Carbon Dioxide Concentration Alters the Dynamics of Oxygen-Mediated Capillary Blood Flow Responses in Skeletal Muscle

We hypothesize that the dynamics of O₂-mediated blood flow responses in skeletal muscle capillaries are altered under different tissue carbon dioxide concentrations ([CO₂]) due to the interaction of overlapping mechanisms.

Eight male Sprague Dawley rats (164-215 g) were anesthetized and instrumented for systemic monitoring. The extensor digitorum longus muscle was isolated and reflected over a microfluidic gas exchange chamber mounted in an inverted microscope stage. 4-min intravital video recordings of capillary blood flow during O₂ challenges consisted of a 1-min baseline at 7% O₂ concentration ([O₂]), followed by 3 min at 2% [O₂], under constant background [CO₂] at 2%, 5%, and 8%. Recordings were analyzed offline using custom MATLAB software. Time transients (τ) of capillary hemodynamic responses were determined using a least squared regression fit to single- and double-exponential models.

Fast component τ of the O₂-mediated capillary red blood cell (RBC) velocity response was 2.1 s for 2% [CO₂], 3.8 s for 5% [CO₂], and 7.0 s for 8% [CO₂]. Third minute low [O₂] capillary RBC supply rate increases from baseline were greater for 8% [CO₂] (5% [CO₂]: 6.4 ± 8.7 cells/s vs. 8% [CO₂]: 8.5 ± 10.7 cells/s, p = 0.0007).

The fast component τ of O₂-mediated capillary hemodynamic responses was found to be slower with increasing background tissue [CO₂], suggesting that multiple interacting mechanisms are involved to appropriately regulate O₂ delivery under different CO₂ conditions in partial support of the hypothesis.