✓ To evaluate the pathogenetic role of alterations in the physical properties of the arterial wall (the passive component) and of active smooth-muscle contraction (the active component) in the occurrence of chronic vasospasm, the temporal profiles of these events were examined using the canine “two-hemorrhage” model. In the in vivo study, the basilar artery was exposed via the transclival approach on Day 0, 2, 4, 7, or 14. Nicardipine, followed by the protein kinase C inhibitor H-7, then papaverine were administered in a cumulative fashion, and the change in the basilar artery diameter induced by the addition of each agent was recorded angiographically. Drug administration markedly reversed the arterial narrowing caused by chronic vasospasm. When the vasodilatory effect of each agent was compared, the dilation induced by nicardipine or papaverine progressively decreased from Day 2 to Day 7, whereas that induced by H-7 increased. The in vitro experiment using arterial segments excised from the basilar artery revealed a progressive increase in arterial stiffness from Day 2 to Day 7. Also, there was a significant decrease in the initial half-circumference of the arterial segment, which was at its maximum on Days 4 and 7. However, the alteration in the initial half-circumference was considerably less than that in the angiographic diameter following subarachnoid hemorrhage. These data indicate that the augmented spontaneous tonus of the smooth muscle plays the predominant role in the occurrence of chronic vasospasm. Thus, the involvement of the protein kinase C-mediated contractile system is strongly suggested.
Toru Matsui, Hiroyuki Kaizu, Shoichi Iron and Takao Asano
Lipid peroxidation as a possible cause of postischemic injury
Shinichi Yoshida, Satoshi Inoh, Takao Asano, Keiji Sano, Masaru Kubota, Hiroyuki Shimazaki and Nobuo Ueta
✓ The effect of transient bilateral carotid occlusion on levels of free fatty acids, phospholipids, and lipid peroxides in the brain was studied in gerbils. During occlusion, both saturated and polyunsaturated free fatty acids increased strikingly to approximately 11-fold in total by 30 minutes. During recirculation, however, a selectively rapid decrement occurred in arachidonic acid, while saturated fatty acids gradually decreased to their basal levels in 180 minutes. The peroxide level, estimated by a thiobarbituric acid test, did not change during occlusion, but was elevated on reperfusion. Phosphatidylethanolamine content decreased throughout the periods examined. These results do not support a hypothesis that lipid peroxidation is initiated during ischemia by the lack of oxygen at the terminus of the mitochondrial respiratory chain. Instead, it is suggested that severe cerebral ischemia disintegrates membrane phospholipids, probably through activation of hydrolytic enzymes, and that overt peroxidative processes take place during reflow by means of restoration of oxygen supply. The peroxidative reactions may, indeed, cause additional damage during the postischemic phase.