Introduction: Numerous studies show that transient exposure to mild ischemia renders the brain resistant to a subsequent more severe ischemic stimulus, a concept known as preconditioning. Excitingly, this phenomenon has recently been demonstrated in subarachnoid hemorrhage (SAH), as mice transiently exposed to hypoxia developed an eNOS-mediated reduction vasospasm and neurological deficits following experimental SAH; however, this has never been studied in humans. In the present study, we hypothesize that patients with pre-existent steno-occlusive vascular disease experience ischemic preconditioning resulting in reduced SAH-induced cerebral vasospasm.

Methods: Retrospective case-controlled data from five high-volume SAH centers from 2006-2011 were pooled. Only Fisher 3-4 patients were included. The effect of pre-existent steno-occlusive vascular disease (extra- and intra-cranial atherosclerotic disease, and peripheral vascular disease) on the following endpoints was studied: angiographic vasospasm, symptomatic vasospasm, and stroke. Multivariate logistic regression analysis was performed with the following covariables; age, gender, Hunt-Hess grade, neurological deficit on admission, aneurysm location and type of aneurysm treatment.

Results: A total of 771 patients were included, of which 198 (25.7%) had pre-existent vascular disease, 573 (74.3%) did not. Of those patients that had pre-existent vascular disease, 49 (24.7%) developed radiographic vasospasm, 30 (15.2%) symptomatic vasospasm and 26 delayed stroke (13.1%). Of those patients that did not have pre-existent vascular disease, 245 (42.8%) developed radiographic vasospasm, 131 (22.9%) symptomatic vasospasm, 84 (14.7%) delayed stroke. Multivariate logistic regression analysis demonstrated that older age and pre-existent vascular disease were significantly related with protection from radiographic and symptomatic vasospasm. Patients with pre-existent vascular disease had lower incidence of radiographic vasospasm (odds ratio, 0.524; 95% CI, 0.361-.0761; P=.001) and symptomatic vasospasm (odds ratio, 0.584; 95% CI, 0.385-0.885, P=0.011).

Conclusions: These retrospective case-controlled data are the first evidence in human patients that ischemic preconditioning has an effect on reducing the incidence of angiographic and symptomatic vasospasm in patients with aneurysmal SAH.

Patient Care: Aggressive use of preventive therapies for vasospasm, such as ‘‘triple-H’’ therapy may be associated with neurolologic and medical complications, such as worsening cerebral edema and hemorrhagic infarction, pulmonary edema, dilutional hyponatremia, and myocardial infarction. Our findings confirmed that patients with pre-existent vascular disease had lower incidence of radiographic and symptomatic vasospasm. Therefore, this evidence has to be taken into consideration when performing aggressive preventive therapies for vasospasm.

Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the predictors of cerebral vasospasm after SAH. 2) Describe the importance of an ischemic preconditioning effect on cerebral vasospasm in patients with SAH.

References: 1. Keep RF, Wang MM, Xiang J, Hua Y, Xi G. Is there a place for cerebral preconditioning in the clinic? Translational stroke research. 2010;1:4-18 2. Kharbanda RK, Nielsen TT, Redington AN. Translation of remote ischaemic preconditioning into clinical practice. Lancet. 2009;374:1557-1565 3. Dirnagl U, Becker K, Meisel A. Preconditioning and tolerance against cerebral ischaemia: From experimental strategies to clinical use. Lancet Neurol. 2009;8:398-412 4. Ryttlefors M, Enblad P, Ronne-Engstrom E, Persson L, Ilodigwe D, Macdonald RL. Patient age and vasospasm after subarachnoid hemorrhage. Neurosurgery 2010;67:911-917