Dissociating the effects of oxygen pressure and content on the control of breathing and acute hypoxic response

Abstract

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 Po2 in 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.

Influence of high affinity haemoglobin on the response to normoxic and hypoxic exercise

“…8C and D) for a given workload, but this too was not different between groups. Recently, we found that resting chemosensitivity to acute hypoxia and hypercapnia was not different between controls and subjects with HAH (Dominelli et al 2019).…”

Peripheral chemoreflex control of fetal heart rate decelerations overwhelms the baroreflex during brief umbilical cord occlusions in fetal sheep

“…The peripheral chemoreflex is triggered by peripheral chemoreceptors located in the carotid bodies and aortic arch (Giussani et al 1993;Jensen & Hanson, 1995;Kumar & Prabhakar, 2012). P a,O 2 is classically considered the hypoxic stimulus, although there is evidence that arterial oxygen content may also be important, particularly at the aortic chemoreceptors (Kumar & Prabhakar, 2012;Dominelli et al 2019).…”

“… is classically considered the hypoxic stimulus, although there is evidence that arterial oxygen content may also be important, particularly at the aortic chemoreceptors (Kumar & Prabhakar, 2012; Dominelli et al . 2019).…”

Effects of impaired microvascular flow regulation on metabolism‐perfusion matching and organ function

“…Transfusion of blood with altered oxygen affinity may also serve to improve oxygen unloading in peripheral tissues. [288][289][290]…”

“…Furthermore, less tissue edema would likely result since more administered volume would be retained within the vasculature. Transfusion of blood with altered oxygen affinity may also serve to improve oxygen unloading in peripheral tissues 288‐290 …”