Epicardial injection of nanoformulated calcium into cardiac ganglionic plexi suppresses autonomic nerve activity and postoperative atrial fibrillation

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • VA Medical Center
  • Virginia Commonwealth University
  • Liberty University

Details

Original languageEnglish (US)
Pages (from-to)597-605
Number of pages9
JournalHeart Rhythm
Volume16
Issue number4
StatusPublished - Apr 2019
Peer-reviewedYes

Abstract

Background: Imbalanced activation of the cardiac autonomic nervous system triggers postoperative atrial fibrillation (POAF). Neuronal calcium overload induces apoptosis. We hypothesize that epicardial injection of timed-release nanoformulated CaCl 2 (nCaCl 2 ) into left atrial ganglionic plexi (GP) modulates autonomic function and suppresses POAF. Objective: The purpose of this study was to determine whether nCaCl 2 GP therapy suppresses POAF. Methods: We used a novel canine model of POAF with implanted radiotelemetry to record nerve activity (NA) from the left stellate ganglion (SNA), left cardiac vagus nerve, and GP. At week 3, nCaCl 2 (n = 7) or vehicle control (sham; n = 3) was injected into left pulmonary vein GP (LGP), followed by right pulmonary vein GP at week 4. Atrial effective refractory period (AERP) and atrial fibrillation vulnerability (AFV) were assessed in vivo. Resting and exercise NA and heart rate (HR) were assessed before and after LGP treatment. Results: AERP decreased (P <.0001) and AFV increased (P =.008) at week 3 vs baseline. However, nCaCl 2 -LGP treatment reversed these changes and restored them to baseline after 1 week (P =.04). Subsequent nCaCl 2 –right pulmonary vein GP treatment further reduced AFV (P =.03). In contrast, AFV increased (P =.001) and AERP remained decreased (P =.01) 1 week after sham-LGP treatment vs baseline. nCaCl 2 -LGP treatment reduced NA from GP (P <.02) and NA from the left cardiac vagus nerve (P <.05) and increased SNA (P <.02). Despite increased SNA, HR was decreased (P <.01) with loss of HR-SNA correlation (R = 0.62). After sham-LGP treatment, NA was unchanged and HR-SNA remained correlated (R = 0.95). Histology confirmed nCaCl 2 -GP colocalization, apoptosis, and loss of immunoreactivity in nCaCl 2 -treated somas. Conclusion: Epicardial injection of nCaCl 2 into left atrial GP induced neuroapoptosis and modulated autonomic function. This reversed a postoperative reduction in AERP and suppressed POAF.

    Research areas

  • Animal model, Autonomics, Cardiac surgery, Neural modulation, Postoperative atrial fibrillation