Post-Transplant Nerve Regrowth Better with Young Hearts, Quick Surgery

Spontaneous nerve regeneration after a heart transplant is more likely in cases involving young donors, young recipients and fast, uncomplicated surgery, researchers report in today's rapid access issue of Circulation: Journal of the American Heart Association.

Nerve regrowth (reinnervation) to the left ventricle can improve exercise performance, blood flow regulation, and ventricular function. It also allows the sensation of chest pain as an important warning sign of coronary blockage.

Sympathetic nerve fibers are severed during heart transplant surgery. Reinnervation takes time, so it is more frequently observed months or years after surgery. Reinnervation often is partial, but some patients experience no regrowth, explains lead author, Frank M. Bengel, M.D., an assistant professor at Nuklearmedizinische Klink und Polinklinik der Technische Unviersitat in Munchen, Germany.

German scientists explored factors that may influence reinnervation in the largest group of patients assessed for ventricular reinnervation to date. The study also investigated the impact of regrowth on transplant survival.

Seventy-seven heart transplant patients (11 of them women) who were not experiencing organ rejection or other severe problems were examined with positron emission tomography (PET scan). A PET scan provides a cross-sectional image of the heart and heart tissue function.

Follow-up ranged from 1.5 years to 19 years after transplantation. Recipients ranged in age from 23 to 60; donor age ranged from 13 to 59. Duration of surgery (measured by the amount of time the recipients' aorta was clamped) varied from about a half hour to nearly 3 hours.

In 52 patients, researchers found partial reinnervation, while 25 patients had no evidence of nerve regrowth when checked at various times after surgery. Among those with regrowth, nerves were restored in 21 percent of the left ventricular heart muscle.

Reinnervation was greater with more passage of time after surgery, with hearts from younger donors and in younger recipients. Researchers also noted that recipients who underwent shorter surgery had more reinnervation.

Reinnervation did not significantly impact survival.

The molecular mechanisms involved remain unclear. However, researchers note that studies of peripherial nerves show that regeneration of those nerves depend on neural growth factors that may be reduced with increasing age.

"In addition, surgical dissection of the nerves requires nerve fibers to regrow along arteries to reach the new heart," Bengel says. "Extensive scar tissue along this path may impede the regrowth. Hence, extensive reinnervation is more likely if there were few complications during transplant surgery.

"This study suggests that sympathetic reinnervation after heart transplant is not simply a function of time," he says.

While urging that the study be interpreted with caution, researchers conclude that more rapid and intense reinnervation can be expected if hearts of younger donors are chosen and if the procedure is fast and uncomplicated. In addition, transplant recipients who are younger or those with few rejection episodes can expect a higher likelihood of reinnervation and thus higher likelihood for improved exercise capacity and heart function.

Co-authors of the study are Peter Ueberfuhr, M.D.; Thomas Hesse; Nina Schiepel; Sibylle I. Ziegler, Ph.D.; Siegfried Scholz, M.D.; Stephan G. Nekolla, Ph.D., Bruno Reichart, M.D.; and Markus Schwaiger, M.D.