Point:Counterpoint Comments The following letters are in response to the Point:Counterpoint: Cardiac denervation does/does not play a major role in exercise limitation after heart transplantation. To the Editor: Denervation affects greatly cardiac function

To the Editor: Denervation affects greatly cardiac function in HTx recipients. However, it is not the main determinant of their reduced aerobic performance (1, 6). Indeed, the latter depends on complex interactions among cardiac, pulmonary, neurohormonal, vascular, and skeletal muscle function (or “dysfunction”). The relative role of each of these factors may vary depending on donor’s heart characteristics, recipient clinical history, and time after HTx (4). In typical adult HTx recipients, increasing cardiac output (e.g., by priming exercise) does not enhance the kinetics of the metabolic phase of the V̇O2 on response to constant-load exercise (3). In addition, near peak muscle blood flow and its time constant at the onset of exercise are within normal values (2). A convincing evidence of the role of peripheral factors in limiting exercise performance after HTx derives from experiments in pediatric patients (5). Seven of fourteen young HTx recipients (“responders”) recovered normal peak heart rate (HR) values (maximum 203, average 177 16 beats/min) and normal HR response kinetics on submaximal constant-load exercise, as if functional heart reinnervation had occurred. Despite the likely recovery of normal oxygen delivery to exercising muscles, peak oxygen consumption, and the time constant of the V̇O2 on response to the same submaximal workload were like those found in the seven HTx recipients (“nonresponders”) with persisting markers of heart denervation, i.e., reduced and slower, respectively, compared with healthy subjects. These findings are indicative of a metabolic impairment and strengthen the importance of muscle dysfunction rather than cardiac denervation in limiting aerobic exercise after HTx.