Impact Of Cell-free Hemoglobin On Exercising Muscle Vascular Control In Rats

Abstract

Hemolysis associated with Sickle Cell Disease (SCD) compromises nitric oxide (NO) bioavailability and results in a plethora of cardiopulmonary and skeletal muscle complications causing severe exercise intolerance. Recent evidence suggests that cell-free Hb reduces NO bioavailability and lowers the skeletal muscle microvascular PO2 during contractions, likely due to a reduction in blood flow. Despite these observations, the effects of Hb on skeletal muscle vascular control during locomotory exercise remain unknown. PURPOSE: We tested the hypothesis that acute exposure to Hb would increase mean arterial pressure (MAP) and decrease hindlimb muscle blood flow in the exercising rat. METHODS: MAP and hindlimb skeletal muscle blood flow (fluorescent microspheres) were measured in male Sprague-Dawley rats (3-6 months, n=8) during submaximal treadmill running (20 ml/min, 5% grade) following a vehicle (0.2 ml of saline) and Hb (50 mg/kg) infusion. RESULTS: Relative to control, Hb resulted in a significantly greater exercising MAP (control: 137 ± 3, Hb: 150 ± 3 mmHg, p<0.05) and blood [lactate] (control: 2.51 ± 0.25, Hb: 3.13 ± 0.42 mM, p<0.05). Total exercising hindlimb skeletal muscle blood flow (control: 179 ± 14, Hb: 111 ± 7, ml/min/100 g, p<0.05) and vascular conductance (control: 1.34 ± 0.13, Hb: 0.75 ± 0.05 ml/min/100 g/mmHg, p<0.05) were lower following Hb infusion when compared to control. CONCLUSION: These data support the hypothesis that free Hb impairs vascular control and lowers skeletal muscle O2 delivery during exercise and provides a potential mechanism by which hemolytic diseases like SCD impair exercise tolerance in humans. Support: NIH-P30DK048520 (SKF), NIH-1R01HL125642-01A1 (DCI)