Influence of local PO₂ on skeletal muscle microvascular blood flow during hyperinsulinemia

Wells, Brenda N (2022) Influence of local PO₂ on skeletal muscle microvascular blood flow during hyperinsulinemia. Masters thesis, Memorial University of Newfoundland.

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Abstract

The goal of this thesis was to test the hypothesis that insulin mediated hyperemia is partially dependent on local muscle oxygen concentration. To do so, microvascular blood flow was measured in response to varying imposed concentrations of oxygen in rat skeletal muscle. Sprague-Dawley rats were anesthetized, and the extensor digitorum longus (EDL) was reflected onto an inverted microscope. Intravital video microscopy sequences were recorded during baseline and hyperinsulinemic euglycemia. The muscle was reflected over a glass stage insert (Experiment 1a and 1b), or over a gas exchange chamber (Experiment 2), and microvascular capillary blood flow was recorded during sequential changes (7%-12%-2%-7%) of oxygen (O₂) concentration. Blood flow was measured by the red blood cell supply rate (SR) in number of cells per second. In Experiment 1a, supply rate (SR) increased from 8.0 to 14 cells/s at baseline to euglycemia (p = 0.01), while no significant SR variation was detected after performing a sham hyperinsulinemic euglycemic clamp (Experiment 1b). In Experiment 2, SR decreased at 12% O₂ and increased at 2% O₂, compared to 7% O₂, under both experimental conditions. SR responses to oxygen square wave oscillations during euglycemia were not different to those at baseline at each O₂ concentration (p > 0.9). Our results suggest the increase in blood flow observed in response to insulin is eliminated if tissue oxygen microenvironment is clamped at given oxygen concentrations. All animal protocols were approved by Memorial University’s Institutional Animal Care Committee.

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