Effects of isosorbide dinitrate and hydralazine on regional metabolic responses to arm exercise in patients with heart failure

The reduced exercise capacity of patients with heart failure is thought to be due in part to impaired skeletal muscle oxygen delivery. To determine if hydralazine and isosorbide dinitrate improve skeletal muscle oxygen delivery in such patients, the effects of these agents on regional metabolic responses to forearm exercise were examined in 16 patients with heart failure. Arm oxygen extraction and brachial venous lactate concentration were measured at rest and during 3 minutes of rhythmic handgrip and then remeasured after administration of oral hydralazine (nine patients) or sublingual isosorbide dinitrate (nine patients). Hydralazine increased mean (± standard deviation) cardiac output at rest from 3.5 ± 0.5 to 4.9 ±1.0 liters/min (p < 0.01) and decreased arm oxygen extraction from 39 ± 8 to 33 ± 10 percent (probability [p] < 0.01), suggesting improved resting limb oxygen delivery. However, hydralazine did not reduce arm oxygen extraction during exercise (control 63 ± 4, hydralazine 60 ± 12 percent; p = notsignificant[NS]) or venous lactate during exercise (control 16.6 ± 7.8, hydralazine 17.1 ± 4.8 mg/100 ml; p = NS). Isosorbide dinitrate increased the cardiac output from 3.6 ± 0.7 to 4.5 ± 0.7 liters/min (p < 0.01) but had no effect on arm oxygen extraction at rest (control 40 ± 11, isosorbide dinitrate 38 ± 11 percent; p = NS) and during exercise (control 66 ± 5, isosorbide dinitrate 64 ± 8 percent; p = NS) or on venous lactate during exercise (control 17.9 ± 6.4, isosorbide dinitrate 17.1 ± 3.9 mg/100 ml; p = NS). These data suggest that hydralazine and isosorbide dinitrate do not improve skeletal muscle oxygen delivery during exercise in patients with heart failure.