Shibuya M, Suzuki Y, Takayasu M, Asano T, Harada T, Ikegaki I, Satoh S, Hidaka H
Department of Neurosurgery, Nagoya University, Japan.
Acta Neurochir (Wien). 1988;90(1-2):53-9. doi: 10.1007/BF01541267.
The effectiveness of calcium antagonists on a chronic cerebral vasospasm after an SAH is still under debate. Calcium channel blockers such as nimodipine, nifedipine etc. can dilate spastic arteries by intrathecal administration, but not by systemic (iv or po) use. HA 1077 is a novel and potent calcium antagonist vasodilator which is considered to act by employing different mechanisms from the usual calcium channel blockers since it inhibits 1. calcium ionophore A 23187 induced contraction in arterial strips and 2. phenylephrine induced contraction in calcium free media, suggesting that its site of action is in the intracellular space. HA 1077 is water soluble and relatively stable in light. In the present study, the efficacy of HA 1077 was evaluated on dogs by using the spiral arterial strips in vitro and by angiography in vivo. In the arterial strips from the control dogs, a 50% relaxation of KCl (15 mM) induced contraction was obtained by a 10(-6) M HA 1077 for the "intracranial" basilar and middle cerebral arteries, while a 10(-5) M was needed to obtain the same effect for the "extracranial" common carotid and vertebral arteries, indicating that HA 1077 is more effective for the intracranial arteries. A vasospasm was produced by the "two haemorrhage" model of Varsos et al. The average angiographic diameter of the basilar artery was reduced to 60% of the control on SAH day 7. Intravenous infusion of HA 1077 (0.5-3 mg/kg/30 min) significantly dilated the spastic basilar artery (up to 20-30%), for over 2 hours. A fall in the systemic BP remained less than 20% during this time.(ABSTRACT TRUNCATED AT 250 WORDS)
钙拮抗剂对蛛网膜下腔出血（SAH）后慢性脑血管痉挛的疗效仍存在争议。钙通道阻滞剂如尼莫地平、硝苯地平等，鞘内给药可扩张痉挛动脉，但全身（静脉或口服）用药则无效。HA 1077是一种新型强效钙拮抗剂血管扩张剂，因其抑制1. 钙离子载体A 23187诱导的动脉条收缩和2. 去氧肾上腺素在无钙培养基中诱导的收缩，被认为其作用机制与常用钙通道阻滞剂不同，提示其作用位点在细胞内空间。HA 1077水溶性好，在光照下相对稳定。在本研究中，通过体外使用螺旋动脉条和体内血管造影术评估了HA 1077对犬的疗效。在对照犬的动脉条中，10（-6）M的HA 1077可使“颅内”基底动脉和大脑中动脉对氯化钾（15 mM）诱导的收缩产生50%的舒张，而“颅外”颈总动脉和椎动脉则需要10（-5）M才能达到相同效果，表明HA 1077对颅内动脉更有效。采用Varsos等人的“两次出血”模型诱发血管痉挛。在SAH第7天，基底动脉的平均血管造影直径降至对照值的60%。静脉输注HA 1077（0.5 - 3 mg/kg/30 min）可使痉挛的基底动脉显著扩张（达20 - 30%），持续超过2小时。在此期间，全身血压下降保持在20%以内。（摘要截断于250字）
