Background-Reappearance of low-frequency (LF) (Ϯ0.10 Hz) oscillations in RR interval (RR) after cardiac transplantation is indicative of sympathetic efferent reinnervation. We hypothesized that restored LF oscillations in RR in heart transplant recipients (HTRs) are linked to oscillations in muscle sympathetic nerve traffic (MSNA). Methods and Results-RR, RR variability, and MSNA were recorded 5Ϯ2 months (nϭ7, short-term HTRs) and 138Ϯ8 months (nϭ7, long-term HTRs) after heart transplantation and compared with matched hypertensive patients (nϭ7). A coherence function determined the coupling between LF oscillations in MSNA and RR. RR variance did not differ between short-term and long-term HTRs. However, LF variability was only 1Ϯ0.5 ms 2 in the short-term HTRs but was 15Ϯ8 ms 2 in the long-term HTRs (PϽ0.05). Normalized LF variability was also higher in the long-term HTRs (40Ϯ14 normalized unites) versus the short-term HTRs (6Ϯ3 normalized united, PϽ0.05) but did not differ from the LF variability of the hypertensive patients. Long-term HTRs were taking less cyclosporine (PϽ0.01) but had higher MSNA than the short-term HTRs (62Ϯ7 versus 31Ϯ7 burst/min, respectively, PϽ0.05). Coherence between LF oscillations in MSNA and RR was similar in the long-term HTRs (0.59Ϯ0.11) and the hypertensive patients (0.60Ϯ0.07) and was 3-fold greater than in the short-term HTRs (0.20Ϯ0.06, PϽ0.05). Conclusions-Cardiac reinnervation after long-term heart transplantation is characterized by a restoration of the coherence between LF oscillations in RR and MSNA. Higher MSNA in long-term than in short-term HTRs suggests that time elapsed after cardiac transplantation may be a major determinant of sympathetic excitation in heart transplant recipients.

The relative contributions of a central neural oscillator and of the delay in alpha-adrenergic transmission within the baroreflex loop in the predominance of low-frequency (LF) cardiovascular variability during sympathetic activation in humans are unclear. We measured R-R interval (RR), muscle sympathetic nerve activity (MSNA), blood pressure (BP), and their variability in 10 normal subjects during sympathetic activation achieved by BP lowering with sodium nitroprusside (SNP) and alpha-adrenergic blockade using phentolamine. SNP and phentolamine induced comparable reductions in BP (P > 0.25). Despite tachycardia and sympathetic activation with both SNP and phentolamine, LF variability in RR, MSNA, and BP increased during SNP and decreased during phentolamine (SNP: RR +20 +/- 6%, MSNA +3 +/- 5%, systolic BP +9 +/- 6%, diastolic BP +7 +/- 5%; phentolamine: RR -2 +/- 7%, MSNA -34 +/- 6%, systolic BP -16 +/- 8%, diastolic BP -13 +/- 4%, P < 0.05 except systolic BP, where P = 0.09). Thus LF variability is reduced when sympathetic activation is induced by alpha-adrenergic blockade. This suggests that alpha-adrenergic transmission within the baroreflex loop may contribute importantly to the predominance of LF cardiovascular variability associated with sympathetic excitation in humans.