Myocardial innervation in long-term heart transplant survivors: a quantitative ultrastructural survey

There is no physiologic evidence for reinnervation of the transplanted human heart, although some nerves have been observed histologically. Our purpose was to find out if there was any anatomic evidence of an increase in myocardial innervation density with time in long-term heart transplant survivors. We used electron microscopic methods to estimate the number of nerves per unit area in right-sided endomyocardial biopsies from five patients at 1 year after transplantation, five at 5 years, and one each at 9, 10, and 12 years. Five donor hearts with no disease were used as controls. The mean number of nerves (either single axons or bundles of axon profiles) per square millimeter was 216 (standard deviation [SD] 79) in control hearts, 10 (SD 12) in 1 year transplants, four (SD 7) at 5 years, and three (SD 4) at 9 to 12 years. The difference between control and transplanted hearts was significant (p less than 0.001, one-way analysis of variance). There was no significant difference in the mean number of axon profiles per nerve. The few nerves that can be found in the transplanted heart, even at 12 years, might be donor postganglionic parasympathetic neurons, which are never lost. Accordingly, we found rare axon varicosities, containing vesicles, near myocytes at 1, 5, 9, and 12 years. We conclude that normal myocardial innervation is not likely to be restored in transplanted human hearts.