Indoramin in heart failure: possible adverse effects on hemodynamics and exercise capacity

Indoramin is an alpha 1-adrenergic antagonist vasodilator of potential value in heart failure. We measured hemodynamics and exercise capacity in 12 patients with heart failure, before and after 1 week of indoramin dosing, 75 mg b.i.d. Maximal hemodynamic effects 2 hours after the first dose of indoramin consisted of reduced mean systemic arterial pressure from 96.0 +/- 15.3 to 87.9 +/- 15.3 mm Hg (P less than 0.05) and pulmonary wedge pressure from 23.6 +/- 7.8 to 16.9 +/- 6.6 mm Hg (P less than 0.001). Heart rate, cardiac index, and total systemic resistance did not change acutely after indoramin, but after 1 week mean systemic arterial pressure was still reduced whereas cardiac index fell from 2.69 +/- 0.38 to 2.32 +/- 0.44 L/min/m2 (P less than 0.05) and total systemic resistance rose from 20.4 +/- 2.8 to 21.9 +/- 4.0 U (P less than 0.1). After 1 week maximal exercise oxygen uptake fell from 16.8 +/- 5.6 to 12.5 +/- 3.5 ml/min/kg (P less than 0.02). This limited observation suggests that indoramin is a predominant venodilator acutely in patients with heart failure but that despite this effect it may worsen functional capacity and hemodynamics during continuous dosing in these patients.