EFFECTS OF CARDIAC TRANSPLANTATION ON ENDOTHELIUM-DEPENDENT DILATION OF THE PERIPHERAL VASCULATURE IN CONGESTIVE-HEART-FAILURE

Patients with congestive heart failure demonstrate attenuated endothelium-dependent vasodilation of the peripheral vasculature, but there are no data regarding the effect of therapies on this abnormality or whether this abnormality is reversible. This study was performed to address the hypothesis that abnormalities in endothelium-dependent vasodilation in heart failure are improved by heart transplantation. Forearm blood flow responses to the intraarterial administration of a dose range of methacholine, an endothelium-dependent vasodilator, and nitroprusside, an endothelium-independent vasodilator, were examined in 2 separate protocols. In protocol 1, forearm blood flow responses to methacholine in 14 heart transplant recipients were 5.02 +/- 3.11, 11.55 +/- 7.20 and 11.61 +/- 10.24 ml/min/100 ml forearm volume. These responses were significantly greater than those in 10 patients with heart failure (2.23 +/- 1.22, 4.60 +/- 3.43 and 6.70 +/- 4.91 ml/min/100 ml forearm volume; p <0.05). In contrast, the responses to nitroprusside were nearly identical in the 2 groups. In protocol 2, six patients were studied before and 4 months (range 1 to 11) after transplantation. Methacholine responses before transplantation were 2.5 +/- 1.3, 5.2 +/-1.5 and 7.3 +/- 1.5 ml/min/100 ml forearm volume and were significantly improved after transplantation to 5.7 +/- 1.2, 12.1 +/- 3.0 and 14.2 +/- 2.2 ml/min/100 ml forearm volume (p <0.05). Peak reactive hyperemia responses increased significantly from 19.0 +/- 3.7 to 44.8 +/- 6.4 ml/min/100 ml forearm volume (p <0.01) after transplantation. These data demonstrate that heart transplantation was associated with a significant improvement in the forearm blood flow responses to methacholine. The effect of heart transplantation was consistent when comparing a group of transplant recipients and patients with heart failure and in a separate group of patients studied both before and after transplantation. The improvement in endothelium-dependent vasodilation may occur in the setting of an improvement in overall responsiveness of the peripheral vasculature. These data demonstrate that abnormal endothelium-dependent responses in heart failure are reversible.