Dependence of enhanced maximal exercise performance on increased peak skeletal muscle perfusion during long-term captopril therapy in heart failure

Maximal oxygen uptake (VO₂), skeletal muscle blood flow by xenon-133 washout technique and femoral vein arteriovenous oxygen difference and lactate were measured at rest and during maximal bicycle exercise in eight patients with severe congestive heart failure before and after 8 weeks of therapy with Captopril. During therapy, skeletal muscle blood flow at rest increased significantly from 1.5 ± 0.6 to 2.6 ± 1.0 ml/100 g per min (p < 0.05), with a concomitant decrease in the femoral arteriovenous oxygen difference from 10.0 ± 1.7 to 8.3 ± 1.9 ml/100 ml (p < 0.05). Maximal V0₂ increased significantly from 13.4 ± 3.0 to 15.5 ± 4.1 ml/kg per min (p < 0.05). In four patients, the increase in maximal V0₂ averaged 3.7 ml/kg per min (range 2.7 to 4.9), whereas in the remaining four patients, it was < 1 ml/kg per min. Overall, peak skeletal muscle blood flow attained during exercise did not change significantly during long- term therapy with Captopril (19.6 ± 6.2 versus 27.6 ± 14.3 ml/100 g per min, p = NS). However, the four patients with a significant increase in maximal VO₂ experienced substantial increases in peak skeletal muscle blood flow and the latter changes were linearly correlated with changes in maximal VO₂ (r = 0.95, p < 0.001). Femoral arteriovenous oxygen difference at peak exercise was unchanged (12.6 ± 2.6 versus 12.6 ± 2.4 ml/100 ml). Thus, improvement in maximal VO₂ produced by long-term therapy with Captopril is associated with an increased peripheral vasodilatory response to exercise, and this improvement only occurs when the peak blood flow is augmented. Moreover, improvement in exercise performance is not a result of heightened oxygen extraction by the skeletal muscle.