Skip to main content

Advertisement

SpringerLink
Log in

Pulmonary hemodynamics responses to hypoxia and/or CO2 inhalation during moderate exercise in humans

  • Integrative Physiology
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

In this study, we hypothesized that adding CO2 to an inhaled hypoxic gas mixture will limit the rise of pulmonary artery pressure (PAP) induced by a moderate exercise. Eight 20-year-old males performed four constant-load exercise tests on cycle at 40% of maximal oxygen consumption in four conditions: ambient air, normobaric hypoxia (12.5% O2), inhaled CO2 (4.5% CO2), and combination of hypoxia and inhaled CO2. Doppler echocardiography was used to measure systolic (s)PAP, cardiac output (CO). Total pulmonary resistance (TPR) was calculated. Arterialized blood pH was 7.40 at exercise in ambient and hypoxia conditions, whereas CO2 inhalation and combined conditions showed acidosis. sPAP increases from rest in ambient air to exercise ranged as follows: ambient + 110%, CO2 inhalation + 135%, combined + 184%, hypoxia + 217% (p < 0.001). CO was higher when inhaling O2-poor gas mixtures with or without CO2 (~ 17 L min−1) than in the other conditions (~ 14 L min−1, p < 0.001). Exercise induced a significant decrease in TPR in the four conditions (p < 0.05) but less marked in hypoxia (− 19% of the resting value in ambient air) than in ambient (− 33%) and in both CO2 inhalation and combined condition (− 29%). We conclude that (1) acute CO2 inhalation did not significantly modify pulmonary hemodynamics during moderate exercise. (2) CO2 adjunction to hypoxic gas mixture did not modify CO, despite a higher CaO2 in combined condition than in hypoxia. (3) TPR was lower in combined than in hypoxia condition, limiting sPAP increase in combined condition.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

CaO2 (or CO2):

Arterial oxygen (or carbon dioxide) content

CO:

Cardiac output

ΔPmax:

Tricuspid valve maximal gradient

FIO2 or FICO2 :

Fraction of inspired oxygen or carbon dioxide

HPV:

Hypoxic pulmonary vasoconstriction

NO:

Nitric oxide

PAO2 :

Alveolar pressure in oxygen

PaO2 :

Arterial pressure in oxygen

PvO2 :

Mixed venous blood pressure in oxygen

PAP:

Pulmonary artery pressure

s:

Systolic

m:

Mean

PETCO2 :

End-tidal partial pressure in carbon dioxide

PVR:

Pulmonary vascular resistance

R:

Respiratory exchange ratio

RAP:

Right atrial pressure

RV:

Right ventricle

TPR:

Total pulmonary resistance

TRV:

Tricuspid regurgitation velocity

VCO2 :

Carbon dioxide output

VE:

Minute ventilation

VO2 :

Oxygen consumption

VO2max:

Maximal oxygen consumption

References

  1. Adami A, Fagoni N, Ferretti G (2014) The Q-V O2 diagram: an analytical interpretation of oxygen transport in arterial blood during exercise in humans. Respir Physiol Neurobiol 193:55–61. https://doi.org/10.1016/j.resp.2014.01.007

    Article  PubMed  Google Scholar 

  2. Agusti AG, Rodriguez-Roisin R (1993) Effect of pulmonary hypertension on gas exchange. Eur Respir J 6:1371–1377

    PubMed  CAS  Google Scholar 

  3. Balanos GM, Pugh K, Frise MC, Dorrington KL (2015) Exaggerated pulmonary vascular response to acute hypoxia in older men. Exp Physiol 100:1187–1198. https://doi.org/10.1113/EP085403

    Article  PubMed  Google Scholar 

  4. Balanos GM, Talbot NP, Dorrington KL, Robbins PA (2003) Human pulmonary vascular response to 4 h of hypercapnia and hypocapnia measured using Doppler echocardiography. J Appl Physiol 94:1543–1551. https://doi.org/10.1152/japplphysiol.00890.2002

    Article  PubMed  Google Scholar 

  5. Barer GR, Shaw JW (1971) Pulmonary vasodilator and vasoconstrictor actions of carbon dioxide. J Physiol 213:633–645

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Brimioulle S, Lejeune P, Vachiery JL, Leeman M, Melot C, Naeije R (1990) Effects of acidosis and alkalosis on hypoxic pulmonary vasoconstriction in dogs. Am J Phys 258:H347–H353

