Background: Although many studies have documented sympathetic re-innervation in transplanted hearts (allografts) using chemical, imaging, and electrophysiologic methods, little histopathologic proof of this process exists.
Methods and results: We used immunohistochemical techniques with antibodies to S-100 protein, to growth-associated protein 43 (GAP43), and to tyrosine hydroxylase (TH) to detect nerves in the left ventricles in allografts from 29 consecutive recipients. Reasons for transplantation included ischemic heart disease (IHD, n=16), non-ischemic dilated cardiomyopathy (DCM, n=12), and both (n=1). We assessed nerve densities (nerves/mm2) with respect to time after transplantation in the endocardium; in the mid-myocardium; and around intramyocardial blood vessels, scars, foci of rejection, and Quilty lesions. Six normal hearts were used for comparison. As in normal hearts, all 29 allografts had epicardial nerve trunks that extended into the mid-myocardium around blood vessels. Although the total number of nerves (S100-positive) progressively decreased over time, GAP43-positive nerves around the blood vessels increased with time (p <0.005). We also observed abundant TH-positive nerves. The density of S100-positive nerves around blood vessels was greater in those undergoing transplantation for IHD (113 +/- 88) than in those with prior DCM (54 +/- 49, p <0.05). Nerve density in each area varied greatly.
Conclusions: Heterogeneous sympathetic nerve sprouting and re-innervation occurred around blood vessels in the allografts. The magnitude of nerve sprouting increased with time and varied greatly from patient to patient. Patients with IHD had greater nerve sprouting and re-innervation than did those with DCM.