Johnson S H, Kraimer J M, Graeber G M
Division of Surgery, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, DC.
Stroke. 1993 Oct;24(10):1547-53. doi: 10.1161/01.str.24.10.1547.
The lipophilic calcium channel antagonist flunarizine has been demonstrated to be neuroprotective in several models of cerebral ischemia. Ischemic spinal cord injury may have a similar pathophysiology and hence may respond in a similar fashion. This study was designed to investigate the effects of pretreatment with flunarizine on systemic hemodynamics, spinal cord blood flow, and neurological recovery in a rabbit model of ischemic spinal cord injury.
New Zealand White rabbits were anesthetized with ketamine and xylazine and instrumented for systemic blood pressure monitoring and spinal cord blood flow measurements using the microsphere method. After pretreatment with flunarizine or vehicle, ischemic spinal cord injury was created selectively in the caudal regions of the spinal cord by cross-clamping the abdominal aorta for a period of 25 minutes. Spinal cord blood flow was measured before, during, and 15 minutes after cross-clamp removal. Animals were allowed to recover and were graded neurologically at 18 and 24 hours after ischemia.
Flunarizine injection was associated with hypotension that was both transient and dose related. Animals pretreated with flunarizine 0.4 mg/kg had significantly improved neurological recovery scores at 18 hours after ischemia (P = .017) compared with vehicle controls. At 24 hours this effect was lessened (P = .095); however, 60% of flunarizine-treated animals retained their ability to hop, whereas all of the vehicle-treated animals were nonambulatory.
Flunarizine has a protective effect on neurological recovery after experimental ischemic spinal cord injury. The therapeutic window is narrow, and dosing is limited by untoward hypotension. The mechanism of protection likely involves inhibition of pathological cytosolic calcium accumulation rather than a direct effect on vascular smooth muscle.
亲脂性钙通道拮抗剂氟桂利嗪已在多种脑缺血模型中被证明具有神经保护作用。缺血性脊髓损伤可能具有相似的病理生理学，因此可能有类似的反应。本研究旨在探讨氟桂利嗪预处理对缺血性脊髓损伤兔模型全身血流动力学、脊髓血流量及神经功能恢复的影响。
用氯胺酮和赛拉嗪麻醉新西兰白兔，使用微球法监测全身血压并测量脊髓血流量。用氟桂利嗪或赋形剂预处理后，通过夹闭腹主动脉25分钟在脊髓尾端区域选择性造成缺血性脊髓损伤。在夹闭去除前、夹闭期间及夹闭去除后15分钟测量脊髓血流量。让动物恢复，并在缺血后18小时和24小时进行神经功能评分。
注射氟桂利嗪与短暂性且与剂量相关的低血压有关。与赋形剂对照组相比，用0.4mg/kg氟桂利嗪预处理的动物在缺血后18小时神经功能恢复评分显著改善（P = 0.017）。在24小时时这种作用减弱（P = 0.095）；然而，60%接受氟桂利嗪治疗的动物仍保持跳跃能力，而所有接受赋形剂治疗的动物均不能行走。
氟桂利嗪对实验性缺血性脊髓损伤后的神经功能恢复有保护作用。治疗窗较窄，给药受不良低血压限制。保护机制可能涉及抑制病理性胞浆钙积聚，而非对血管平滑肌的直接作用。