    CAS  Google Scholar 

  7. Chemla D, Castelain V, Humbert M, Hebert JL, Simonneau G, Lecarpentier Y, Herve P (2004) New formula for predicting mean pulmonary artery pressure using systolic pulmonary artery pressure. Chest 126:1313–1317. https://doi.org/10.1378/chest.126.4.1313

    Article  PubMed  Google Scholar 

  8. Crocker GH, Toth B, Jones JH (2013) Combined effects of inspired oxygen, carbon dioxide, and carbon monoxide on oxygen transport and aerobic capacity. J Appl Physiol 115:643–652. https://doi.org/10.1152/japplphysiol.01407.2012

    Article  PubMed  CAS  Google Scholar 

  9. Croft QP, Formenti F, Talbot NP, Lunn D, Robbins PA, Dorrington KL (2013) Variations in alveolar partial pressure for carbon dioxide and oxygen have additive not synergistic acute effects on human pulmonary vasoconstriction. PLoS One 8:e67886. https://doi.org/10.1371/journal.pone.0067886

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Deem S (2004) Nitric oxide scavenging by hemoglobin regulates hypoxic pulmonary vasoconstriction. Free Radic Biol Med 36:698–706. https://doi.org/10.1016/j.freeradbiomed.2003.11.025

    Article  PubMed  CAS  Google Scholar 

  11. Deem S, Hedges RG, Kerr ME, Swenson ER (2000) Acetazolamide reduces hypoxic pulmonary vasoconstriction in isolated perfused rabbit lungs. Respir Physiol 123:109–119

    Article  PubMed  CAS  Google Scholar 

  12. Dorrington KL, Balanos GM, Talbot NP, Robbins PA (2010) Extent to which pulmonary vascular responses to PCO2 and PO2 play a functional role within the healthy human lung. J Appl Physiol 108:1084–1096. https://doi.org/10.1152/japplphysiol.90963.2008

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Dorrington KL, Talbot NP (2004) Human pulmonary vascular responses to hypoxia and hypercapnia. Arch Eur J Physiol 449:1–15. https://doi.org/10.1007/s00424-004-1296-z

    Article  CAS  Google Scholar 

  14. Doutreleau S, Enache I, Pistea C, Favret F, Lonsdorfer E, Dufour S, Charloux A (2017) Cardio-respiratory responses to hypoxia combined with CO2 inhalation during maximal exercise. Respir Physiol Neurobiol 235:52–61. https://doi.org/10.1016/j.resp.2016.09.012

    Article  PubMed  Google Scholar 

  15. Dunham-Snary KJ, Wu D, Sykes EA, Thakrar A, Parlow LR, Mewburn JD, Parlow JL, Archer SL (2017) Hypoxic pulmonary vasoconstriction: from molecular mechanisms to medicine. Chest 151:181–192. https://doi.org/10.1016/j.chest.2016.09.001

    Article  PubMed  Google Scholar 

  16. Fadel PJ (2015) Reflex control of the circulation during exercise. Scand J Med Sci Sports 25(Suppl 4):74–82. https://doi.org/10.1111/sms.12600

    Article  PubMed  Google Scholar 

  17. Fan JL, Kayser B (2013) The effect of adding CO2 to hypoxic inspired gas on cerebral blood flow velocity and breathing during incremental exercise. PLoS One 8:e81130. https://doi.org/10.1371/journal.pone.0081130

    Article  PubMed  PubMed Central  Google Scholar 

  18. Faoro V, Huez S, Vanderpool R, Groepenhoff H, de Bisschop C, Martinot JB, Lamotte M, Pavelescu A, Guenard H, Naeije R (2014) Pulmonary circulation and gas exchange at exercise in Sherpas at high altitude. J Appl Physiol 116:919–926. https://doi.org/10.1152/japplphysiol.00236.2013

    Article  PubMed  Google Scholar 

  19. Gordon JB, Rehorst-Paea LA, Hoffman GM, Nelin LD (1999) Pulmonary vascular responses during acute and sustained respiratory alkalosis or acidosis in intact newborn piglets. Pediatr Res 46:735–741

