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

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 both low [O₂] and high [CO₂] to mimic muscle microenvironment changes 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 in the stage of an inverted microscope. Four O₂ challenges, four CO₂ challenges, and a combined low O₂ (7-2%) and high CO₂ (5-10%) challenges were delivered to the surface with simultaneous visualization of capillary blood flow responses. Recordings were made for each challenge over a 1-min baseline period followed by a 2-min step change. The combined challenge employed a 1-min [O₂] challenge followed by a 2-min change in [CO₂]. Mean data for each sequence were fit using least-squared non-linear exponential models to determine the dynamics of each response. Results: 7-2% [O₂] challenges decreased capillary RBC saturation 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 supply rate show 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 by the end of the challenge, supply rate and hematocrit show similar dynamics. 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. Data for mean responses and exponential fitting parameters are reported for all challenges. 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.