Distinct effects of cell-free hemoglobin on oxygen pressure dynamics of fast vs. slow twitch muscle

Abstract

Hemolysis occurs following exposure to environmental stressors (e.g., microgravity) and in hemolytic diseases (e.g., sickle cell disease). When released from the red blood cell, cell-free hemoglobin (Hb) reduces nitric oxide (NO) availability and impacts skeletal muscle microvascular oxygen pressure (PO2 mv) dynamics during contractions in mixed fiber type muscle. However, the impact of cell-free Hb on fast- vs. slow twitch muscles remains unknown. Thus, the purpose of this investigation was to test the hypothesis that cell free Hb would lower the PO2 mv in slow, but not fast, twitch muscle. Phosphorescence quenching was used on two groups of young-adult male Sprague-Dawley rats to measure PO2 mv of the gastrocnemius (n=10) and soleus (n=8) muscles. Measurements were made at rest and during 180 s of 1-Hz contractions (6-8 v) under control conditions and following 50 mg of Hb infusion (tail-artery catheter). Mean arterial pressure (MAP) was monitored via a femoral artery catheter. Cell-free Hb increased MAP by 48% in the gastrocnemius and soleus groups (gastrocnemius, control: 93 ± 14, Hb: 138 ± 15; soleus, control: 89 ± 10, Hb: 132 mmHg, p<0.01 for both). Hb resulted in a shorter time delay (control: 10.29 ± 6.38, Hb: 3.88 ± 3.06 s) and faster mean response time (control: 22.03 ± 5.82, Hb: 14.29 ± 4.18 s) at the onset of contractions for the gastrocnemius (p<0.05 for both). There were no significant Hb induced differences in any kinetic parameter in the soleus (p>0.05 for all). Contrary to our original hypothesis and despite significant increases in MAP, cell-free Hb did not alter the kinetic response or the contracting steady-state PO2 mv in the slow-twitch soleus muscle. However, the kinetic response during the crucial rest-exercise transition in the gastrocnemius was significantly faster following Hb infusion, suggesting that Hb disrupts QO2/VO2 matching in fast-twitch muscle. Given the ~48% greater MAP following Hb infusion, these results suggest that cell-free Hb may disrupt skeletal muscle vascular conductance during contractions but may not impact PO2 mv in a fiber-type specific manner. Robert C. Perry fund of the Hawai'i Community Foundation 21ADVC-109518 and NIH-L60HL134123 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.