Summary
The prevention of cerebral vasospasm with OKY-046, an imidazole derivative and a thromboxane synthetase inhibitor, was studied co-operatively at ten neurosurgical services. Intravenous administrations of 2, 5 or 10 μ/kg/minute of OKY-046 were given continuously from the earliest possible day to the 14th SAH-day to 82 pateints with ruptured cerebral aneurysm. Sixty-eight patients (83%) showed moderate to high high-density (SAH) in their initial CTs. Angiographic vasospasms were seen in 58 patients, representing 71% of all cases or 81% of the 72 cases for which angiograms were available; the vasospasms of 45 patients (55 or 63%) were moderate to severe. Symptomatic vasospasm occurred, however, only in 27 patients (33%); in 18 of those cases, moreover, the symptoms were mild or transient. The conditions of the patients at one month after the SAH were classified into 9 grades from 0 (normal) to 8 (deceased). Fifty-two patients (63%) were classified as 0 or 1, and 64 (78%) as better than 3 (possible daily life unaided). The administration of OKY-046 was proven to decrease TXB2 in the blood.
This paper emphasizes the effectiveness of the drug for symptomatic vasospasm, and supports our previous contention that cerebral microthrombosis may play an important role in the pathogenesis of cerebral vasospasm.
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Allen, G. S., Ahn, H. S., Preziosi, T. J., Battye, R., Boone, S. C., Chou, S. N., Kelly, D. L., Weir, B. K., Crabbe, R. A., Lavik, P. J., Rosenbloom, S. B., Dorsey, F. C., Ingram, C. R., Mellits, D. E., Bertsh, L. A., Boisvert, D. J. P., Hundley, M. B., Johnson, R. K., Strom, J. A., Transou, C. R., Cerebral arterial spasm—A controlled trial of nimodipine in patients with subarachnoid hemorrhage. New Eng. J. Med.308 (1983), 619–624.
Allen, G. S., Henderson, L. M., Chou, S. N., French, L. A., Cerebral arterial spam. Part 1: In vitro contractile activity of vasoactive agents in canine basilar and middle cerebral arteries. J. Neurosurg.40 (1974), 433–441.
Asano, T., Sasaki, T., Ochiai, C., Takakura, K., In vitro evaluation of the inhibitory action of PGI2 to vasoconstrictions induced by various prostaglandins, serotonin and hemoglobin using the canine basilar artery. Neurol. Med. Chir. (Tokyo)22 (1982), 507–512.
Boullin, D. J., Bunting, S., Blaso, W. P., Hunt, T. M., Moncada, S., Responses of human and baboon arteries to prostaglandin endoperoxides and biologically generated and synthetic prostacyclin: Their relevance to cerebral arterial spasm in man. Br. J. Clin. Pharmac.7(1979), 139–147.
Chapleau, C. E., White, R. P., Robertson, J. T., Cerebral vasodilation and prostacyclin. The effects of aspirin and meclofenamate in vitro. J. Neurosurg.53 (1980), 188–192.
Doi, A., Kishikawa, H., Takemoto, M., Baba, Y., Eguchi, T., Yoshioka, J., Takasugi, N., Ohmoto, T., Yabuno, N., Prevention of cerebral ischemia with vasospasm—Prophylactic use of thromboxane A2 inhibitor. Proceedings of the 11th Conference of Surgical Treatment of Stroke (Japan). Tokyo, Neuron Co., 1982, pp. 151–154.
Ellis, E. F., Nies, A. S., Oates, J. A., Cerebral arterial smooth muscle contraction by thromboxane A2. Stroke8 (1977), 480–483.
Fukumori, T., Tani, E., Maeda, Y., Sukenaga, A., Effect of selective inhibitor of thromboxane A2 synthetase on experimental cerebral vasospasm. Stroke15 (1984), 303–311.
Kaneko, M., Hosoda, Y., Koga, H., Experience of per-acute operation for severe type of ruptured intracranial aneurysm—application of repeated irrigation of basal cistern. Neurol. Med. Chir. (Tokyo)20 (1980), 915–921.
Kapp, J. P., Robertson, J. T., White, R. P., Spasmogenic qualities of prostaglandin F2α in the cat. J. Neurosurg.44 (1976), 173–175.
LaTorre, E., Patrono, C., Fortuna, A., Grossi-Belloni, D., Role of prostaglandin F2 in human cerebral vasospasm. J. Neurosurg.41 (1974), 293–299.
Maeda, Y., Tani, E., Miyamoto, T., Prostaglandin metabolism in experimental cerebral vasospasm. J. Neurosurg.55 (1981), 779–785.
