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

Paolo B. Dominelli, Sarah E. Baker, Chad C. Wiggins, Glenn M. Stewart, Pavol Sajgalik, John R.A. Shepherd, Shelly K. Roberts, Tuhin K. Roy, Timothy B. Curry, James D. Hoyer, Jennifer L. Oliveira, Glen E. Foster, Michael J. Joyner

Research output: Contribution to journalArticle

Abstract

Arterial oxygen tension and oxyhemoglobin saturation (SaO2 ) 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 highaffinity hemoglobin [HAH; partial pressure at 50% SaO2 (P50) = 16 ± 0.4 mmHg] causing greater SaO2 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 SaO2 . 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 SaO2. 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.

Original languageEnglish (US)
Pages (from-to)1622-1631
Number of pages10
JournalJournal of applied physiology
Volume127
Issue number6
DOIs
StatePublished - Jan 1 2019

Fingerprint

Respiration
Oxygen
Pressure
Partial Pressure
Hemoglobins
Heart Rate
Hypercapnia
Hemoglobinopathies
Oxyhemoglobins
Hypoxia
Ventilation
Arterial Pressure
Gases

Keywords

  • Heart rate
  • High-affinity hemoglobin
  • Ventilation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Dissociating the effects of oxygen pressure and content on the control of breathing and acute hypoxic response. / Dominelli, Paolo B.; Baker, Sarah E.; Wiggins, Chad C.; Stewart, Glenn M.; Sajgalik, Pavol; Shepherd, John R.A.; Roberts, Shelly K.; Roy, Tuhin K.; Curry, Timothy B.; Hoyer, James D.; Oliveira, Jennifer L.; Foster, Glen E.; Joyner, Michael J.

In: Journal of applied physiology, Vol. 127, No. 6, 01.01.2019, p. 1622-1631.

Research output: Contribution to journalArticle

Dominelli, PB, Baker, SE, Wiggins, CC, Stewart, GM, Sajgalik, P, Shepherd, JRA, Roberts, SK, Roy, TK, Curry, TB, Hoyer, JD, Oliveira, JL, Foster, GE & Joyner, MJ 2019, 'Dissociating the effects of oxygen pressure and content on the control of breathing and acute hypoxic response', Journal of applied physiology, vol. 127, no. 6, pp. 1622-1631. https://doi.org/10.1152/japplphysiol.00569.2019
Dominelli, Paolo B. ; Baker, Sarah E. ; Wiggins, Chad C. ; Stewart, Glenn M. ; Sajgalik, Pavol ; Shepherd, John R.A. ; Roberts, Shelly K. ; Roy, Tuhin K. ; Curry, Timothy B. ; Hoyer, James D. ; Oliveira, Jennifer L. ; Foster, Glen E. ; Joyner, Michael J. / Dissociating the effects of oxygen pressure and content on the control of breathing and acute hypoxic response. In: Journal of applied physiology. 2019 ; Vol. 127, No. 6. pp. 1622-1631.
@article{c5b2c8966c1746e2880cbe080ccf1caa,
title = "Dissociating the effects of oxygen pressure and content on the control of breathing and acute hypoxic response",
abstract = "Arterial oxygen tension and oxyhemoglobin saturation (SaO2 ) 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 highaffinity hemoglobin [HAH; partial pressure at 50{\%} SaO2 (P50) = 16 ± 0.4 mmHg] causing greater SaO2 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 SaO2 . 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 SaO2. 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.",
keywords = "Heart rate, High-affinity hemoglobin, Ventilation",
author = "Dominelli, {Paolo B.} and Baker, {Sarah E.} and Wiggins, {Chad C.} and Stewart, {Glenn M.} and Pavol Sajgalik and Shepherd, {John R.A.} and Roberts, {Shelly K.} and Roy, {Tuhin K.} and Curry, {Timothy B.} and Hoyer, {James D.} and Oliveira, {Jennifer L.} and Foster, {Glen E.} and Joyner, {Michael J.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1152/japplphysiol.00569.2019",
language = "English (US)",
volume = "127",
pages = "1622--1631",
journal = "Journal of Applied Physiology",
issn = "8750-7587",
publisher = "American Physiological Society",
number = "6",

}

TY - JOUR

T1 - Dissociating the effects of oxygen pressure and content on the control of breathing and acute hypoxic response

AU - Dominelli, Paolo B.

AU - Baker, Sarah E.

AU - Wiggins, Chad C.

AU - Stewart, Glenn M.

AU - Sajgalik, Pavol

AU - Shepherd, John R.A.

AU - Roberts, Shelly K.

AU - Roy, Tuhin K.

AU - Curry, Timothy B.

AU - Hoyer, James D.

AU - Oliveira, Jennifer L.

AU - Foster, Glen E.

AU - Joyner, Michael J.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Arterial oxygen tension and oxyhemoglobin saturation (SaO2 ) 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 highaffinity hemoglobin [HAH; partial pressure at 50% SaO2 (P50) = 16 ± 0.4 mmHg] causing greater SaO2 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 SaO2 . 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 SaO2. 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.

AB - Arterial oxygen tension and oxyhemoglobin saturation (SaO2 ) 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 highaffinity hemoglobin [HAH; partial pressure at 50% SaO2 (P50) = 16 ± 0.4 mmHg] causing greater SaO2 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 SaO2 . 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 SaO2. 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.

KW - Heart rate

KW - High-affinity hemoglobin

KW - Ventilation

UR - http://www.scopus.com/inward/record.url?scp=85076194441&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85076194441&partnerID=8YFLogxK

U2 - 10.1152/japplphysiol.00569.2019

DO - 10.1152/japplphysiol.00569.2019

M3 - Article

C2 - 31647724

AN - SCOPUS:85076194441

VL - 127

SP - 1622

EP - 1631

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

SN - 8750-7587

IS - 6

ER -