Increased Cerebral Oxygen Metabolism and Ischemic Stress in Subjects with Metabolic Syndrome-Associated Risk Factors: Pr
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Increased Cerebral Oxygen Metabolism and Ischemic Stress in Subjects with Metabolic Syndrome-Associated Risk Factors: Preliminary Observations Ken Uchino & Ridwan Lin & Syed F. Zaidi & Hiroto Kuwabara & Donald Sashin & Nicholas Bircher & Yue-Fang Chang & Maxim D. Hammer & Vivek Reddy & Tudor G. Jovin & Nirav Vora & Mouhammad Jumaa & Lori Massaro & Julia Billigen & Fernando Boada & Howard Yonas & Edwin M. Nemoto
Published online: 25 May 2010 # Springer Science+Business Media, LLC 2010
Abstract Hypertension, diabetes, obesity, and dyslipidemia are risk factors that characterize metabolic syndrome (MetS), which increases the risk for stroke by 40%. In a preliminary study, our aim was to evaluate cerebrovascular reactivity and oxygen metabolism in subjects free of vascular disease but with one or more of these risk factors. Volunteers (n=15) 59±15 (mean±SD)years of age clear of cerebrovascular disease by magnetic resonance angiography but with one or more risk factors were studied by quantitative positron emission tomography for measure-
ment of cerebral blood flow, oxygen consumption, oxygen extraction fraction (OEF), and acetazolamide cerebrovascular reactivity. Eight of ten subjects with MetS risk factors had OEF >50%. None of the five without risk factors had OEF >50%. The presence of MetS risk factors was highly correlated with OEF >50% by Fisher's exact test (p50% (elevated)
OEF 50% did not meet at least three of the five criteria to qualify as MetS as defined by the National Cholesterol Education Program ATPIII [23]. However, the absence of high OEF in those without these risk factors supports the notion that these risk factors may be linked to increased OEF secondary to an increase in CMRO2. This preliminary observation needs confirmation in a larger cohort of subjects that would allow identification of the components of MetS that are specifically associated with increased CMRO2 and OEF. The increased ischemic stress (high OEF) in these individuals is associated with increased CMRO2 but with normal or even exaggerated CVR, which provides some insight into the mechanism of increased OEF in the face of increased CMRO2. This suggests that the mechanism of ischemic stress is likely not related to atherosclerosis, vascular stenosis, or compromised collateral circulation but rather, an active vasoconstriction. Leptin stimulates brain metabolic rate [24, 25] and induces activation of the pituitary adrenal sympathetic system and the rennin-angiotensin system [26–30]. Increased plasma norephinephrine and angiontensin II causes vasoconstriction through NADPH oxidase [31]. Which also increases oxygen demand through activation of uncoupling of mitochondrial oxidative phosphorylation by uncoupling proteins [32, 33] activated by free fatty acids [34]. This sequence of events through NADPH oxidase could lead to injury-induced neointimal proliferation [35]. Since our study is a cross-sectional observation at one time point, the meaning of the high OEF in this population needs to be assessed in a cohort study with follow-up s
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