Cerebrovascular and metabolic changes during the delayed vasospasm following experimental subarachnoid hemorrhage in baboons, and treatment with a calcium antagonist.
A model has been designed in baboons for simulating the clinical situation during the late phase of vasospasm in patients with subarachnoid hemorrhage (SAH). A total amount of 14-33 ml autologous blood was injected into the cisternal system on 3 occasions in the course of 4 days. Neurological symptoms were seen, and the mortality rate was 29%. Angiography 3 days after the last injection showed arterial vasoconstriction amounting to 23% in the vertebro-basilar system, and 11% (right) and 18% (left) in the carotid system. Cerebral blood flow (CBF) measured by the intra-arterial 133Xe technique and the cerebral metabolic rate of oxygen (CMRO2) were reduced by 18% and 11%, respectively. The hypercapnic CBF response was significantly impaired, from a mean of 3.90 ml/100 g/min to 1.72 ml/100 g/min of flow increase for each mm Hg elevation of paCO2. Autoregulation, tested by administration of angiotensin II, was also significantly affected as evidenced by a pressure-dependent increment of CBF during hypertension in 5 out of 7 animals tested. The impaired autoregulation was reflected in the autoregulatory index, which in the whole group increased from 0.06 ml/100 g/min for each mm Hg increase in MABP in the pre-SAH animals to 0.29 ml/100 g/min per mm Hg post-SAH. Treatment with the calcium antagonist, nimodipine (0.5 microgram/kg/min i.v. during 45 min), enhanced CBF significantly by 17% before experimental SAH, whereas after SAH the effect was slight and did not reach statistical significance; CMRO2 was not significantly affected in either group. Intravenous nimodipine combined with hypertension resulted in a marked increase in the autoregulatory index to 1.58 ml/100 g/min per mm Hg in pre-SAH animals and a less pronounced increment to 0.58 ml/100 g/min per mm Hg following experimental SAH. The beneficial effect of nimodipine reported in SAH patients is therefore, in view of our findings, more likely due primarily to a protective mechanism at the cellular level than to an influence on the vascular bed.
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D002533:Cerebral Angiography; D002536:Cerebral Arteries / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal / Q000378:metabolism / Q000401:mortality; D005260:Female; D006935:Hypercapnia / Q000097:blood / Q000378:metabolism; D006973:Hypertension / Q000097:blood; D008297:Male; D009553:Nimodipine / Q000627:therapeutic use*; D010101:Oxygen Consumption; D010215:Papio; D013035:Spasm; D013345:Subarachnoid Hemorrhage / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*
D009553:Nimodipine