Thromboxane A2 synthetase inhibitor failed to ameliorate the arterial narrowing during the chronic phase of cerebral vasospasm

• Published in: Life sciences (1973) Vol. 61; no. 14; pp. 1371 - 1377
• Main Authors: Toshima, Yoshinori, Satoh, Shin-ichi, Ikegaki, Ichiro, Asano, Toshio, Suzuki, Yoshio, Shibuya, Masato
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 1997
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology; Animals; Cerebral Hemorrhage - drug therapy; cerebral vasospasm; dog; Dogs; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; fasudil; Female; Ischemic Attack, Transient - drug therapy; Ischemic Attack, Transient - physiopathology; Male; Methacrylates - pharmacology; ozagrel; protein kinase; Protein Kinase Inhibitors; thromboxane A2; Thromboxane-A Synthase - antagonists & inhibitors; Vasoconstriction - drug effects; ozagrel; cerebral vasospasm; dog; fasudil; protein kinase; thromboxane A2
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(97)00682-6

To determine the pathogenetic mechanism underlying the maintenance of arterial narrowing during the chronic phase of cerebral vasospasm caused by subarachnoid hemorrhage (SAH), we examined the effect of ozagrel, a thromboxane A2 (TXA2) synthetase inhibitor, on chronic vasospasm in a canine two-hemorrhage model in comparison with that of fasudil, an inhibitor of protein kinases. The magnitude of the vasospasm was determined angiographically. On SAH day 7, a vasospasm was observed in every dog. Intraarterial or intravenous administration of ozagrel (3 mg/kg/30 min) did not reverse the vasospasm but tended to increase bleeding. In contrast, intraarterial administration of fasudil (3 mg/kg/30 min) significantly reversed the vasospasm. These findings suggest that: 1) TXA2 does not participate in the maintenance of chronic vasospasm after SAH; and 2) the protein kinases, particularly myosin-light chain kinase and protein kinase C, are involved in the pathogenesis of arterial narrowing during the chronic phase of cerebral vasospasm.