Selim M. Perioperative stroke

Department of Neurology, Division of Cerebrovascular Diseases, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
New England Journal of Medicine (Impact Factor: 55.87). 03/2007; 356(7):706-13. DOI: 10.1056/NEJMra062668
Source: PubMed
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    • "In hypoxia and global brain ischemia models, short-term water-only fasting is protective [34]–[38]. However, while global brain hypoperfusion accounts for less than 10% of perioperative strokes in humans [2], the majority (62%) of perioperative strokes are caused by focal ischemic insults that are mechanistically and pathologically different from hypoperfusion. Our first objective was to assess the effect of short-term fasting on severe focal brain ischemia. "
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    ABSTRACT: Stroke is a major complication of cardiovascular surgery, resulting in over 100,000 deaths and over a million postoperative encephalopathies annually in the US and Europe. While mitigating damage from stroke after it occurs has proven elusive, opportunities to reduce the incidence and/or severity of stroke prior to surgery in at-risk individuals remain largely unexplored. We tested the potential of short-term preoperative dietary restriction to provide neuroprotection in rat models of focal stroke. Rats were preconditioned with either three days of water-only fasting or six days of a protein free diet prior to induction of transient middle cerebral artery occlusion using two different methods, resulting in either a severe focal stroke to forebrain and midbrain, or a mild focal stroke localized to cortex only. Infarct volume, functional recovery and molecular markers of damage and protection were assessed up to two weeks after reperfusion. Preoperative fasting for 3 days reduced infarct volume after severe focal stroke. Neuroprotection was associated with modulation of innate immunity, including elevation of circulating neutrophil chemoattractant C-X-C motif ligand 1 prior to ischemia and suppression of striatal pro-inflammatory markers including tumor necrosis factor α, its receptor and downstream effector intercellular adhesion molecule-1 after reperfusion. Similarly, preoperative dietary protein restriction for 6 days reduced ischemic injury and improved functional recovery in a milder cortical infarction model. Our results suggest that short-term dietary restriction regimens may provide simple and translatable approaches to reduce perioperative stroke severity in high-risk elective vascular surgery.
    PLoS ONE 04/2014; 9(4):e93911. DOI:10.1371/journal.pone.0093911 · 3.23 Impact Factor
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    • "Ischemic and hypoxic insults to the brain during surgery and anesthesia result in life-threatening complications including stroke. These complications occur at the rate of 0.08–0.7% in general surgery and 1.4–3.8% in cardiac surgery [1]. Pharmacologic interventions, including calcium channel blockers, free radical scavengers, and glutamate antagonists, have been introduced to prevent and/or ameliorate stroke [2]. "
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    ABSTRACT: Erythropoietin (EPO), originally identified as a hematopoietic growth factor produced in the kidney and fetal liver, is also endogenously expressed in the central nervous system (CNS). EPO in the CNS, mainly produced in astrocytes, is induced under hypoxic conditions in a hypoxia-inducible factor (HIF)-dependent manner and plays a dominant role in neuroprotection and neurogenesis. We investigated the effect of general anesthetics on EPO expression in the mouse brain and primary cultured astrocytes. BALB/c mice were exposed to 10% oxygen with isoflurane at various concentrations (0.10-1.0%). Expression of EPO mRNA in the brain was studied, and the effects of sevoflurane, halothane, nitrous oxide, pentobarbital, ketamine, and propofol were investigated. In addition, expression of HIF-2α protein was studied by immunoblotting. Hypoxia-induced EPO mRNA expression in the brain was significantly suppressed by isoflurane in a concentration-dependent manner. A similar effect was confirmed for all other general anesthetics. Hypoxia-inducible expression of HIF-2α protein was also significantly suppressed with isoflurane. In the experiments using primary cultured astrocytes, isoflurane, pentobarbital, and ketamine suppressed hypoxia-inducible expression of HIF-2α protein and EPO mRNA. Taken together, our results indicate that general anesthetics suppress activation of HIF-2 and inhibit hypoxia-induced EPO upregulation in the mouse brain through a direct effect on astrocytes.
    PLoS ONE 12/2011; 6(12):e29378. DOI:10.1371/journal.pone.0029378 · 3.23 Impact Factor
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    • "It might be speculated that the beta-fibrinogen gene -C148T polymorphism contributes to the etiology of perioperative stroke by modulating the fibrinogen and CRP expression. Perioperative strokes result in a prolonged hospital stay, increased rates of disability, and discharge to long-term care facilities [30]. "
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    ABSTRACT: The fibrinogen beta-chain (FGB) -C148T polymorphism is linked with plasma fibrinogen concentration in the general population. We examined whether the -C148T polymorphism is associated with pre- and early postoperative levels of fibrinogen, C-reactive protein (CRP), and interleukin-6 (IL-6) in 243 consecutive patients undergoing coronary artery bypass grafting (CABG) surgery. Plasma inflammatory markers were measured prior to and 5-7 days after surgery. The -C148T polymorphism was analyzed with the restriction fragment-length polymorphism method. The genotype distribution was as follows: CC-142 (58%), CT-85 (35%), and TT-16 (7%). Carriers of the -148T allele had higher preoperative plasma fibrinogen (4.42 ± 0.14 vs. 4.07 ± 0.11 mg/L, p = 0.04) and CRP levels (7.49 ± 1.2 vs. 4.26 ± 1.0 mg/L, p = 0.04) compared with non-carriers; 5 to 7 days after CABG, patients carrying -148T allele had increased CRP (70.4 ± 5.0 vs. 51.6 ± 4.25 mg/L, p = 0.005) and IL-6 levels (22.34 ± 2.64 vs. 15.53 ± 2.28 pg/L, p = 0.05), but not fibrinogen, compared with the remaining subjects. In-hospital nonfatal stroke occurred more frequently in -148T allele carriers (4% vs. 0%, p = 0.02). No genotype-associated differences were found in the occurrence of postoperative myocardial infarction and death. Presence of the -148T allele has also been associated with longer intensive care stay and intubation time (p = 0.01). Multivariate analysis identified the CT+TT genotype as an independent predictor of pre- and postoperative CRP levels. The results indicate that the presence of the -148T FGB allele determines higher pre- and postoperative levels of inflammatory markers, which might be associated with in-hospital clinical outcomes.
    Inflammation 04/2011; 35(2):429-35. DOI:10.1007/s10753-011-9332-6 · 2.21 Impact Factor
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