The present study was performed to test whether beat-to-beat cardiovascular control in cardiac allograft recipients resides in cholinergic and/or adrenergic nerves that are intrinsic to the heart. 2. Heart rate (HR) fluctuations synchronous with respiration during spontaneous, double tidal volume and metronome-synchronized breathing were quantified in 13 human heart transplant recipients. We also examined the effects of sequential cholinergic and beta-adrenoceptor (combined) autonomic blockade on respiratory sinus arrhythmia (RSA). We computed RSA amplitude and the correlation between respiration and changes in HR (cardiopulmonary synchronization; CPS). Group means were compared using repeated-measures analysis of variance. Transplant recipients served as their own controls. 3. In the basal state, moderate RSA amplitude and CPS were observed. During cholinergic and combined blockade, we observed no significant change in RSA amplitude, whereas CPS increased significantly during combined blockade (P < 0.05). The amplitude of RSA increased during respiration at double baseline tidal volume, but not at any of the other breathing manoeuvres (P < 0.01). In contrast, CPS increased significantly during both patterned breathing manoeuvres. No significant correlation was seen between mean right atrial pressure and RSA amplitude. In 23% of subjects with low CPS, HR oscillated with arterial pressure. These oscillations were independent of respiration. During all three patterns of respiration, a significant inverse correlation was observed between CPS and pulse pressure (r = -0.53 to -0.73). Thus, as the amplitude of pulse pressure increased, respiration accounted for a smaller percentage of HR variation. 4. In conclusion, RSA persists and the magnitude of CPS increases following combined autonomic blockade. These studies suggest that while RSA after cardiac transplantation is not cholinergically or adrenergically mediated, it may be related to mechanical stretch of the sinus node caused by changes in intrathoracic pressure and perfusion pressure.
