Pharmacologic irreversible narrowing in chronic cerebrovasospasm in rabbits is associated with functional damage.

Abstract

We studied isolated basilar artery segments from a rabbit model of chronic cerebrovasospasm. Autologous blood placed around the basilar artery of rabbits killed 1, 2, 3, 4, 5, 6, 7, or 9 days later caused narrowing of the segments with a biphasic time course. The first (immediate) phase was reversed by intra-arterial papaverine; the second phase exhibited an increasing component of narrowing that was papaverine-insensitive. Based on the passive force/length curves, basilar artery segments became increasingly stiff over 9 days. By contrast, the segments' contractility decreased. Responses of the basilar artery segments were greater over the first few days, but then became less than that of saline-injected controls. Contractions in response to norepinephrine and potassium were reduced. Endothelium-based acetylcholine-induced vasodilation progressively diminished, as did the response to sympathetic nerve stimulation. There was a negative correlation between artery wall stiffness and contractility. The papaverineinsensitive component of angiographic narrowing correlated directly with loss of contractility and with artery wall stiffness. These results are consistent with the conclusion that increased artery wall stiffness is a primary determining factor in the arterial narrowing of chronic cerebrovasospasm. {Stroke 1990;21:1478-1484) R efractoriness of chronic cerebrovasospasm to pharmacologic vasodilator therapy has been widely reported in humans and in some animal models. 23 This feature probably reflects the primary basis of the clinical concern with cerebrovasospasm. In humans the first clinical evidence of this state is seen 3-4 days after subarachnoid hemorrhage (SAH); cerebrovasospasm reaches its maximum after approximately 7 days and reverses after several weeks. 45 We have recently developed a model of SAH in rabbits. Papaverine-sensitive and -insensitive narrowing of the basilar artery was determined by serial angiography over 9 days after the placement of 3 ml/kg autologous blood by multiple injections around the base of the brain. 6 The papaverine-insensitive component began 3-5 days after blood placement and subsequently progressed slowly, representing 63% of the total narrowing at day 9.

Quantitative Analysis of Gene Expressions Related to Inflammation in Canine Spastic Artery After Subarachnoid Hemorrhage

“…Increased synthesis of collagen type I may be related to increased artery wall stiffness, which may contribute to the sustained arterial narrowing of cerebral vasospasm. 20 The expression of the collagen type I gene was upregulated by cytokines such as IL-1, interferon-␥, TNF-␣, and TNF-␤ and growth factors such as platelet-derived growth factor, TGF-␤, in human vascular smooth muscle cells. 17 We previously reported that TGF-␤ gene expression in rat femoral artery is stimulated after exposure to blood.…”

Technical considerations on intra-arterial papaverine hydrochloride for cerebral vasospasm

“…Vorkapic et al [30] successfully produced vasospasm after SAH in the rabbit. In this situation, intra-arterial papaverine was effective in reversing angiographic vasospasm in the first 3 days following its appearance.…”

Clentiazem protects against chronic cerebral vasospasm in rabbit basilar artery.

“…This was compared with measurements in shamoperated animals. 23 At day 2, no differences were detected (Figure 2). In the untreated group on day 5, the passive wall force was 213 ±22% of control, and this increased to 274±30% on day 9, which was indicative of increased vessel wall stiffness.…”

“…23 Since loss of contractility can also be correlated with irreversible narrowing, excessive active muscle tone does not make a sizeable contribution to narrowing. The arterial narrowing observed in the clentiazem-treated group was reversed by papaverine.…”