Sympathetic Rhythmicity in Cardiac Transplant Recipients

Abstract

Background-Variability of R-R interval and muscle sympathetic nerve activity (MSNA) occurs predominantly at a low frequency (LF, Ϯ0.1 Hz) and a high frequency (HF, Ϯ0.25 Hz) in normal humans. Increased sympathetic drive in normal humans is associated with an increased LF component of the R-R interval and MSNA. Patients with severe heart failure have high sympathetic activity but decreased or absent LF power of both R-R and MSNA. We tested the hypothesis that this dysfunction in autonomic modulation in heart failure can be reversed by heart transplantation. Methods and Results-We performed spectral analysis of resting MSNA, R-R interval, and respiration in 9 patients with heart transplants, 9 chronic heart failure patients, and 9 normal control subjects, all closely matched for age, sex, and body mass index. MSNA (bursts per minute) was higher in patients with heart transplants (74Ϯ3) than either patients with heart failure (56Ϯ6) or normal subjects (40Ϯ4) (PϽ0.001). LF variability in the R-R interval was reduced in both heart transplant recipients and heart failure patients compared with the control subjects (PϽ0.01). The LF variability in MSNA was also nearly absent in the heart failure patients (PϽ0.01). However, the LF and HF oscillations in MSNA in patients with heart transplants were comparable to those evident in the control subjects. Conclusions-Cardiac transplantation does not reduce MSNA. However, LF oscillations in sympathetic activity are restored after transplantation such that the MSNA oscillatory profile is similar to that observed in normal subjects.

Differential Characteristics of Neural Circulatory Control

“…The other component is described as the LF oscillation and has a center frequency of about 0.10 Hz but can vary considerably (from 0.03 to 0.15 Hz). 2,8,9,13,15,17 In this study, the LF and HF components were expressed in normalized units (nu). The normalized LF and HF units were obtained by calculating the absolute variability of each LF and HF component as a percentage of the total power after subtracting the power of the very LF component (frequencies below nominal 0.03 Hz).…”

“…The normalized LF and HF units were obtained by calculating the absolute variability of each LF and HF component as a percentage of the total power after subtracting the power of the very LF component (frequencies below nominal 0.03 Hz). 2,8,9,13,15,17 The amount of linear coupling between variability in MSNA and RR was determined by means of a coherence function. 16,18 This function varies between 0 and 1 and can be compared with the squared correlation coefficient in a linear regression equation, because it indicates the amount of variance in RR linearly related to the variance in sympathetic nerve traffic.…”

“…In previous studies, we have shown a restoration of LF oscillations in MSNA after heart transplantation. 2 Partial cardiac reinnervation was sug- Electrocardiographic activity, sympathetic nerve activity, and respiratory activity in a short-term (9 months after heart transplantation, left) and a long-term (163 months after transplantation, right) heart transplant recipient (HTR). MSNA is markedly elevated in the long-term transplant patient.…”

“…[1][2][3] These patients may also manifest slower oscillations in RR (0.03 to 0.15 Hz, lowfrequency [LF]), which are not mediated by the mechanical effects of respiration. These LF oscillations are a marker of functional sympathetic reinnervation of the sinus node, because they increase in amplitude during sinusoidal neck suction and are attenuated by ␤-blockade.…”

“…7 Previous studies in control subjects and patients with cardiac transplants have demonstrated that direct recordings of sympathetic nerve traffic (muscle sympathetic nerve activity [MSNA]) exhibit LF and HF oscillatory components almost identical to those present in heart-rate variability. 2,8,9 High sympathetic drive in transplant recipients has been linked to cyclosporine use and cardiac denervation. 10 There are no data indicating the effects of duration of transplantation on sympathetic activity.…”