Hemodynamic effects of prazosin in chronic heart failure

Three series of investigations were carried out with prazosin (PZN) hydrochloride. In the first, hemodynamic effects of PZN were compared with those of hydralazine (HDZ) in 11 patients with chronic congestive heart failure (CHF). In doses up to 5 mg, PZN increased cardiac output (CO) 20% accompanied by a 20% decrease in pulmonary capillary wedge pressure (LVFP). HDZ increased CO by 50% with little or no effect on LVFP. An additional 12 patients were given multiple 5 mg doses of PZN at 6-hour intervals with measurements of hemodynamic and plasma blood levels. Results suggested an attenuation of the effects of PZN on increasing CO but not on decreasing LVFP. This attenuation of CO was not due to inadequate plasma levels. Acute exercise studies (supine bicycle) were performed in 10 patients with severe CHF before and after the administration of several doses of PZN. There appeared to be a greater effect of PZN during exercise than at rest, with a beneficial increase in CO and reduction in LVFP. These data suggest that, despite hemodynamic attenuation of its effects on CO at rest, PZN may still be beneficial to active patients with CHF. In vitro studies with various vasodilators were performed to evaluate potential intropic effects. Isometric force (cat papillary muscle) increased 2% with 10-4M and 31% with 10-3M HDZ. PZN increased force 4% at 10-6M and 18% at 10-4M. Captopril did not increase force development at any dose level. The doses of HDZ and PZN that increased force development were higher than usual clinical doses.