Mizukami, K., Kitamura, K., Kikuchi, H., Ono, H., Ogawa, N., Preventive effect of antiplatelet agent Ticlopidine on cerebral ischemia due to vasospasm following ruptured aneurysm: A double-blind co-operative study. Surg. Diag. Treat. (Japan)25 (1983), 117–130.
Naito, J., Hiraku, S., Kuga, T., Thromboxane A2 (TXA2) synthetase inhibition by (E)-3-[4-(imidazolymethyl)phenyl]-2-propenoic acid hydrochloride monohydrate (OKY-046) and sodium (E)-3-[4(3-pyridylmethyl)phenyl]-2-methyl-propenoate (OKY-1581), and their medical usefulness. Pharmacometrics (Japan)27 (1984), 267–287.
Ochiai, C., Asano, T., Takakura, K., Tamura, A., Sano, K., Kubota, M., Mizutani, H., Basugi, N., Yoshimasu, N., Saito, I., A double-blind evaluation of the effect of Nizofenone (Y-9179) on delayed ischemic deficits following SAH. Proceedings of the 11th Conference of Surgical Treatment of Stroke (Japan). Tokyo, Neuron Co., 1982, pp. 324–330.
Ohmoto, T., Morooka, H., Shibata, K., Nishimoto, A., Noradrenergic mechanism of experimental cerebral vasospasm. Neurol. Med. Chir. (Tokyo)16 (1976), 525–534.
Ohta, T., Waga, S., Handa, H., Saito, I., Takeuchi, K., Suzuki, J., Takaku, A., New grading of level of disordered consciousness. Neurol. Surg. (Tokyo)2 (1974), 623–627.
Quintana, L., Konda, R., Ishibashi, Y., Yoshimoto, T., Suzuki, J., The effect of prostacyclin on cerebral vasospasm. An experimental study. Acta Neurochir. (Wien)62 (1982), 182–193.
Sasaki, T., Murota, S., Wakai, S., Asano, T., Sano, K., Evaluation of prostaglandin biosynthetic activity in canine basilar artery following subarachnoid injection of blood. J. Neurosurg.55 (1981), 771–778.
Sasaki, T., Wakai, S., Asano, T., Takakura, K., Sano, K., Prevention of cerebral vasospasm after SAH with a thromboxane synthetase inhibitor, OKY-1581. J. Neurosurg.57 (1982), 74–82.
Suzuki, S., Sobata, E., Ando, A., Iwabuchi, T., Anaerobic changes of bloody CSF in subarachnoid haemorrhage: Its relation to cerebral vasospasm. Acta Neurochir. (Wien)58 (1981), 15–26.
Suzuki, S., Sobata, E., Iwabuchi, T., Prevention of cerebral ischemic symptoms in cerebral vasospasm with trapidil, an antagonist and selective synthesis inhibitor of thromboxane A2. Neurosurgery9 (1981), 679–685.
Suzuki S., Suzuki, M., Iwabuchi, T., Kamata, Y., Role of multiple cerebral microthrombosis in symptomatic cerebral vasospasm: With a case report. Neurosurgery13 (1983), 199–203.
Suzuki, S., White, R. P., Chapleau, C. E., Robertson, J. T., An experimental evaluation of anaerobic condition in the pathogenesis of cerebral vasospasm associated with subarchnoid hemorrhage. A preliminary report. Hirosaki Med. J.32 (1980), 48–56.
Tani, E., Maeda, Y., Fukumori, T., Nakano, M., Kochi, N., Morimura, T., Yokota, M., Matsumoto, T., Effect of selective inhibitor of thromboxane A2 synthetase on cerebral vasospasm after early surgery. J. Neurosurg.61 (1984), 24–29.
Walker, V., Pickard, J. D., Smythe, P., Eastwood, S., Perry, S., Effects of subarachnoid haemorrhage on intracranial prostaglandins. J. Neurol. Neurosurg. Psychiat.46 (1983), 119–125.
Yabuno, N., Motoki, M., Yoshino, K., Yoshioka, J., Ohmoto, T., Nishimoto, A., Doi, A., Effects of PGI2 and TXA2 synthetase inhibitor (OKY-1581) on experimental vasospasm. Proceedings of the 11th Conference of Surgical Treatment of Stroke (Japan). Tokyo, Neuron. Co., 1982, pp. 133–138.
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Suzuki, S., Iwabuchi, T., Tanaka, T. et al. Prevention of cerebral vasospasm with OKY-046 an imidazole derivative and a thromboxane synthetase inhibitor. A preliminary co-operative clinical study. Acta neurochir 77, 133–141 (1985). https://doi.org/10.1007/BF01476216
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DOI: https://doi.org/10.1007/BF01476216