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The efficacy and safety of oral amrinone were examined in 17 patients with moderately severe to severe heart failure that was refractory to standard medical therapy and vasodilators. The short-term and 28 week response to open amrinone therapy was assessed first, followed by a placebo-controlled, double-blind withdrawal study of two 13 week stages in nine patients. Rest and exercise ventricular function were determined before and after 32 hours of amrinone; aerobic capacity was serially assessed. After 2 hours, 1.64 mg/kg amrinone produced a 40% (p less than 0.001) increase in cardiac output and a 32% (p less than 0.02) decrease in pulmonary wedge pressure without altering heart rate or blood pressure. The exercise cardiac index-wedge pressure curve obtained 32 hours after the first oral dose was significantly shifted (p less than 0.05) above control values. A sustained improvement in maximal oxygen uptake was noted during long-term open amrinone therapy. Subsequently, seven of the patients randomized to placebo therapy had a significant deterioration of symptoms or exercise tolerance, or both. After 4 weeks of readministration of amrinone, clinical stability was once again established and exercise tolerance was improved by Weeks 8 to 16. Adverse effects of thrombocytopenia (one patient) and hepatic dysfunction (one patient) attributable to amrinone were observed. It is concluded that amrinone is effective in the long-term treatment of chronic cardiac failure.

SUMMARY Pirbuterol (PB), an oral f3-adrenergic-receptor agonist, has the pharmacologic effects of vasodilation and positive inotropy. The present studies were undertaken to determine the value of PB in the long-term therapy of chronic cardiac failure. A double-blind, randomized, 7-week trial comparing PB (20 mg three times daily) with placebo in 12 patients was followed by 12 weeks of open PB therapy. Dosedependent nervousness and tremulousness limited the unit PB dose to < 20 mg in six patients. In all patients, clinical status, exercise tolerance and maximal oxygen uptake, left ventricular echocardiographic dimension and cardiothoracic ratio were unchanged from control after 7 weeks ofplacebo or PB or after 12-19 weeks of PB. To assess the adequacy of 20 mg of PB, the dose-response relations of cardiocirculatory effects to 10, 15, 20 and 30 mg of PB were compared in seven of the above patients and nine other patients. Cardiac output was significantly elevated and wedge pressure reduced after ali four doses, but these changes were sustained for 6 hours after 20-and 30-mg doses only. Thus, the role of PB in the management of chronic cardiac failure appears limited; judgment of its utility must await the results of additional controlled trials.THE PHYSIOLOGIC BASIS for augmenting the performance of the failing heart is rooted in the principles of cardiac muscle mechanics. Muscle fiber shortening, and thereby cardiac output, are enhanced when myocardial contractile state is raised or the load resisting fiber shortening is reduced. i For example, dobutamine is a /31-adrenergic-receptor agonist that augments myocardial contractile state. ' When given intravenously to patients with severe heart failure refractory to standard medical therapy, dobutamine significantly improves ventricular pump function and has therefore proved useful in the short-term treatment of these patients.>9Pharmacologic vasodilation with nitroprusside to attenuate the heightened systemic vascular resistance that accompanies chronic heart failure also raises the output of the failing heart effectively.>4 A theoretically attractive concept for the long-term pharmacologic management of chronic cardiac failure would therefore embrace the principles of augmenting contractility and vasodilation.Pirbuterol is an oral f3-adrenergic-receptor agonist that has positive inotropic and vasodilator properties in dogs.7 In patients with chronic heart failure, Awan et al.8 and Sharma et al.9 found that pirbuterol significantly increased cardiac output while reducing left ventricular filling pressure, and that these salutary hemodynamic effects compared favorably with those of dobutamine.'0 The long-term efficacy and safety of pirbuterol in the management of chronic cardiac fail-

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