Marion Murray Spinal Cord Research Center, Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Exp Neurol. 2022 Nov;357:114200. doi: 10.1016/j.expneurol.2022.114200. Epub 2022 Aug 8.
High-level spinal cord injury (SCI) often interrupts supraspinal regulation of sympathetic input to the heart. Although it is known that dysregulated autonomic control increases the risk for cardiac disorders, the mechanisms mediating SCI-induced arrhythmias are poorly understood. Here, we employed a rat model of complete spinal cord crush injury at the 2nd/3rd thoracic (T2/3) level to investigate cardiac rhythm disorders resulting from SCI. Rats with T9 injury and naïve animals served as two controls. Four weeks after SCI, rats were implanted with a radio-telemetric device for electrocardiogram and blood pressure monitoring. During 24-h recordings, heart rate variability in rats with T2/3 but not T9 injury exhibited a significant reduction in the time domain, and a decrease in power at low frequency but increased power at high frequency in the frequency domain which indicates reduced sympathetic and increased parasympathetic outflow to the heart. Pharmacological blockade of the sympathetic or parasympathetic branches confirmed the imbalance of cardiac autonomic control. Activation of sympatho-vagal input during the induction of autonomic dysreflexia by colorectal distention triggered various severe arrhythmic events in T2/3 injured rats. Meanwhile, intravenous infusion of the β1-adrenergic receptor agonist, dobutamine, caused greater incidence of arrhythmias in rats with T2/3 injury than naïve and T9 injured controls. Together, the results indicate that high-level SCI increases the susceptibility to developing cardiac arrhythmias likely owing to compromised autonomic homeostasis. The T2/3 crush model is appropriate for studying abnormal cardiac electrophysiology resulting from SCI.
高位脊髓损伤（SCI）常中断对心脏的交感传入的上位脊髓调节。尽管已知自主神经调节失调会增加心脏紊乱的风险，但介导 SCI 诱导性心律失常的机制尚不清楚。在这里，我们采用了 T2/3 胸段完全脊髓挤压损伤的大鼠模型来研究 SCI 引起的心律失常。T9 损伤大鼠和未损伤的动物作为两个对照。SCI 后 4 周，大鼠植入了用于心电图和血压监测的无线电遥测装置。在 24 小时记录期间，T2/3 损伤大鼠的心率变异性在时域中显著降低，在频域中低频功率降低而高频功率增加，这表明心脏的交感神经传出减少而副交感神经传出增加。交感神经或副交感神经分支的药理学阻断证实了心脏自主控制的失衡。在结直肠扩张引起的自主反射失调的诱导过程中激活交感神经-副交感神经输入，会在 T2/3 损伤大鼠中引发各种严重的心律失常事件。同时，静脉输注β1-肾上腺素能受体激动剂，多巴酚丁胺，在 T2/3 损伤大鼠中引起心律失常的发生率高于未损伤和 T9 损伤对照组。总之，这些结果表明，高位 SCI 增加了发生心律失常的易感性，可能是由于自主平衡失调。T2/3 挤压模型适合研究 SCI 引起的异常心脏电生理。
