Potential value of oral beta 2-adrenoceptor agonists in congestive heart failure: a haemodynamic and metabolic study

Abstract

This study was designed to investigate and compare the haemodynamic and metabolic responses to pirbuterol and salbutamol in patients with congestive heart failure and coronary artery disease. Attention was directed towards the effects these beta 2-adrenoceptor agonists have on left ventricular systolic function, systemic and coronary haemodynamics and myocardial substrate metabolism. Sixteen patients were randomly allocated to treatment with either pirbuterol 20 mg or salbutamol 6 mg. Since no statistically significant differences between the responses to these drugs were observed, combined data for both agents are presented. Ninety minutes after the drug intervention cardiac index increased from 2.2 +/- 0.1 to 2.9 +/- 0.2 1/min per m2 (P less than 0.001) in association with marked reductions in systemic vascular resistance (from 22 +/- 1 to 15 +/- 1 units, P less than 0.001) and increments in left ventricular dp/dtmax (from 1074 +/- 85 to 1422 +/- 133 mm Hg/sec, P less than 0.05). Modest reductions in left ventricular end-diastolic pressure (from 21 +/- 1 to 15 +/- 1 mm Hg, P less than 0.01) were observed. Heart rate increased from 82 +/- 5 to 91 +/- 4 beats/min (P less than 0.01) but the small fall in mean arterial pressure (from 86 +/- 3 to 78 +/- 3 mm Hg) was not significant. Drug-induced coronary vasodilatation reduced coronary coronary vascular resistance from 0.65 +/- 0.06 to 0.47 +/- 0.04 units (P less than 0.01) and led to a marked increase in coronary sinus blood flow (from 124 +/- 9 to 155 +/- 9 ml/min, P less than 0.05). Arterial levels of free fatty acids increased from 0.78 +/- 0.13 to 1.05 +/- 0.18 mmol/l (P less than 0.05) resulting in the preferential utilization of this substrate as a myocardial energy source. Despite the substantial haemodynamic improvement, however, no significant increase in myocardial oxygen uptake or lactate production was observed. Thus, in patients with coronary artery disease and congestive heart failure pirbuterol and salbutamol improve left ventricular function by a combination of afterload reduction and positive inotropism such that no appreciable deterioration in myocardial energetics occurs.