Captopril versus placebo in congestive heart failure: effects on oxygen delivery to exercising skeletal muscle

The effects of captopril versus placebo on oxygen consumption in the exercising leg have been examined using Doppler measurements of femoral flow and arteriovenous oxygen difference. Twenty patients with heart failure were randomized to captopril 25 mg (N = 10) or placebo (N = 10). Maximal supine exercise of one leg was performed before treatment and again 1 h and 4 h afterwards. Systemic haemodynamic variables were unaffected by placebo, but captopril increased stroke index at peak exercise from 26 +/- 3 to 34 +/- 3 ml beat-1 m-2 and reduced pulmonary artery wedge pressure from 26 +/- 3 to 16 +/- 3 mmHg (P less than 0.05). Despite the captopril-induced improvement in left ventricular function, exercise duration did not increase significantly and peak values for femoral flow (1059 +/- 178 to 938 +/- 134 ml min-1, P = NS), and oxygen consumption (134 +/- 26 to 111 +/- 18 ml min-1, P = NS) in the exercising leg were unaffected. Cutaneous flow, as reflected by skin temperature (27.5 +/- 0.4 to 27.6 +/- 0.4 degrees C, P = NS), was also unaffected. In the patients randomized to captopril, the acute improvement in left ventricular function was abbreviated and, after 4 h, all variables had returned towards baseline. Moreover, when the invasive studies were repeated after four weeks chronic treatment responsiveness to converting enzyme inhibition had attenuated and there were no detectable differences between the captopril and placebo groups. These data have demonstrated an acute captopril-induced improvement in left ventricular function in patients with congestive heart failure. Nevertheless the beneficial acute response was abbreviated predicting the development of early tolerance. Oxygen delivery to the exercising leg showed no tendency to increase either acutely when left ventricular function was significantly improved, or chronically when systemic responsiveness had attenuated. Thus irrespective of its effects on left ventricular function, captopril does not increase nutritive flow to exercising skeletal muscle in congestive heart failure.