PLASMA ENDOTHELIN CONCENTRATIONS IN HUMANS WITH END-STAGE HEART-FAILURE AND AFTER HEART-TRANSPLANTATION

Objectives and Background. Endothelin is an endothelium-derived vasoconstrictor peptide that increases systemic and renal vascular resistance at pathophysiologic concentrations. Recent studies have demonstrated its presence in the circulation and its elevation in animals with congestive heart failure, suggesting that endothelin may contribute to the vasoconstrictive state of heart failure. The current study was designed with two objectives: 1) to demonstrate the elevation of circulating endothelin in patients with heart failure, and 2) to determine the short- and long-term response of endothelin levels after heart transplantation. Methods. Plasma endothelin concentrations were measured in two patient groups. Group 1 included 24 patients with end-stage heart failure who were studied during evaluation for potential heart transplantation. Group 2 included 12 patients from Group 1 who had had heart transplantation. Plasma endothelin concentrations were measured before and on days 1, 3 and 7 after heart transplantation. Eight of these patients also had levels measured 3 to 12 months later. Results. Plasma endothelin concentrations were significantly elevated in patients with heart failure compared with those in an age-matched control group (11.7 +/- 1.1 vs. 6.8 +/- 0.3 pg/ml). In response to heart transplantation, plasma endothelin concentrations increased further and were sustained during a long-term follow-up. These later changes were associated with a significant increase in arterial pressure and serum creatinine. Conclusions. This study demonstrates that endothelin concentrations are increased in patients with heart failure and increase further after heart transplantation. It suggests a possible role for endothelin in the cardiovascular and renal adaptive responses to human heart transplantation.