Cardiac noradrenergic function one year following cardiac transplantation

Controversy exists whether or not cardiac nerves regrow into a human transplanted heart. The present study examined cardiac noradrenergic function one year following cardiac transplantation. Eight male cardiac transplant recipients having standard triple immunosuppressive treatment were catheterized diagnostically one year after heart transplantation. They had normalized cardiac hemodynamics and showed no histological rejection in biopsies. A second study group, with intact cardiac innervation, consisted of 19 patients with stable angina pectoris class I to III. Cardiac sympathetic nerve activity was assessed by measurements of cardiac noradrenaline (NA) extraction and spillover, using infusion of tritium-labelled NA (3H-NA). To further characterize cardiac noradrenergic function (synthesis and metabolism) arterial and coronary venous plasma concentrations of the NA precursor, dihydroxyphenylalanine (DOPA), the dopamine metabolite, dihydroxyphenylacetic acid (DOPAC), and the intra-neuronal NA metabolite, dihydroxyphenylglycol (DHPG), were also examined. In transplant recipients, cardiac sympathetic function was also examined before and during supine bicycle exercise and after administration of desipramine to block neuronal uptake. Significant dilution of 3H-NA with endogenous NA from arterial to coronary venous plasma in cardiac transplant patients indicated detectable spillover of NA into plasma from transplanted hearts. However, cardiac spillover of NA in heart transplant patients was only a quarter of that observed in angina patients. Also, transplanted hearts showed no production of DOPA, DOPAC, DHPG or 3H-labelled DHPG, whereas there were positive arterial-venous plasma gradients in all these catechols across the hearts of angina patients. Cardiac fractional extraction of NA was 74% in the angina patients, but only 13% in transplant patients. In transplant patients, cardiac spillover of NA and extraction of 3H-NA were not affected by desipramine or exercise. The present study shows little evidence of any functional activity of cardiac sympathetic nerves in the transplanted heart, as assessed by biochemical indices of release, reuptake, metabolism and synthesis of NA. This argues against cardiac reinnervation of functional importance, at least within the first postoperative year.