Foster, Glen E

Arterial oxygen tension and oxyhemoglobin saturation ([Formula: see text]) decrease in parallel during hypoxia. Distinguishing between changes in oxygen tension and oxygen content as the relevant physiological stimulus for cardiorespiratory alterations remains challenging. To overcome this, we recruited nine individuals with hemoglobinopathy manifesting as high-affinity hemoglobin [HAH; partial pressure at 50% [Formula: see text] (P50) = 16 ± 0.4 mmHg] causing greater [Formula: see text] at a given oxygen partial pressure compared with control subjects ( n = 12, P50 = 26 ± 0.4 mmHg). We assessed ventilatory and cardiovascular responses to acute isocapnic hypoxia, iso-oxic hypercapnia, and 20 min of isocapnic hypoxia (arterial Po2 = 50 mmHg). Blood gas alterations were achieved with dynamic end-tidal forcing. When expressed as a function of the logarithm of oxygen partial pressure, ventilatory sensitivity to hypoxia was not different between groups. However, there was a significant difference when expressed as a function of [Formula: see text]. Conversely, the rise in heart rate was blunted in HAH subjects when expressed as a function of partial pressure but similar when expressed as a function of [Formula: see text]. Ventilatory sensitivity to hypercapnia was not different between groups. During sustained isocapnic hypoxia, the rise in minute ventilation was similar between groups; however, heart rate was significantly greater in the controls during 3 to 9 min of exposure. Our results support the notion that oxygen tension, not content, alters cellular Po2in the chemosensors and drives the hypoxic ventilatory response. Our study suggests that in addition to oxygen partial pressure, oxygen content may also influence the heart rate response to hypoxia.NEW & NOTEWORTHY We dissociated the effects of oxygen content and pressure of cardiorespiratory regulation studying individuals with high-affinity hemoglobin (HAH). During hypoxia, the ventilatory response, expressed as a function of oxygen tension, was similar between HAH variants and controls; however, the rise in heart rate was blunted in the variants. Our work supports the notion that the hypoxic ventilatory response is regulated by oxygen tension, whereas cardiovascular regulation may be influenced by arterial oxygen content and tension.

AbstractReducing the work of breathing during exercise improves locomotor muscle blood flow and reduces diaphragm and locomotor muscle fatigue and is thought to be the result of a sympathetically mediated reflex.AimThe aim of this study was to assess muscle sympathetic nerve activity (MSNA) when the work of breathing is experimentally lowered during dynamic exercise.MethodsHealthy subjects (n = 12; age = 29 ± 9 years) performed semi‐recumbent cycling trials at 40%, 60%, and 80% of peak workload. Exercise trials consisted of spontaneous breathing, reduced work of breathing (proportional assist ventilator), followed by further spontaneous breathing (post‐ventilator). MSNA was recorded from the median nerve.ResultsThere was no difference in work of breathing between PAV and post‐PAV at 40% peak work. At 60% peak work, the ventilator significantly (P < 0.05) reduced work of breathing (103 ± 39 vs 144 ± 47 J min−1), sympathetic nerve activity (35 ± 5 vs 42 ± 8 burst min−1), and (2.4 ± 0.5 vs 2.6 ± 0.5 L min−1) without influencing ventilation (86 ± 9 vs 82 ± 10 L min−1; P > 0.05), for PAV and post‐PAV respectively. During 80% peak work (n = 8), the ventilator significantly (P < 0.05) reduced work of breathing (235 ± 110 vs. 361 ± 150 J min−1), MSNA (48 ± 7 vs 54 ± 11 burst min−1), and (2.9 ± 0.6 vs 3.2 ± 0.7 L min−1) but not ventilation (121 ± 20 vs 123 ± 20 L min−1; P > 0.05), for PAV and post‐PAV respectively. There was a significant relationship between MSNA and (P < 0.0001) with a significant interaction due to the ventilator (P < 0.05).ConclusionLowering the normally occurring work of breathing during exercise results in commensurate reductions in MSNA. Our findings provide evidence of a sympathetically mediated vasoconstrictor effect emanating from respiratory muscles during exercise.