Webb, Kevin L

AbstractFatiguing inspiratory work has been shown to evoke a sympathetically mediated reflex that has systemic cardiovascular consequences, including increases in heart rate and blood pressure and a decrease in resting limb vascular conductance. Moreover, the response to this reflex appears to be attenuated in females compared with males. It remains to be seen whether this respiratory muscle metaboreflex also exerts an effect on cerebral blood flow. Cerebral blood flow is tightly regulated to maintain homeostasis and critical function. Therefore, it stands to reason that cerebrovascular haemodynamics would not be compromised through this respiratory muscle metaboreflex. We hypothesized that fatiguing inspiratory work would reduce resting limb conductance, but cerebral blood flow would be minimally impaired. Females (34 ± 10 years old, n = 12) and males (31 ± 8 years old, n = 12) performed a 5 min, high‐intensity bout of inspiratory pressure threshold loading (IPTL) designed to evoke the respiratory muscle metaboreflex. In response to IPTL, mean arterial pressure increased in both males and females (p < 0.001), and limb vascular conductance decreased to a greater degree in males than in females (p = 0.005). The cerebrovascular conductance index was higher in females (p = 0.007) but not affected by IPTL (p = 0.417). Our findings suggest that cerebral blood flow is spared from the redistribution of blood flow in response to fatiguing inspiratory work and that this protection is true in both males and females.

AbstractOxygen transport from the lungs to peripheral tissue is dependent on the affinity of hemoglobin for oxygen. Recent experimental data have suggested that the maximum human capacity for oxygen uptake and utilization (V̇O2max) at sea level and altitude (~3000 m) is sensitive to alterations in hemoglobin‐oxygen affinity. However, the effect of such alterations on V̇O2max at extreme altitudes remains largely unknown due to the rarity of mutations affecting hemoglobin‐oxygen affinity. This work uses a mathematical model that couples pulmonary oxygen uptake with systemic oxygen utilization under conditions of high metabolic demand to investigate the effect of hemoglobin‐oxygen affinity on V̇O2max as a function of altitude. The model includes the effects of both diffusive and convective limitations on oxygen transport. Pulmonary oxygen uptake is calculated using a spatially‐distributed model that accounts for the effects of hematocrit and hemoglobin‐oxygen affinity. Systemic oxygen utilization is calculated assuming Michaelis–Menten kinetics. The pulmonary and systemic model components are solved iteratively to compute predicted arterial and venous oxygen levels. Values of V̇O2max are predicted for several values of hemoglobin‐oxygen affinity and hemoglobin concentration based on data from humans with hemoglobin mutations. The model predicts that increased hemoglobin‐oxygen affinity leads to increased V̇O2max at altitudes above ~4500 m.