The effects of HA compound calcium antagonists on delayed cerebral vasospasm in dogs.
The effects of HA compound calcium antagonists on delayed cerebral vasospasm in dogs.
复制标题
HA复合钙拮抗剂对犬迟发性脑血管痉挛的作用。
作者：
M. Takayasu;Y. Suzuki;M. Shibuya;T. Asano;M. Kanamori;T. Okada;N. Kageyama;H. Hidaka
作者研究了HA化合物HA 1004（N-（2-胍基乙基）-5-异喹啉磺酰胺）和HA 1077（1-（5-异喹啉磺酰基）高哌嗪）（细胞内钙拮抗剂）对蛛网膜下腔出血（SAH）所致迟发性脑血管痉挛的影响。将这些化合物的作用模式与更常用的钙进入阻滞剂进行比较。钙离子载体A23187（4.8 × 10（-6）M）诱导的犬基底动脉条收缩可被HA化合物（10（-5）M）完全拮抗，但不能被进入阻断钙拮抗剂尼卡地平、地尔硫卓和维拉帕米（10（-5）M）拮抗，表明HA化合物的作用不同。采用“二次出血”犬模型，诱发迟发性脑血管痉挛。血管痉挛的程度和HA化合物的作用通过血管造影确定。在SAH第7天，在每只犬中观察到显著的血管痉挛。基底动脉直径减小至SAH前（第1天）获得的对照值的59% ± 2%（平均值±标准误差）。HA 1004静脉给药在3和10 mg/kg剂量下分别引起基底动脉轻度扩张10%和11%;然而，HA 1077在相同剂量下分别引起19%和27%的更显著扩张。这两种药物在剂量为3和10 mg/kg时分别将平均动脉血压降低至约80%和50%。脑池内给予HA化合物（6 mg）完全逆转了脑血管痉挛，对血压没有太大影响。HA复合物组的细胞内钙拮抗剂似乎是治疗顽固性脑血管痉挛的有前途的药物。
The authors have examined the effects of the HA compounds HA1004(N-(2-guanidinoethyl)-5-isoquinolinesulfonamide) and HA 1077(1-(5-isoquinolinesulfonyl)homopiperazine), which are intracellular calcium antagonists, on delayed cerebral vasospasm from subarachnoid hemorrhage (SAH). The modes of action of these compounds were compared with those of the more commonly used calcium entry blockers. Calcium ionophore A23187 (4.8 X 10(-6) M)-induced contraction of a canine basilar artery strip was completely antagonized by the HA compounds (10(-5) M) but not by the entry-blocking calcium antagonists nicardipine, diltiazem, and verapamil (10(-5) M), suggesting that the HA compounds act differently. Delayed cerebral vasospasm was induced by a "two-hemorrhage" canine model. The magnitude of the vasospasm and the effects of the HA compounds were determined angiographically. On SAH Day 7, a significant vasospasm was observed in every dog. The diameter of the basilar artery had diminished to 59% +/- 2% (mean +/- standard error) of the control value obtained before SAH (on Day 1). The intravenous administration of HA 1004 caused a mild dilation of the basilar artery of 10% and 11% at doses of 3 and 10 mg/kg, respectively; however, HA 1077 produced a more marked dilation of 19% and 27%, respectively, at the same doses. Both of these drugs lowered mean arterial blood pressure to about 80% and 50% at doses of 3 and 10 mg/kg, respectively. Intracisternal administration of the HA compounds (6 mg) completely reversed cerebral vasospasm without much effect on the blood pressure. The intracellular calcium antagonists of the HA compound group appear to be promising agents for the treatment of intractable cerebral vasospasm.