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IMPACT OF INCREASED INTRAMUSCULAR PERFUSION HETEROGENEITY ON SKELETAL MUSCLE MICROVASCULAR HEMATOCRIT IN THE METABOLIC SYNDROME

Butcher, Joshua and Stanley, Shyla and Brooks, Steven and Chantler, Paul and Wu, Fan and Frisbee, Jefferson (2014) IMPACT OF INCREASED INTRAMUSCULAR PERFUSION HETEROGENEITY ON SKELETAL MUSCLE MICROVASCULAR HEMATOCRIT IN THE METABOLIC SYNDROME. Microcirculation, 21 (8). pp. 677-687.

Abstract

Objective: To determine the microvascular hematocrit (HMV) and permeability-surface area product (PS) in skeletal muscle of obese Zucker rats (OZR) and to evaluate the cumulative impact of increased microvascular perfusion heterogeneity in metabolic syndrome on mass transport/exchange constraints. Methods: The in situ self-perfused gastrocnemius muscle from OZR and lean Zucker rats (LZR) was examined under control conditions and following pre-treatment with TEMPOL (antioxidant)/SQ-29548 (PGH2/TxA2 receptor antagonist), phentolamine (adrenergic antagonist), or all three agents combined. A spike input of a labelled blood tracer cocktail was injected into the perfusing feed artery. Tracer washout was analyzed using models for HMV and PS. For a higher level of resolution, capillary hematocrit (HT) was determined in in situ cremaster muscle of OZR and LZR using videomicroscopy and direct cell counting. Results: Using tracer washout, HMV was decreased in OZR vs. LZR. While TEMPOL/SQ-29548 or phentolamine had only minor effects, treatment with all three agents improved HMV in OZR. HT in cremasteric microvessels was not different between strains, although variability was significantly increased in OZR, and was normalized following treatment with all three agents. PS was reduced in OZR and was not impacted by intervention, reflecting a reduced surface area for exchange. Conclusions: The increased heterogeneity in microvascular perfusion in OZR reduces aggregate HMV in skeletal muscle vascular networks and increases its variability and contributing to premature muscle fatigue. While targeted interventions can ameliorate this, the reduction in microvascular surface area is not reversible in an acute time frame.

Item Type: Article
Keywords: microcirculation, peripheral vascular disease, rodent models of metabolic syndrome, regulation of skeletal muscle blood flow, microvascular hemodynamics
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/20999

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