经心外膜注射纳米钙制剂至心脏神经丛可抑制自主神经活动和术后心房颤动。
Epicardial injection of nanoformulated calcium into cardiac ganglionic plexi suppresses autonomic nerve activity and postoperative atrial fibrillation.
机构信息
Electrophysiology Section, Division of Cardiology, Hunter Holmes McGuire VAMC, Richmond, Virginia; Pauley Heart Center, Virginia Commonwealth University Medical Center, Richmond, Virginia.
Liberty University College of Osteopathic Medicine, Lynchburg, Virginia.
出版信息
Heart Rhythm. 2019 Apr;16(4):597-605. doi: 10.1016/j.hrthm.2018.10.014.
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 (nCaCl) into left atrial ganglionic plexi (GP) modulates autonomic function and suppresses POAF.
OBJECTIVE
The purpose of this study was to determine whether nCaCl 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 (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-LGP treatment reversed these changes and restored them to baseline after 1 week (P = .04). Subsequent nCaCl-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-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-GP colocalization, apoptosis, and loss of immunoreactivity in nCaCl-treated somas.
CONCLUSION
Epicardial injection of nCaCl into left atrial GP induced neuroapoptosis and modulated autonomic function. This reversed a postoperative reduction in AERP and suppressed POAF.
背景
心脏自主神经系统的失衡激活会引发术后心房颤动（POAF）。神经元钙超载会导致细胞凋亡。我们假设在心外膜上左心房神经节丛（GP）注射定时释放纳米形式氯化钙（nCaCl）可以调节自主神经功能并抑制 POAF。
目的
本研究旨在确定 nCaCl-GP 治疗是否可以抑制 POAF。
方法
我们使用一种新型的植入式无线电遥测犬 POAF 模型来记录左侧星状神经节（SNA）、左侧心迷走神经和 GP 的神经活动（NA）。在第 3 周，nCaCl（n = 7）或载体对照（假手术；n = 3）被注入左肺静脉 GP（LGP），然后在第 4 周注入右肺静脉 GP。在体内评估心房有效不应期（AERP）和心房颤动易损性（AFV）。在 LGP 治疗前后评估静息和运动时的 NA 和心率（HR）。
结果
与基线相比，第 3 周 AERP 降低（P <.0001），AFV 增加（P =.008）。然而，nCaCl-LGP 治疗逆转了这些变化，并在 1 周后恢复到基线（P =.04）。随后的 nCaCl-右肺静脉 GP 治疗进一步降低了 AFV（P =.03）。相比之下，与基线相比，假手术-LGP 治疗 1 周后 AFV 增加（P =.001），AERP 持续降低（P =.01）。nCaCl-LGP 治疗降低了 GP（P <.02）和左侧心迷走神经（P <.05）的 NA，并增加了 SNA（P <.02）。尽管 SNA 增加，但 HR 降低（P <.01），且 HR-SNA 相关性丧失（R = 0.62）。在假手术-LGP 治疗后，NA 没有变化，HR-SNA 仍然相关（R = 0.95）。组织学证实 nCaCl-GP 共定位、神经元凋亡以及 nCaCl 处理后的 soma 免疫反应丧失。
结论
在心外膜上左心房 GP 注射 nCaCl 诱导神经细胞凋亡并调节自主神经功能。这逆转了术后 AERP 的降低并抑制了 POAF。
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