Korean Circ J.  2016 Mar;46(2):197-206. 10.4070/kcj.2016.46.2.197.

Early Parasympathetic Reinnervation Is Not Related to Reconnection of Major Branches of the Vagus Nerve after Heart Transplantation

• Lee SR
• Kang DY
• Cho Y
• Cho HJ
• Lee HY
• Choi EK
• Oh S

• KMID: 2344471
• DOI: http://doi.org/10.4070/kcj.2016.46.2.197

Abstract

BACKGROUND AND OBJECTIVES
Bicaval heart transplantation (HTx) may promote parasympathetic reinnervation. However, the prevalence and timing of reinnervation have not been fully investigated. Heart rate variability (HRV) and direct vagal stimulation were used to evaluate the presence of parasympathetic reinnervation after bicaval HTx.
SUBJECTS AND METHODS
A total of 21 patients (time after HTx 0.52-4.41 years, mean 1.8±1.2 years) who received a bicaval HTx was enrolled. Reinnervation was evaluated using HRV values from 24-hour Holter recordings. A cross-sectional analysis of the HRV at 0.5-1, 1-2, and >2 years after HTx was performed. We also applied high-frequency electrical stimulation (16.7 Hz, 1 msec pulse width, ≤10 V) to the cardiac branches of the vagus nerve at the level of the superior vena cava in eight patients at 6 and 12 months after HTx.
RESULTS
The degree of parasympathetic reinnervation corresponded to the time after HTx. The HRV analysis revealed that the root mean square of the successive differences between consecutive RR-intervals (RMSSD) and high-frequency power were significantly higher during the late period (>2 years) compared with the early period (0.5-1 year) after HTx. None of the eight patients who underwent direct vagal stimulation responded during the stimulation at 6 and 12 months, whereas incremental trends in HRV parameters were observed, which indicated that parasympathetic reinnervation began within 1 year after HTx.
CONCLUSION
Parasympathetic reinnervation seemed to begin in the early period (<1 year) after bicaval HTx. Reconnection of major branches of the vagus nerve may not be related to early reinnervation.

Keyword

Heart transplantation; Reinnervation; Vagus nerve; Parasympathetic

MeSH Terms

Cross-Sectional Studies
Electric Stimulation
Heart Rate
Heart Transplantation*
Heart*
Humans
Prevalence
Vagus Nerve*
Vena Cava, Superior

Figure

• 

  Fig. 1 Illustration of the location of the right vagus nerve and direct vagal stimulation. (A) The right vagus nerve crosses anterior to the right subclavian artery, runs posterior to the SVC, and contributes to the cardiac, pulmonary, and esophageal plexuses. (B) A steerable quadri-polar catheter was placed in the SVC, just above the suture line, for the stimulation of the cardiac branches of the recipient's right vagus nerve. SVC: superior vena cava, IVC: inferior vena cava.

• 

  Fig. 2 Scatterplots showing the significant positive correlations between the time after HTx and heart rate variability parameters, including LF (A), HF (B), ASDNN (C) and RMSSD (D). The vertical dot lines divide the subjects into early (0.5-1 year), intermediate (1-2 years) and late (>2 years) groups after HTx. HTx: heart transplantation, LF: low-frequency component, HF: high-frequency component, ASDNN: average of all 5-minute standard deviations of the NN interval, RMSSD: square root of the difference between consecutive RR-intervals.

• 

  Fig. 3 Incremental changes in the HRV analysis of parasympathetic parameters. RMSSD (A) and HF (B) were significantly higher during the late period (>2 years) compared with the early period (0.5-1 year) after HTx. *p<0.017 indicates the presence of a statistically significant difference between two groups in the post-hoc analysis. HRV: heart rate variability, RMSSD: square root of the difference between consecutive RR-intervals, HF: high-frequency component, HTx: heart transplantation.

• 

  Fig. 4 Serial assessment of HRV at 6 and 12 months after heart transplantation. (A) LF, (B) HF, (C) ASDNN, and (D) RMSSD. There were no statistically significant changes between 6 and 12 months, likely because of the small sample size. However, modest incremental changes were observed (p<0.05 indicates a statistically significant result). HRV: heart rate variability, LF: low-frequency component, HF: high-frequency component, ASDNN: average of all 5-minute standard deviations of the NN interval, RMSSD: square root of the difference between consecutive RR-intervals.

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