A dose dependent negative chronotropic effect occurred at hydralazine concentrations ≥10 μmol·litre−1 in isolated rabbit atria. Thus hydralazine mediated increases in coronary flow may occur at therapeutic concentrations in the absence of an increase in coronary perfusion pressure or myocardial oxygen demand. Hydralazine did not induce direct positive inotropic or chronotropic effects at concentrations obtained clinically. At supratherapeutic drug concentrations species specific inotropic and chronotropic effects were apparent. [ABSTRACT FROM PUBLISHER] |
