Sustained Reduction of Cardiac Impedance and Preload in Congestive Heart Failure with the Antihypertensive Vasodilator Prazosin

Abstract

To elucidate the hemodynamic effects of prazosin, an antihypertensive agent, in congestive heart failure, we studied 10 patients with ischemic cardiomyopathy and severe ventricular dysfunction. After an oral dose of 2 to 7 mg, heart rate was unchanged (P greater than 0.05). One hour after prazosin administration, mean arterial pressure declined from 95 to 78 mm Hg (P less than 0.001); left ventricular filling pressure declined from 30 to 18 mm Hg (P less than 0.001), cardiac index increased from 2.1 to 2.9 liters per minutes per square meter (P less than 0.001), and systemic vascular resistance fell from 2074 to 1156 dynes sec cm-5 (P less than 0.001). In both forearms vascular resistance and venous tone were reduced (86 to 48 mm Hg per ml per 100 g per minute, and 59 to 18 mm Hg per ml, respectively [P less than 0.001]). All responses persisted for a least six hours (P less than 0.01). Prazosin benefits severe congestive heart failure by inducing a sustained fall of both cardiac preload and impedance.

Efficacy of ambulatory systemic vasodilator therapy with oral prazosin in chronic refractory heart failure. Concomitant relief of pulmonary congestion and elevation of pump output demonstrated by improvements in symptomatology, exercise tolerance, hemodynamics and echocardiography.

“…Upon completion of the exercise test, right heart catheterization was carried out to quantify hemodynamic variables. In each patient, with the Swan-Ganz catheter in place, [40][41][42][43][44][45][46][47][48][49][50] Ag/kg (2 to 7 mg) prazosin was ingested. Cardiac hemodynamics were then remeasured every 30 minutes for six hours following administration of the agent.…”

Results of long-term vasodilator therapy in patients with refractory congestive heart failure.

“…Although overall mortality for the 19 patients who received long-term therapy was poor (actuarial survival of 56% at 12 months), improvement in functional class was associated with relatively good survival; only one of the late responders had died during a follow-up 6 months, five of the nine had improved symptomatically and four remained clinically unchanged; two of the nine patients died during the follow-up period. In these studies the total number of patients with refractory heart failure in whom vasodilator therapy had been attempted was not stated.…”

Acute regional circulatory and renal hemodynamic effects of converting-enzyme inhibition in patients with congestive heart failure.

“…", 10 The lowering of a markedly elevated pulmonary capillary wedge pressure and elevation of depressed cardiac index are accompanied by reduction of systemic vascular resistance in a fashion very similar to the effects of other vasodilator drugs. '7' 18 We have shown that the magnitude of the acute hemodynamic actions is a function of the basal plasma renin activity.9' 10 Such observations contribute to the bulk of evidence that the renin-angiotensin system plays an important role in maintaining the intense peripheral vasoconstriction often seen in patients with severe heart failure. While it is intriguing to speculate that interference with the generation of the naturally occurring vasoconstrictor substance angiotensin II might be responsible for the effects of converting-enzyme inhibitors, these agents also block degradation of the intrinsic vasodilator bradykinin.19 21 Because the activity of the kallikreinkinin system was not measured, we cannot exclude accumulation of bradykinin as a cause of vasodilatation.…”