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Objective: We sought to quantify how different muscle carbon dioxide concentrations (CO 2 ) alter the dynamics of oxygen-mediated blood flow responses in skeletal muscle capillaries. Methods: 6 male Sprague Dawley rats (164-215g) were anaesthetized, instrumented for systemic monitoring, and mechanically ventilated. The extensor digitorum longus muscle was isolated via blunt dissection, externalized, and reflected over a microfluidic gas exchange chamber mounted in the stage of an inverted microscope. Intravital video of capillary blood flow was recorded during 4-minute O 2 challenges consisting of a 1-minute baseline at 7% oxygen concentration (O 2 ), followed by 3 minutes at 2% O 2 . Before recordings, the muscle was equilibrated to constant background CO 2 of either 2%, 5%, or 8% for 5 minutes. Recordings were analyzed offline using custom MATLAB software. The time transients () of capillary hemodynamic responses were determined using a least-squared regression fit (LSRF) to single- and double-exponential models. All animal protocols were approved by Memorial University’s Animal Care Committee. Results: Baseline red blood cell (RBC) velocity was significantly different at 5% CO 2 (213.2±179.4 μm/s) compared to 2% CO 2 (177.7±162.6 μm/s, p=0.0016), and 8% CO 2 (250.3±193.6 μm/s, p<0.0001). RBC oxygen saturations (SO 2 ) were significantly different beyond 3 s post-baseline in all CO 2 conditions ( p<0.02, =3.2-4.3s). Minimum RBC SO 2 was 52%, 46%, and 38% below baseline at 12s, 14s, and 12s for 2%, 5%, and 8% CO 2 conditions, respectively. RBC velocity was significantly increased during 2% CO 2 by 3 s post-baseline (177.7±162.6 vs 188.7±168.6 μm/s, p<0.0001), during 5% CO 2 by 6 s post-baseline (213.2±179.4 vs 224.2±189.9 μm/s, p=0.0190), and during 8% CO 2 by 12 s post-baseline (250.3±193.6 vs 267.0±199.9 μm/s, p=0.0062). Time transients of the fast component of the oxygen-mediated velocity response, as determined by LSRF, were 1.9s for 2% CO 2 , 4.8s for 5% CO 2 , and 9.8s for 8% CO 2 . Velocity was increased at the end of the O 2 challenge by 39%, 33%, and 36% during 2%, 5%, and 8% CO 2 conditions, respectively. Baseline RBC supply rate (SR) was significantly different at 5% CO 2 (13.5±18.9 cells/s) compared to 2% CO 2 (9.5±15.3 cells/s, p=0.0090), and 8% CO 2 (19.0±23.6 cells/s, p<0.0001). At 2% CO 2 , SR increased significantly by 9 s post-baseline (9.5±15.2 vs 10.9±16.9 cells/s, p=0.0001), by 10 s post-baseline for 5% CO 2 (13.5±18.9 vs 14.9±20.6 cells/s, p=0.0099), and by 13 s post-baseline during 8% CO 2 (19.0±23.6 vs 21.1±25.2 cells/s, p=0.0204). The fast component of the oxygen-mediated SR response had a of 2.7s for 2% CO 2 , 4.5s for 5% CO 2 , and 6.9s for 8% CO 2 as determined by LSRF. Overall SR was increased by 74%, 51%, and 39% at the end of the O 2 challenge during 2%, 5%, and 8% CO 2 , respectively. As well, capillary hematocrits were significantly different during baseline at 5% CO 2 (21.4±16.1%) compared to 2% CO 2 (18.2±22.2%, p=0.0113), and 8% CO 2 (27.2±21.4%, p<0.0001). Conclusion: We have quantified the fast component of oxygen-mediated capillary hemodynamic responses to an acute decrease in skeletal muscle O 2 . The time transients of O 2 -mediated responses vary with tissue CO 2 such that increasing CO 2 results in slower response dynamics. As well, increasing background CO 2 provokes higher capillary RBC velocity, SR, and hematocrit both at baseline and during low O 2 challenges as expected. 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 2024 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.
Folkins et al. (Wed,) studied this question.