The role of active smooth-muscle contraction in the occurrence of chronic vasospasm in the canine two-hemorrhage model

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✓ 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.

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Address reprint requests to: Toru Matsui, M.D., Department of Neurosurgery, Saitama Medical Center, 1981, Kamoda, Kawagoe, Saitama 350, Japan.

© AANS, except where prohibited by US copyright law.

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Figures

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    Drawing illustrating the chamber system. The basilar artery segment is mounted on triangular rigid prongs in aerated Krebs-Henseleit solution. The upper and lower prongs are fixed to straight stainless-steel wires connected to a transducer (A) and an unshakable platform. The initial arterial half-circumference is representative of the length (L) between the stainless-steel wires of the two prongs, by which the artery segment is stretched in increments of 0.2 mm.

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    Bar graph showing the time course of vascular tone after the cumulative administration of nicardipine, H-7, and papaverine in transclivally exposed basilar artery subjected to experimental subarachnoid hemorrhage. The increase in the angiographic diameter developed at each step in the cumulative addition (“Accumulation-1, 2, and 3”) is shown as a percentage of the total increase in angiographic diameter by the three pharmacological agents. The vascular active tone significantly decreased as chronic vasospasm developed. However, the response to H-7 increased remarkably on Days 4 and 7. These events returned to normal on Day 14. Statistical significance: * = p < 0.05; ** = p < 0.01, compared to control and Day 14.

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    Bar graph showing the initial arterial half-circumference, defined as the circumference at which a minimal tension developed after stretching the basilar artery, measured on Day (D) 0, 2, 4, 7, and 14 after induction of sub-arachnoid hemorrhage. Statistical significance: * = p < 0.01, compared to Days 0 and 14.

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    Graph demonstrating the time course of the tension-length curves of basilar arteries subjected to experimental sub-arachnoid hemorrhage. As chronic vasospasm developed, the stiffness of the basilar artery increased but then tended to be reversed to the control level on Day 14.

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    Bar graph showing basilar artery compliance (distensibility) based on the tension-length curve. A remarkable reduction in the basilar arterial distensibility was demonstrated at the stretching increments from 0.0 to 0.2 mm and from 0.2 to 0.4 mm on Days 4 and 7 after subarachnoid hemorrhage (SAH), then returned to normal on Day 14. Statistical significance: * = p < 0.05, compared to control.

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