Early Signs of Sinoatrial Reinnervation in the Transplanted Heart

Abstract

Background. Heart transplantation (HTx) surgically transects all connections to the heart, including the autonomic nerves. We prospectively examined signs, timing and consequences of early sympathetic and parasympathetic sinoatrial reinnervation, as well as explored indirect evidence of afferent cardiopulmonary reinnervation. Methods. Fifty HTx recipients were assessed at 2.5, 6, and 12 mo after HTx. For comparison, 50 healthy controls were examined once. Continuous, noninvasive recordings of hemodynamic variables and heart rate variability indices were performed at supine rest, 0.2 Hz controlled breathing, 60° head-up-tilt, during the Valsalva maneuver and during handgrip isometric exercise. Results. In HTx recipients, supine low-frequency heart rate variability gradually increased; supine high-frequency variability did not change; heart rate variability indices during controlled breathing remained unaltered; heart rate responses during tilt and isometric exercise gradually increased; the tachycardia response during Valsalva maneuver increased, while the bradycardia response remained unchanged; and indices of baroreflex sensitivity improved. Responses remained low compared to healthy controls. A negative correlation between indices of preload and heart rate response during head-up tilt emerged at 12 mo. Conclusions. Results suggest that sympathetic reinnervation of the sinoatrial node starts within 6 mo after HTx and strengthens during the first year. No evidence of early parasympathetic reinnervation was found. Indirect signs of afferent reinnervation of cardiopulmonary low-pressure baroreceptors emerged at 12 mo. Better sympathetic sinoatrial control improved heart rate responsiveness to orthostatic challenge and isometric exercise, as well as heart rate buffering of blood pressure fluctuations.

Functional evidence of low-pressure cardiopulmonary baroreceptor reinnervation 1 year after heart transplantation

“…The gradual normalization of the HR response to light orthostatic challenge during the follow-up period directly suggests that both the afferent cardiopulmonary and efferent sympathetic limbs of this reflex loop are intact. The efferent sympathetic reinnervation of the sinus node demonstrated here has been reported elsewhere (Christensen et al 2020); however, the afferent reinnervation of cardiopulmonary receptors that re-establishes a normal reflex loop is a novel finding of the present study.…”

“…The short epoch (3 seconds length) during handgrip was chosen in order to obtain the most extreme (maximal) value in each individual (Nygaard et al 2019). Likewise, for the Valsalva maneuver, HR response was defined as the largest positive (tachycardia) and negative (bradycardia) change from baseline (ie., median value of the last 30 seconds before initiation of the maneuver) (Christensen et al 2020). SBP fall was taken as the largest negative change from baseline during the maneuver, whereas SBP overshoot was defined as the largest positive difference between baseline and the recovery phase immediately after the maneuver.…”

“…The autonomic cardiovascular assessment encompassed the following tests: 1) supine rest (5 minutes); 2) 20 o head-up tilt (15 minutes); 3) Valsalva maneuver (15 seconds, airway pressure of 40 mmHg, repeated twice); 4) isometric exercise (60 seconds, handgrip of 30% maximal voluntary force, repeated twice). A detailed description is provided elsewhere (Nygaard et al 2019;Christensen et al 2020).…”

“…Ample evidence suggests that reinnervation might occur over time. In particular, efferent sympathetic reinnervation of the sinus node has been implicated in several studies (Peiss et al 1966;Wilson et al 1991;Estorch et al 1999;Uberfuhr et al 2000;Christensen et al 2020). However, the extent of reinnervationas well as the functional consequences of both the denervation and the reinnervation processesremain largely unknown.…”

Role of heart rate variability and regulatory-adaptive status index in predicting the heart transplant rejection

“…Анализ ряда работ зарубежных авторов показал, что в более ранние сроки наблюдаются признаки симпатической реиннервации (от 5-6 мес. до 1 года после операции), а парасимпатическая требует более длительного послеоперационного периода и регистрируется на втором году после операции [8][9][10]. По данным других источников, в наиболее длительном исследовании, проведенном Beckers F, et al, положительная динамика ВРС отмечена через 2 года после операции, а увеличение мощности LF и, соответственно, наличие симпатической реиннервации трансплантата -через 4 года, но значения LF ниже, чем у здоровых [11].…”