Preconditioning effect on cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage.

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.

[1]  J. Provencio,et al.  Low-dose lipopolysaccharide injection prior to subarachnoid hemorrhage modulates Delayed Deterioration associated with vasospasm in subarachnoid hemorrhage. , 2013, Acta neurochirurgica. Supplement.

[2]  J. Gidday,et al.  Junctional Protein Regulation by Sphingosine Kinase 2 Contributes to Blood–Brain Barrier Protection in Hypoxic Preconditioning-Induced Cerebral Ischemic Tolerance , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[3]  R. Ostrowski,et al.  CHOP Silencing Reduces Acute Brain Injury in the Rat Model of Subarachnoid Hemorrhage , 2012, Stroke.

[4]  J. Pepper,et al.  Effect of remote ischemic preconditioning on clinical outcomes in patients undergoing coronary artery bypass graft surgery (ERICCA): rationale and study design of a multi-centre randomized double-blinded controlled clinical trial , 2012, Clinical Research in Cardiology.

[5]  John H. Zhang,et al.  Apoptotic mechanisms for neuronal cells in early brain injury after subarachnoid hemorrhage. , 2011, Acta neurochirurgica. Supplement.

[6]  C. Iadecola,et al.  Stroke research at a crossroad: asking the brain for directions , 2011, Nature Neuroscience.

[7]  C. Hahn,et al.  Remote Ischemic Per-Conditioning: A Novel Therapy for Acute Stroke? , 2011, Stroke.

[8]  U. Dirnagl,et al.  Protective conditioning of the brain: expressway or roadblock? , 2011, The Journal of physiology.

[9]  A. Redington,et al.  Potent neuroprotection induced by remote preconditioning in a rat model of neonatal cerebral hypoxic-ischemic injury. , 2011, The Journal of thoracic and cardiovascular surgery.

[10]  A. Stowe,et al.  Repetitive hypoxia extends endogenous neurovascular protection for stroke , 2011, Annals of neurology.

[11]  M. Perez-Pinzon,et al.  Remote Ischemic Limb Preconditioning After Subarachnoid Hemorrhage: A Phase Ib Study of Safety and Feasibility , 2011, Stroke.

[12]  Tej D. Azad,et al.  Endothelial Nitric Oxide Synthase Mediates Endogenous Protection Against Subarachnoid Hemorrhage-Induced Cerebral Vasospasm , 2011, Stroke.

[13]  V. Tsang,et al.  Remote Ischemic Preconditioning Protects the Brain Against Injury After Hypothermic Circulatory Arrest , 2011, Circulation.

[14]  Gang Chen,et al.  Influence of simvastatin on microthrombosis in the brain after subarachnoid hemorrhage in rats: a preliminary study. , 2010, Annals of clinical and laboratory science.

[15]  R. Macdonald,et al.  Patient Age and Vasospasm After Subarachnoid Hemorrhage , 2010, Neurosurgery.

[16]  R. Carpenter,et al.  Remote Ischemic Preconditioning for Cerebral and Cardiac Protection During Carotid Endarterectomy: Results From a Pilot Randomized Clinical Trial , 2010, Vascular and endovascular surgery.

[17]  J. Gidday,et al.  Hypoxic Preconditioning-Induced Cerebral Ischemic Tolerance: Role of Microvascular Sphingosine Kinase 2 , 2009, Stroke.

[18]  U. Dirnagl,et al.  Preconditioning and tolerance against cerebral ischaemia: from experimental strategies to clinical use , 2009, The Lancet Neurology.

[19]  P. Faries,et al.  Ischemic Preconditioning during the Use of the Percusurge Occlusion Balloon for Carotid Angioplasty and Stenting , 2008, Vascular.

[20]  John H. Zhang,et al.  Oxidative stress in subarachnoid haemorrhage: significance in acute brain injury and vasospasm. , 2008, Acta neurochirurgica. Supplement.

[21]  J. Gidday,et al.  Oxygen Sensing : Life and Death of a Cell Hypoxic preconditioning protects human brain endothelium from ischemic apoptosis by Akt-dependent survivin activation , 2007 .

[22]  T. Nowak,et al.  CBF Changes Associated with Focal Ischemic Preconditioning in the Spontaneously Hypertensive Rat , 2006, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[23]  J. Gidday Cerebral preconditioning and ischaemic tolerance , 2006, Nature Reviews Neuroscience.

[24]  H. Steiger,et al.  Ischaemic preconditioning of the brain, mechanisms and applications , 2006, Acta Neurochirurgica.

[25]  D. Busija,et al.  Diazoxide preconditioning attenuates global cerebral ischemia-induced blood–brain barrier permeability , 2005, Brain Research.

[26]  U. Dirnagl,et al.  Neuroprotective role of astrocytes in cerebral ischemia: Focus on ischemic preconditioning , 2005, Glia.

[27]  W. Poon,et al.  Effect of ischemic preconditioning on brain tissue gases and pH during temporary cerebral artery occlusion. , 2005, Acta neurochirurgica. Supplement.

[28]  T. Neumann-Haefelin,et al.  Transient ischaemic attack preceding anterior circulation infarction is independently associated with favourable outcome. , 2004, Journal of neurology, neurosurgery, and psychiatry.

[29]  A. Villringer,et al.  Transient Ischemic Attacks Before Ischemic Stroke: Preconditioning the Human Brain?: A Multicenter Magnetic Resonance Imaging Study , 2004, Stroke.

[30]  S. Mayer,et al.  Cerebral vasospasm after subarachnoid hemorrhage , 2003, Current opinion in critical care.

[31]  R. Bordet,et al.  Delayed Cerebrovascular Protective Effect of Lipopolysaccharide in Parallel to Brain Ischemic Tolerance , 2003, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[32]  R. Keep,et al.  Attenuation of Ischemic Brain EDEMA and Cerebrovascular Injury after Ischemic Preconditioning in the Rat , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[33]  J. Hallenbeck,et al.  Cerebrovascular Hemodynamics and Ischemic Tolerance: Lipopolysaccharide-Induced Resistance to Focal Cerebral Ischemia is not Due to Changes in Severity of the Initial Ischemic Insult, but is Associated with Preservation of Microvascular Perfusion , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[34]  A. Algra,et al.  Case-fatality rates and functional outcome after subarachnoid hemorrhage: a systematic review. , 1997, Stroke.

[35]  T. Inagawa Cerebral vasospasm in elderly patients with ruptured intracranial aneurysms. , 1991, Surgical neurology.

[36]  R. Jennings,et al.  Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. , 1986, Circulation.

[37]  J. Bogousslavsky,et al.  [Transient ischemic attacks before and after occlusion of the internal carotid artery]. , 1983, Revue neurologique.