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Effect of High-Dose Simvastatin on Cerebral Blood Flow and Static Autoregulation in Subarachnoid Hemorrhage

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Abstract

Background

Statins may promote vasodilation following subarachnoid hemorrhage (SAH) and improve the response to blood pressure elevation. We sought to determine whether simvastatin increases cerebral blood flow (CBF) and alters the response to induced hypertension after SAH.

Methods

Statin-naïve patients admitted <72 h after WFNS ≥2 aneurysmal SAH were randomly assigned to 80 mg simvastatin/day or placebo for 21 days. Regional CBF was measured with quantitative 15O PET on SAH day 7–10 before and after raising mean arterial pressure (MAP) 20–25 %. Autoregulatory index (AI) was calculated as the ratio of % change in resistance (MAP/CBF) to % change in MAP. Angiography was performed within 24 h of PET. Results are presented as simvastatin vs. placebo.

Results

Thirteen patients received simvastatin and 12 placebo. Clinical characteristics were similar. Moderate or severe angiographic vasospasm occurred in 42 vs. 45 % and delayed cerebral ischemia in 14 vs. 55 % (p = 0.074). During PET studies, MAP (110 ± 10 vs. 111 ± 12), global CBF (41 ± 12 vs. 43 ± 13), and CVR (2.95 ± 1.0 vs. 2.81 ± 1.0) did not differ at baseline. When MAP was raised to 135 ± 7 mm Hg vs. 137 ± 15, global CBF did not change. Global AI did not differ (107 ± 59 vs. 0. 89 ± 52 %, p = 0.68). CBF did not change in regions with low baseline flow or in regions supplied by vessels with angiographic vasospasm in either group. Six-month modified Rankin Scale scores did not differ.

Conclusions

Our data indicate that initiation of therapy with high-dose simvastatin does not alter baseline CBF or response to induced hypertension.

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Acknowledgments

This research was supported by NIH/NINDS: P50 NS055977.

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Authors and Affiliations

  1. Department of Neurology, Washington University, Campus Box 8111, 660 S Euclid Ave, St Louis, MO, 63110, USA

    Michael N. Diringer, Rajat Dhar, Allyson R. Zazulia & Colin P. Derdeyn

  2. Department of Neurological Surgery, Washington University, St. Louis, MO, USA

    Michael N. Diringer, Michael Chicoine & Colin P. Derdeyn

  3. Department of Radiology, Washington University, St. Louis, MO, USA

    Allyson R. Zazulia & Colin P. Derdeyn

  4. Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    William J. Powers

  5. Kansas City University of Medicine and Biosciences, Kansas City, MO, USA

    Michael Scalfani

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  1. Michael N. Diringer
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  2. Rajat Dhar
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  3. Michael Scalfani
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  5. Michael Chicoine
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Correspondence to Michael N. Diringer.

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Diringer, M.N., Dhar, R., Scalfani, M. et al. Effect of High-Dose Simvastatin on Cerebral Blood Flow and Static Autoregulation in Subarachnoid Hemorrhage. Neurocrit Care 25, 56–63 (2016). https://doi.org/10.1007/s12028-015-0233-7

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  • DOI: https://doi.org/10.1007/s12028-015-0233-7

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