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Preconditioning Effect on Cerebral Vasospasm in Patients With Aneurysmal Subarachnoid Hemorrhage

Kim, Young Woo MD*; Zipfel, Gregory J. MD; Ogilvy, Christopher S. MD§; Pricola, Katie L. MD§; Welch, Babu G. MD; Shakir, Nabeel BS; Patel, Bhuvic BS; Reavey-Cantwell, John F. MD; Kelman, Craig R. MD; Albuquerque, Felipe C. MD#; Kalani, M. Yashar S. MD, PhD#; Hoh, Brian L. MD**

doi: 10.1227/NEU.0000000000000282
Research-Human-Clinical Studies

BACKGROUND: Recent experimental evidence indicates that endogenous mechanisms against cerebral vasospasm can be induced via preconditioning.

OBJECTIVE: To determine whether these vascular protective mechanisms are also present in vivo in humans with aneurysmal subarachnoid hemorrhage.

METHODS: A multicenter retrospective cohort of patients with aneurysmal subarachnoid hemorrhage was examined for ischemic preconditioning stimulus: preexisting steno-occlusive cerebrovascular disease (CVD) and/or previous cerebral infarct. Generalized estimating equation models were performed to determine the effect of the preconditioning stimulus on the primary end points of radiographic vasospasm, symptomatic vasospasm, and vasospasm-related delayed cerebral infarction and the secondary end point of discharge modified Rankin Scale score.

RESULTS: Of 1043 patients, 321 (31%) had preexisting CVD and 437 (42%) had radiographic vasospasm. Patients with preexisting CVD were less likely to develop radiographic vasospasm (odds ratio = 0.67; 95% confidence interval = 0.489-0.930; P = .02) but had no differences in other end points. In terms of the secondary end point, patients with preexisting CVD did not differ significantly from patients without preexisting CVD in mortality or unfavorable outcome in multivariate analyses, although patients with preexisting CVD were marginally more likely to die (P = .06).

CONCLUSION: This retrospective case-control study suggests that endogenous protective mechanisms against cerebral vasospasm—a preconditioning effect—may exist in humans, although these results could be the effect of atherosclerosis or some combination of preconditioning and atherosclerosis. Additional studies investigating the potential of preconditioning in aneurysmal subarachnoid hemorrhage are warranted.

ABBREVIATIONS: aSAH, aneurysmal subarachnoid hemorrhage

CI, confidence interval

CVD, cerebrovascular disease

mRS, modified Rankin Scale

OR, odds ratio

VCI, vasospasm-related delayed cerebral infarction

*Department of Neurosurgery, Bucheon St. Mary's Hospital, Catholic University of Korea, Bucheon, Republic of Korea;

Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri;

§Neurovascular Service, Massachusetts General Hospital, Boston, Massachusetts;

Department of Radiology, UT Southwestern Medical Center, Dallas, Texas;

Department of Neurosurgery, Virginia Commonwealth University, Richmond, Virginia;

#Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona;

**Department of Neurosurgery, University of Florida, Gainesville, Florida

Correspondence: Brian L. Hoh, MD, Department of Neurosurgery, University of Florida, PO Box 100265, Gainesville, FL 32610. E-mail:

Received April 26, 2013

Accepted December 20, 2013

Copyright © by the Congress of Neurological Surgeons