Vasospasm in Monkeys Resolves Because of Loss of and Encasement of Subarachnoid Blood Clot

Abstract

Background and Purpose-We studied in monkeys why vasospasm resolves after subarachnoid hemorrhage (SAH). Methods-Monkeys underwent angiography and right (nϭ17) or bilateral (nϭ8) SAH. Animals with bilateral SAH underwent angiography 1, 3, 5, and 7 days later. Animals with right SAH underwent angiography 7 days later. The clot was then not removed (nϭ5), removed and replaced with fresh clot (nϭ7), or removed and not replaced (nϭ5). At the same time on day 7, the removed clot (nϭ12) or fresh clot (nϭ5) was placed on the left side. Angiography was repeated every 2 days until day 14. Results-SAH caused significant vasospasm on day 7 that resolved by day 14. Removal of clot on day 7 resulted in more rapid resolution of vasospasm. Placement of fresh clot onto arteries that had already been exposed to clot for 7 days produced vasospasm that persisted without resolving for an additional 7 days. Placement of 7-day-old clot from the right onto previously unexposed left arteries or of clot from blood removed from an animal 7 days after SAH caused significantly more rapid onset of vasospasm compared with de novo vasospasm. Microscopic examination of the clots showed they were surrounded by macrophages 7 days after SAH. Arterial compliance and contractility were reduced in relation to duration of the exposure of arteries to clot. Conclusions-Vasospasm resolves because of loss of subarachnoid blood clot. We hypothesize that reduced spasmogen release from the clot contributes to resolution of vasospasm. There was no response in the cerebral arteries that rendered them less responsive to the subarachnoid clot.

Standard intracranialin vivoanimal models of delayed cerebral vasospasm

“…Eleven angiographic studies addressed the time course of sham-operated monkeys with craniotomy and blood clot placement without any further manipulations. 128,133,136,137,[139][140][141][142][143][144][145] . These studies measured either reduction of the middle cerebral artery 136,137,139,[142][143][144][145] or combined reduction 128,133,140,141 of the internal carotid artery, middle cerebral artery, and anterior cerebral artery compared to the baseline angiographic vessel diameter.…”

“…125,128,133,[140][141][142][143][144][145] Three studies measured marked vasospasm beginning on day 3 and persisting through day 7. 136,137,139 Cat, pig, and goat. A large variety of SAH techniques were proposed in cats.…”

Current Perspective on the Role of the Thrombin Receptor in Cerebral Vasospasm After Subarachnoid Hemorrhage

“…However, the amount of blood in the subarachnoid space has been shown to correlate with the severity of vasospasm in SAH patients and animal models (5,6), while the removal of blood clots reverses angiographic vasospasm in animal models (7,8). As a result, it is conceivable that the presence of blood or the breakdown products of blood are responsible, either directly or indirectly, for the develop-ment of cerebral vasospasm (9,10).…”

Does Prevention of Vasospasm in Subarachnoid Hemorrhage Improve Clinical Outcome? No

“…[12][13][14][15] These studies isolated a single pathogenic factor, namely the hematoma encasing proximal vessels, as the cause of delayed vasospasm. Delayed vasospasm per itself in this model was insufficient for causing severe delayed neurological deficit.…”