Characterization of CO₂-mediated microvascular blood flow responses in skeletal muscle tissue and investigation of underlying mechanisms using direct CO₂ microenvironment perturbations

McCarthy, Meaghan A. (2022) Characterization of CO₂-mediated microvascular blood flow responses in skeletal muscle tissue and investigation of underlying mechanisms using direct CO₂ microenvironment perturbations. Masters thesis, Memorial University of Newfoundland.

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Abstract

Several vasoactive molecules are involved in coordinating microvascular blood flow with metabolic demand in skeletal muscle tissue; however, the involvement of some metabolites, such as carbon dioxide (CO₂), are not well-characterized. The objective of this thesis was to characterize CO₂-mediated microvascular blood flow responses in skeletal muscle tissue and investigate potential underlying mechanisms, including ATP-sensitive potassium ion (KATP) channels and oxygen saturation (SO₂)-dependent release of ATP from red blood cells (RBC). A microfluidic gas exchange chamber was used to impose rapid and direct changes in the tissue CO₂ concentration of the extensor digitorum longus muscle of Sprague-Dawley rats. IVVM video sequences of capillary blood flow were recorded and analyzed offline for hemodynamic (RBC velocity, supply rate (SR), hematocrit (Hct)) and RBC SO2 measurements using a custom MATLAB software. Rapid and significant changes in capillary RBC velocity and SR were observed following incremental increases and dynamic step-changes in tissue CO₂. The involvement of KATP channels was investigated following systemic administration of glibenclamide (GLI, 5 mg / kg) (KATP channel antagonist). The magnitude of capillary RBC velocity and SR responses to CO₂ perturbations decreased following GLI administration. SO₂ remained constant throughout various CO₂ perturbations during baseline and after treatment with GLI. These findings support a significant involvement of CO₂ in local microvascular blood flow regulation in skeletal muscle tissue, the presence of an SO₂-independent mechanism, and a partial dependence on KATP channel activation.

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