(605.40) Impact of cell-free hemoglobin on oxygen pressure dynamics in muscles comprised primarily of fast-twitch fibers

Poster Board Number: E520

Edward Calvo (University of Hawaii, Hilo, University of Hawaii, Manoa), Kaiea Vera (University of Hawaii, Hilo), Ann Hashimoto (University of Hawaii, Manoa), Scott Ferguson (University of Hawaii, Hilo, University of Hawaii, Manoa)

Cell free hemoglobin (Hb), released due to hemolysis, reduces the bioavailability of nitric oxide (NO) and the microvascular PO2 (PO2mv, the pressure head that facilitates blood-myocyte O2 flux) during contractions in mixed fiber-type skeletal muscle. Despite the known impacts of cell-free Hb on mixed fiber type muscles, its effect within muscles composed primarily of fast-twitch fibers remains unknown. Thus, the purpose of this investigation was to test the hypothesis that cell free Hb would lower the PO2mv in the white (fast-twitch) portion of the gastrocnemius muscle during muscle contractions with no effect at rest or during the rest-contraction transition. Six young-adult male Sprague-Dawley rats had the white portion of the gastrocnemius muscle surgically exposed (100% type IIb + dx). PO2mv was measured at rest and during 180 s of electrically induced contractions (1 Hz, 6-8 v) under control and following 50 mg of Hb infusion (tail-artery catheter). Hb resulted in a 48% increase in mean arterial pressure at the onset of muscle contractions (control: 97.16 ± 6.5, Hb 143.40 ± 9.0 mmHg, plt;0.01), significantly shortened time-delay (control 14.3 ± 2.0, Hb 4.8 ± 1.6 s, plt;0.02), and mean response time (control 24.9 ± 1.2, Hb 16.4 ± 2.0 s, plt;0.02). There were no between-condition differences in steady-state (control 10.4 ± 1.4, Hb 14.1 ± 1.4 mmHg, pgt;0.05) or baseline PO2mv (control 16.4  ± 0.2, Hb 19.1 ± 0.01). Acute exposure to cell-free Hb resulted in a faster fall in the PO2mv during the rest-contraction transition. However, despite a significant increase in mean arterial pressure, there were no differences in the PO2mv observed during the contracting steady state. These results suggest that cell free Hb significantly increases vascular resistance within fast-twitch muscle, which causes O2 delivery-to-utilization mismatch at the onset of muscle contractions. These findings provide a potential mechanism by which hemolytic diseases like sickle cell disease impair exercise tolerance. Given that slow-twitch muscles rely more heavily on NO to support O2 delivery at rest and during contractions, it is likely that the effects observed in the present investigation will be exacerbated in highly oxidative muscles.

NIH-NIGMS, IDeA Networks of Biomedical Research Excellence (INBRE), P20GM103466.
Robert C. Perry Fund of the Hawaii Community Foundation 21ADVC-109518