    Article  PubMed  CAS  Google Scholar 

  20. Harvey TC, Raichle ME, Winterborn MH, Jensen J, Lassen NA, Richardson NV, Bradwell AR (1988) Effect of carbon dioxide in acute mountain sickness: a rediscovery. Lancet 2:639–641

    Article  PubMed  CAS  Google Scholar 

  21. Herve P, Lau EM, Sitbon O, Savale L, Montani D, Godinas L, Lador F, Jais X, Parent F, Gunther S, Humbert M, Simonneau G, Chemla D (2015) Criteria for diagnosis of exercise pulmonary hypertension. Eur Respir J 46:728–737. https://doi.org/10.1183/09031936.00021915

    Article  PubMed  Google Scholar 

  22. Hoiland RL, Bain AR, Rieger MG, Bailey DM, Ainslie PN (2016) Hypoxemia, oxygen content, and the regulation of cerebral blood flow. Am J Physiol Regul Integr Comp Physiol 310:R398–R413. https://doi.org/10.1152/ajpregu.00270.2015

    Article  PubMed  Google Scholar 

  23. Hyman AL, Woolverton WC, Guth PS, Ichinose H (1971) The pulmonary vasopressor response to decreases in blood pH in intact dogs. J Clin Invest 50:1028–1043. https://doi.org/10.1172/JCI106574

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Ketabchi F, Egemnazarov B, Schermuly RT, Ghofrani HA, Seeger W, Grimminger F, Shid-Moosavi M, Dehghani GA, Weissmann N, Sommer N (2009) Effects of hypercapnia with and without acidosis on hypoxic pulmonary vasoconstriction. Am J Physiol Lung Cell Mol Physiol 297:L977–L983. https://doi.org/10.1152/ajplung.00074.2009

    Article  PubMed  CAS  Google Scholar 

  25. Kiely DG, Cargill RI, Lipworth BJ (1996) Effects of hypercapnia on hemodynamic, inotropic, lusitropic, and electrophysiologic indices in humans. Chest 109:1215–1221

    Article  PubMed  CAS  Google Scholar 

  26. Komori M, Takada K, Tomizawa Y, Nishiyama K, Kawamata M, Ozaki M (2007) Permissive range of hypercapnia for improved peripheral microcirculation and cardiac output in rabbits. Crit Care Med 35:2171–2175

    Article  PubMed  Google Scholar 

  27. Krampetz IK, Rhoades RA (1991) Intracellular pH: effect on pulmonary arterial smooth muscle. Am J Phys 260:L516–L521. https://doi.org/10.1152/ajplung.1991.260.6.L516

    Article  CAS  Google Scholar 

  28. Lee KJ, Hernandez G, Gordon JB (2003) Hypercapnic acidosis and compensated hypercapnia in control and pulmonary hypertensive piglets. Pediatr Pulmonol 36:94–101. https://doi.org/10.1002/ppul.10340

    Article  PubMed  Google Scholar 

  29. Marshall C, Lindgren L, Marshall BE (1984) Metabolic and respiratory hydrogen ion effects on hypoxic pulmonary vasoconstriction. J Appl Physiol Respir Environ Exerc Physiol 57:545–550

    PubMed  CAS  Google Scholar 

  30. Myers JL, Domkowski PW, Wang Y, Hopkins RA (1998) Sympathetic blockade blunts hypercapnic pulmonary arterial vasoconstriction in newborn piglets. Eur J Cardiothorac Surg 13:298–305

    Article  PubMed  CAS  Google Scholar 

  31. Naeije R, Brimioulle S (2001) Physiology in medicine: importance of hypoxic pulmonary vasoconstriction in maintaining arterial oxygenation during acute respiratory failure. Crit Care 5:67–71

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Naeije R, Chesler N (2012) Pulmonary circulation at exercise. Compr Physiol 2:711–741. https://doi.org/10.1002/cphy.c100091

    Article  PubMed  PubMed Central  Google Scholar 

  33. Naeije R, Dedobbeleer C (2013) Pulmonary hypertension and the right ventricle in hypoxia. Exp Physiol 98:1247–1256. https://doi.org/10.1113/expphysiol.2012.069112

