Dynamics of capillary blood flow responses to acute local changes in oxygen and carbon dioxide concentrations

Abstract

Objectives: We aimed to quantify the magnitude and time transients of capillary blood flow responses to acute changes in local oxygen concentration ([O2]), and carbon dioxide concentration ([CO2]) in skeletal muscle. Additionally, we sought to quantify the combined response to low [O2] and high [CO2] to mimic muscle microenvironment at the onset of exercise. Methods: 13 Sprague Dawley rats were anaesthetized, mechanically ventilated, and instrumented with indwelling catheters for systemic monitoring. The extensor digitorum longus muscle was blunt dissected and reflected over a microfluidic gas exchange chamber mounted in the stage of an inverted microscope. Four O2 challenges (7-12%, 12-7%, 7-2%, 2-7%), four CO2 challenges (5-0%, 0-5%, 5-10%, 10-5%), and a combined low O2 (7–2%) and high CO2 (5–10%) challenges were delivered to the muscle surface with simultaneous visualization of capillary blood flow responses. Recordings were made for each challenge over a 1-minute baseline period followed by a 2-minute step change. The combined challenge employed a 1-minute [O2] challenge followed by a 2-minute change in [CO2]. Analysis of intravital videos was completed offline using custom MATLAB software. Mean data for each sequence were fit using least-squared non-linear exponential models to determine the dynamics of each response. All animal protocols were approved by Memorial University’s Animal Care Committee. Results: Increased [O2] from 7-12% and 2-7% provoked significant increases in red blood cell (RBC) saturation (SO2) within 2 s with time constants of 1.01 and 1.27 s respectively. This increase was coupled with a significant decrease in RBC velocity and supply rate (SR) that occurred within 10 s. 7–2% [O2] challenges decreased capillary RBC SO2 within 2 s following the step change (46.53 ± 19.56% vs. 48.51 ± 19.02%, p < 0.0001, τ = 1.44 s), increased RBC velocity within 3 s (228.53 ± 190.39 μm/s vs. 235.74 ± 193.52 μm/s, p < 0.0003, τ = 35.54 s) with a 52% peak increase by the end of the challenge, hematocrit and RBC SR showed similar dynamics. 5–10% [CO2] challenges increased RBC velocity within 2 s following the step change (273.40 ± 218.06 μm/s vs. 276.75 ± 215.94 μm/s, p = 0.007, τ = 79.34s), with a 58% peak increase, with RBC SR and hematocrit showing similar dynamics. Decreased local [CO2] conditions from 5 to 0% caused a small yet significant decrease in RBC SO2 within 1 s (τ = 0.84 s) while RBC velocity decreased significantly within 3 s (τ = 18.88 s) with a 77% peak decrease. Combined [O2] and [CO2] challenges resulted in additive responses to all microvascular hemodynamic measures with a 103% peak velocity increase by the end of the collection period. Conclusion: Microvascular level changes in muscle [O2] and [CO2] provoked capillary hemodynamic responses with differing time transients. Simulating exercise via combined [O2] and [CO2] challenges demonstrated the independent and additive nature of local blood flow responses to these agents. This project was supported by a Natural Sciences and Engineering Research Council of Canada Discovery grant awarded to GMF. Student support was provided by Memorial University's School of Graduate Studies and Faculty of Medicine. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.