Central hemodynamic response during submaximal and exhaustive exercise in humans with high affinity hemoglobin and compensatory polycythemia

Humans with high affinity hemoglobin (HAH) develop compensatory polycythemia, an elevated hematocrit, which increases blood viscosity and may compromise cardiac output during exercise. In addition, humans with HAH have shown alterations in muscle blood flow during exercise in normoxia and hypoxia. As such, we aimed to investigate the influence of HAH and compensatory polycythemia on the central hemodynamic response during both normoxic and hypoxic exercise.Seven humans with HAH (4 females, 36 ± 13 years) and 11 healthy controls with normal oxygen binding affinity (4 females, 39 ± 10 years) performed cycling exercise at two intensities, 1) at a power output corresponding to 15% below normoxic gas exchange threshold (GET) for four minutes and 2) at a power output requiring 85% of normoxic maximal aerobic capacity until exhaustion. This protocol was performed during both normoxia and hypoxia (21% O2 and 15% O2 , respectively). Hemodynamic measurements were taken after three minutes of cycling at 15% below normoxic GET, three minutes at 85% V̇O2max , and at exhaustion. Cardiac output (Q̇) was estimated using an open-circuit acetylene wash-in technique. Stroke volume (SV) was calculated by dividing Q̇ by heart rate (HR). Baseline characteristics were compared between groups with student's two-tailed unpaired t-tests. Hemodynamics were analyzed using a two-way repeated measures analysis of variance to examine the effects of group and exercise intensity.As expected, hematocrit was ~15% greater in the HAH group than the control group (HAH: 58 ± 7 % vsCTL: 43 ± 3 %, P<0.001). Both groups elicited an increase in Q̇ and HR as exercise intensity increased during both normoxia (P<0.001 for both) and hypoxia (P<0.001 and P=0.002, respectively). There was no significant difference in Q̇ between groups during normoxia (P=0.85) or hypoxia (P=0.69). In addition, neither HR nor SV were different between groups during exercise in normoxia (P=0.13 and P=0.39, respectively) or hypoxia (P=0.89 and P=0.73, respectively). There was no group by intensity interaction for Q̇, HR, or SV during normoxia (all, P>0.42) or hypoxia (all, P>0.63).Our data suggest that cardiac output is not compromised during normoxic or hypoxic exercise in humans with HAH and compensatory polycythemia. Therefore, compensatory polycythemia may improve exercise capacity in humans with HAH by raising oxygen carrying capacity without limiting cardiac output.