Erythrocytes and the regulation of human skeletal muscle blood flow and oxygen delivery: role of erythrocyte count and oxygenation state of haemoglobin

Abstract

Blood flow to dynamically contracting myocytes is regulated to match O(2) delivery to metabolic demand. The red blood cell (RBC) itself functions as an O(2) sensor, contributing to the control of O(2) delivery by releasing the vasodilators ATP and S-nitrosohaemoglobin with the offloading of O(2) from the haemoglobin molecule. Whether RBC number is sensed remains unknown. To investigate the role of RBC number, in isolation and in combination with alterations in blood oxygenation, on muscle and systemic perfusion, we measured local and central haemodynamics during one-legged knee-extensor exercise ( approximately 50% peak power) in 10 healthy males under conditions of normocythaemia (control), anaemia, anaemia + plasma volume expansion (PVX), anaemia + PVX + hypoxia, polycythaemia, polycythaemia + hyperoxia and polycythaemia + hypoxia, which changed either RBC count alone or both RBC count and oxyhaemoglobin. Leg blood flow (LBF), cardiac output (Q) and vascular conductance did not change with either anaemia or polycythaemia alone. However, LBF increased with anaemia + PVX (28 +/- 4%) and anaemia + PVX + hypoxia (46 +/- 6%) and decreased with polycythaemia + hyperoxia (18 +/- 5%). LBF and Q with anaemia + PVX + hypoxia (8.0 +/- 0.5 and 15.8 +/- 0.7 l min(-1), respectively) equalled those during maximal knee-extensor exercise. Collectively, LBF and vascular conductance were intimately related to leg arterial-venous (a-v) O(2) difference (r(2)= 0.89-0.93; P < 0.001), suggesting a pivotal role of blood O(2) gradients in muscle microcirculatory control. The systemic circulation accommodated to the changes in muscle perfusion. Our results indicate that, when coping with severe haematological challenges, local regulation of skeletal muscle blood flow and O(2) delivery primarily senses alterations in the oxygenation state of haemoglobin and, to a lesser extent, alterations in the number of RBCs and haemoglobin molecules.

Figure 1. Leg haemodynamics with alterations in RBC count and blood oxygenation

Leg haemodynamics and oxygenation during submaximal one-legged knee-extensor exercise (52–53 W (± 5 W)) in normocythaemia (control), anaemia, anaemia combined with plasma volume expansion (anaemia + PVX), anaemia combined with plasma volume expansion and hypoxia (anaemia + PVX + hypoxia), polycythaemia, polycythaemia combined with hyperoxia (polycythaemia + hyperoxia) and polycythaemia combined with hypoxia (polycythaemia + hypoxia). For comparison, haemodynamics and oxygenation data at rest and during peak one-legged knee-extensor exercise (95 ± 11 W) in the control condition are depicted. A, leg blood flow; B, mean arterial pressure; C, leg vascular conductance; D, leg O₂ delivery; E, leg a–v O₂ difference; F, leg . Data are means ± s.e.m. for 9 subjects. *Significantly different from control, P < 0.05.

Figure 2. Systemic haemodynamics with alterations in RBC count and blood oxygenation

Systemic haemodynamics and during submaximal one-legged knee-extensor exercise (52–53 W (± 5 W)) in normocythaemia (control), anaemia, anaemia + PVX, anaemia + PVX + hypoxia, polycythaemia, polycythaemia + hyperoxia and polycythaemia + hypoxia. For comparison, haemodynamics and oxygenation data at rest and during peak one-legged knee-extensor exercise (95 ± 11 W) in the control condition are depicted. A, cardiac output; B, heart rate; C, stroke volume; D, central venous pressure; E, systemic . Data are means ± s.e.m. for 8–10 subjects. *Significantly different from control, P < 0.05.

Figure 3. Blood flow and blood O₂

Relationships between leg and systemic blood flow versus a–v O₂ difference and arterial O₂ and Hb contents. Note the tight inverse relationships between leg and systemic blood flow versus a–v O₂ difference and arterial O₂ content, but the weak relationship with total Hb and RBC. A, leg blood flow and cardiac output versus a–v O₂ difference; B, leg blood flow and cardiac output versus RBC count; C, leg blood flow versus femoral venous O₂ content; D, leg blood flow and cardiac output versus arterial O₂ content; E, leg blood flow and cardiac output versus arterial Hb; F, leg blood flow versus femoral venous P_O2. Data are means ± s.e.m. for 9 subjects. *Significantly different from control, P < 0.05.

Figure 4. Partition of leg and systemic blood flow into RBC and plasma flows

Leg RBC and plasma flows during exercise (A) and at rest (B) and systemic RBC and plasma flows during exercise (C) and at rest (D) in the control, anaemia, anaemia + PVX, anaemia + PVX + hypoxia, polycythaemia + hyperoxia and polycythaemia + hypoxia conditions. Data are means ± s.e.m. for 9 subjects. *Significantly different from control, P < 0.05.