[PP.29.03] METABOLIC SYNDROME EXACERBATES ISCHEMIA AND REPERFUSION INJURY ON THE BRAIN MICROCIRCULATION OF RATS

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Abstract

Objective:

Metabolic Syndrome (MS) is characterized by a cluster of risk factors for cardiovascular diseases and is an independent risk factor for ischemic stroke. In this study we investigated the impact of the MS of brain ischemia and reperfusion (IR) outcomes on brain microcirculation of diet-induced MS in rats.

Design and method:

Forty-eighth Wistar Kyoto rats were fed with high-fat diet (HFD) submitted or not to 30 minutes of ischemia, through bilateral carotid occlusion, followed by 1 hour of reperfusion IR (HFD-IR or HFD-sham, respectively) or standard chow submitted or not to IR (CONT-IR or CONT-sham) for 20 weeks. Cerebral microcirculation flow was evaluated by Laser Speckle Contrast Imaging and the brain functional capillary density, endothelial-leukocyte interactions and endothelial function were evaluated by intravital microscopy.

Results:

The HFD group presented increases of systolic blood pressure (142 ± 7 mmHg p < 0.001), heart rate (431 ± 18bpm p < 0.001), fasting plasma glucose (224 ± 11 mg/dL p < 0.001) and insulin (6.5 ± 1.1 ng/ml p < 0.01 when compared to the CONT group (117 ± 8 mmHg, 349 ± 30 bpm, 97 ± 11 mg/dl and 24 ± 0.5 ng/ml, respectively). These effects were accompanied by decreases on blood perfusion in the brain (176 arbitrary perfusion units, APU) compared to control group (230 APU). HFD-IR group showed an exacerbated decrease in brain perfusion during the ischemia period and not returning to basal values after reperfusion period (basal 186 APU, ischemia 128 APU and reperfusion 206 APU). HFD group also presented a marked functional and structural capillary rarefaction, HFD Sham (182 ± 21 capillaries/mm2 p < 0.001) and HFD-IR (111 ± 19 capillaries/mm2 p < 0.001) vs. CONT-sham (325 ± 20capillaries/mm2). The number of rolling leukocytes was increased in HFD-sham (11 ± 0.4 cells/min p < 0.001), HFD-IR (11 ± 1 cells/min p < 0.001) and in CONT-IR (10 ± 1 cells/min p < 0.001) vs. CONT-sham (1 ± 0.6 cells/min). Endothelial-dependent vasodilation response to Ach was abolished in HFD-IR group when compared to CONT-sham (-17% vs 30% from baseline; respectively, p < 0.001). The malondialdehyde levels showed an increase of oxidative stress in all groups compared to CONT-sham.

Conclusions:

Our results demonstrated that animals with metabolic syndrome have functional, structural and inflammatory changes in the cerebral microcirculation resulting on defective recovery blood flow during brain IR.

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