Hemodynamic effects of continuous infusion of AR‐C 239 in left ventricular failure

AR‐C 239 is a new specific alpha 1 antagonist drug with an action similar to that of prazosin. In dogs it appears to be specific for the alpha 1 adrenoreceptor. AR‐C 239 was tested in 11 patients (49 ± 11 years old) with left heart failure, who had not received any previous treatment. The drug was infused intravenously with a stepwise increase in dose, producing three stable plasma concentration plateaus: 10 ± 2, 51 ± 3, and 138 ± 55 ng/ml. Hemodynamic data were collected at time T0 before drug infusion, and half‐way through each infusion. Blood pressures and cardiac output were recorded using a Millar microtip manometer (left ventricle), a Swan‐Ganz catheter (pulmonary artery), and a femoral catheter, connected to a Syscomoram computer system which calculated the following parameters: work, resistances, tension—time index and contractility indices. Left ventricular ejection fraction and volumes were obtained from cineangiograms performed 30 min before drug infusion and at the end of the third infusion plateau. AR‐C 239 produces a dose‐dependent fall in systemic blood pressure (r=0.539, n=33, p<.001). Maximal beneficial effects are reached with the second infusion dose with a dramatic fall in systemic (peripheral) resistance (−30±21%, p±0.01), accompained by a decrease in pulmonary resistance (−22±24%, p<.05), leading to a drop in the tension‐time index (−22±16%, p<.01), a fall in LV filling pressure (−17±8%, p<.001), and an improvement in cardiac index (+20±18%, p<.02). Apart from a reflex‐related increase in heart rate (14±10%, p<.01), the drug does not affect contractility indices such as extrapolated Vmax. No adverse reactions were noted during the experiment. AR‐C 239 appears to be a powerful vasodilator via selective alpha 1 ‐adrenoreceptor blockade. Its good tolerance together with the large range of available dose concentrations indicate that this drug could be useful in the acute management of left heart failure.