Background: Spinal cord injury (SCI) impairs the cardiovascular responses to postural challenge, leading to the development of orthostatic hypotension (OH). Here, we apply lower body negative pressure (LBNP) to rodents with high-level SCI to demonstrate the usefulness of LBNP as a model for experimental OH studies and to explore the effect of simulated OH on cardiovascular and cerebrovascular function following SCI. Methods: 32 male Wistar rats were subjected to a sham or T3-SCI surgery and survived into the chronic period post-injury (i.e., 8 weeks). Cardiac function was tracked via ultrasound pre-to-post SCI to demonstrate the clinical utility of our model. At study termination, we conducted left-ventricular (LV) catheterization and insonated the middle cerebral artery to investigate the hemodynamic, cardiac, and cerebrovascular response to a mild dose of LBNP that is sufficient to mimic clinically defined OH in rats with T3-SCI but not SHAM animals. Results: In response to mimicked OH, there was a greater decline in stroke volume, cardiac output, maximal LV pressure, and blood pressure in SCI compared to SHAM (p < 0.034), while heart rate was increased in SHAM but decreased in SCI (p < 0.029). SCI animals also had an exaggerated reduction in peak, minimum and mean middle cerebral artery flow, for a given change in blood pressure, in response to LBNP (p < 0.033), implying impaired dynamic cerebral autoregulation. Conclusion: Using a preclinical SCI model of OH, we demonstrate that complete high thoracic SCI impairs the cardiac response to OH and disrupts dynamic cerebral autoregulation.

中文翻译：

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实验性高位胸脊髓损伤损害大鼠对直立性挑战的心脑血管反应

背景：脊髓损伤 (SCI) 会损害心血管对姿势挑战的反应，导致直立性低血压 (OH) 的发展。在这里，我们将下体负压 (LBNP) 应用于具有高水平 SCI 的啮齿动物，以证明 LBNP 作为实验性 OH 研究模型的有用性，并探索模拟 OH 对 SCI 后心脑血管功能的影响。方法：32 只雄性 Wistar 大鼠接受了假手术或 T3-SCI 手术，并存活到受伤后的慢性期（即 8 周）。通过超声前后 SCI 跟踪心脏功能，以证明我们模型的临床效用。在研究结束时，我们进行了左心室 (LV) 导管插入术并对大脑中动脉进行声波检查以研究血流动力学、心脏、和脑血管对轻度 LBNP 的反应，足以模拟 T3-SCI 大鼠但不是 SHAM 动物的临床定义的 OH。结果：响应模拟 OH，与 SHAM 相比，SCI 患者的每搏输出量、心输出量、最大 LV 压力和血压下降幅度更大（p < 0.034），而 SHAM 患者的心率增加但 SCI 患者的心率下降（ p < 0.029)。对于 LBNP 给定的血压变化，SCI 动物的峰值、最小和平均大脑中动脉流量也有明显降低（p < 0.033），这意味着动态大脑自动调节受损。结论：使用 OH 的临床前 SCI 模型，我们证明完全高位胸 SCI 会损害心脏对 OH 的反应并破坏动态大脑自动调节。