Department of Gerontology, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu, China.
Department of Geriatrics, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, China.
Pharmacology. 2024;109(5):253-265. doi: 10.1159/000538997. Epub 2024 Apr 22.
Ventricular arrhythmia is commonly provoked by acute cardiac ischemia through sympathetic exaggeration and is often resistant to anti-arrhythmic therapies. Thoracic epidural anesthesia has been reported to terminate fatal ventricular arrhythmia; however, its underlying mechanism is unknown.
Rats were randomly divided into four groups: sham, sham plus bupivacaine, ischemia/reperfusion (IR), and IR plus bupivacaine groups. Bupivacaine (1 mg/mL, 0.05 mL/100 g body weight) was injected intrathecally into the L5-L6 intervertebral space prior to establishing a myocardial IR rat model. Thereafter, cardiac arrhythmia, cardiac function, myocardial injury, and electrical activities of the heart and spinal cord were evaluated.
Intrathecal bupivacaine inhibited spinal neural activity, improved heart rate variability, reduced ventricular arrhythmia score, and ameliorated cardiac dysfunction in IR rats. Furthermore, intrathecal bupivacaine attenuated cardiac injury and myocardial apoptosis and regulated cardiomyocyte autophagy and connexin-43 distribution during myocardial IR.
Our results indicate that intrathecal bupivacaine blunts spinal neural activity to prevent cardiac arrhythmia and dysfunction induced by IR and that this anti-arrhythmic activity may be associated with regulation of autonomic balance, myocardial apoptosis and autophagy, and cardiac gap junction function.
室性心律失常通常通过交感神经亢进引起急性心肌缺血,并且常常对抗心律失常治疗有抗性。胸段硬膜外麻醉已被报道可终止致命性室性心律失常;然而,其潜在机制尚不清楚。
大鼠随机分为四组:假手术组、假手术加布比卡因组、缺血/再灌注(IR)组和 IR 加布比卡因组。在建立心肌 IR 大鼠模型之前,将布比卡因(1mg/mL,0.05mL/100g 体重)鞘内注射到 L5-L6 椎间空间。此后,评估心律失常、心功能、心肌损伤以及心脏和脊髓的电活动。
鞘内布比卡因抑制脊髓神经活动,改善心率变异性,降低 IR 大鼠的室性心律失常评分,并改善心功能障碍。此外,鞘内布比卡因减轻了心肌损伤和心肌细胞凋亡,并调节了心肌 IR 期间的心肌细胞自噬和连接蛋白 43 分布。
我们的结果表明,鞘内布比卡因减弱脊髓神经活动以预防 IR 引起的心律失常和心功能障碍,这种抗心律失常活性可能与自主平衡调节、心肌凋亡和自噬以及心脏缝隙连接功能有关。