Non-Respiratory Components of Heart Rate Variability in Heart Transplant Recipients: Evidence of Autonomic Reinnervation?

Abstract

1. Although the high-frequency fluctuations in R—R interval (respiratory sinus arrhythmia) observed in heart transplant recipients are not a reliable marker of reinnervation because of a previously shown direct mechanical effect of breathing, the presence of a non-respiration-related low-frequency oscillation reflects rhythms generated outside the heart, and thus could be neurally mediated. 2. To evaluate the presence of reinnervation, the spontaneous variability in R—R interval was investigated, supine and after passive tilting, in 23 heart transplant recipients (age 43 years, range 23–64 years) and in 25 normotensive control subjects by autoregressive spectral analysis of low- and high-frequency spontaneous fluctuations in R—R interval and respiration. The response of R—R interval to amyl nitrite inhalation was also evaluated in five heart transplant recipients and eight control subjects. 3. Detectable low-frequency oscillations, unrelated to respiration, were present in 13/23 heart transplant recipients, particularly in those who were transplanted at least 20 months earlier (11/14). The natural logarithm of the power of low-frequency fluctuations was markedly lower than in control subjects (0.75 ± 0.21 versus 5.62 ± 0.20 ms2, P < 0.001). The low-frequency but not the high-frequency fluctuations correlated with time since transplantation (r = 0.44, P < 0.05). The subjects with low-frequency fluctuations showed a sudden decrease in R—R interval with amyl nitrite linearly related to the decrease in mean blood pressure (r ≧ 0.94). The slopes obtained in these heart transplant recipients were comparable (although of lower values) with those obtained in control subjects. The subjects with no low-frequency fluctuations showed no change in R—R interval despite a similar reduction in blood pressure. 4. Twenty months after transplantation signs of functional (reflex) reinnervation can be found in most heart transplant recipients.