    Article  PubMed  Google Scholar 

  34. Naeije R, Vanderpool R, Dhakal BP, Saggar R, Saggar R, Vachiery JL, Lewis GD (2013) Exercise-induced pulmonary hypertension: physiological basis and methodological concerns. Am J Respir Crit Care Med 187:576–583. https://doi.org/10.1164/rccm.201211-2090CI

    Article  PubMed  PubMed Central  Google Scholar 

  35. Oliveira RK, Agarwal M, Tracy JA, Karin AL, Opotowsky AR, Waxman AB, Systrom DM (2016) Age-related upper limits of normal for maximum upright exercise pulmonary haemodynamics. Eur Respir J 47:1179–1188. https://doi.org/10.1183/13993003.01307-2015

    Article  PubMed  Google Scholar 

  36. Penaloza D, Arias-Stella J (2007) The heart and pulmonary circulation at high altitudes: healthy highlanders and chronic mountain sickness. Circulation 115:1132–1146. https://doi.org/10.1161/CIRCULATIONAHA.106.624544

    Article  PubMed  Google Scholar 

  37. Raffestin B, McMurtry IF (1987) Effects of intracellular pH on hypoxic vasoconstriction in rat lungs. J Appl Physiol 63:2524–2531. https://doi.org/10.1152/jappl.1987.63.6.2524

    Article  PubMed  CAS  Google Scholar 

  38. Richardson DW, Wasserman AJ, Patterson JL Jr (1961) General and regional circulatory responses to change in blood pH and carbon dioxide tension. J Clin Invest 40:31–43. https://doi.org/10.1172/JCI104234

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Roach RC, Koskolou MD, Calbet JA, Saltin B (1999) Arterial O2 content and tension in regulation of cardiac output and leg blood flow during exercise in humans. Am J Phys 276:H438–H445

    CAS  Google Scholar 

  40. Robinson SM, Cadwallader JA, Hill PM (1979) Regional alveolar gas composition and lung function in sheep. Respir Physiol 37:239–254

    Article  PubMed  CAS  Google Scholar 

  41. Siebenmann C, Lundby C (2015) Regulation of cardiac output in hypoxia. Scand J Med Sci Sports 25(Suppl 4):53–59. https://doi.org/10.1111/sms.12619

    Article  PubMed  Google Scholar 

  42. Siebenmann C, Sorensen H, Jacobs RA, Haider T, Rasmussen P, Lundby C (2013) Hypocapnia during hypoxic exercise and its impact on cerebral oxygenation, ventilation and maximal whole body O(2) uptake. Respir Physiol Neurobiol 185:461–467. https://doi.org/10.1016/j.resp.2012.08.012

    Article  PubMed  Google Scholar 

  43. Subudhi AW, Olin JT, Dimmen AC, Polaner DM, Kayser B, Roach RC (2011) Does cerebral oxygen delivery limit incremental exercise performance? J Appl Physiol 111:1727–1734. https://doi.org/10.1152/japplphysiol.00569.2011

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Susmano A, Passovoy M, Carleton RA (1977) Mechanisms of hypercapneic pulmonary hypertension. Cardiovasc Res 11:440–445

    Article  PubMed  CAS  Google Scholar 

  45. Swenson ER, Robertson HT, Hlastala MP (1994) Effects of inspired carbon dioxide on ventilation-perfusion matching in normoxia, hypoxia, and hyperoxia. Am J Respir Crit Care Med 149:1563–1569. https://doi.org/10.1164/ajrccm.149.6.8004314

    Article  PubMed  CAS  Google Scholar 

  46. Sylvester JT, Shimoda LA, Aaronson PI, Ward JP (2012) Hypoxic pulmonary vasoconstriction. Physiol Rev 92:367–520. https://doi.org/10.1152/physrev.00041.2010

    Article  PubMed  CAS  Google Scholar 

  47. Viles PH, Shepherd JT (1968) Evidence for a dilator action of carbon dioxide on the pulmonary vessels of the cat. Circ Res 22:325–332

    Article  PubMed  CAS  Google Scholar 

  48. Viles PH, Shepherd JT (1968) Relationship between pH, Po2, and Pco2 on the pulmonary vascular bed of the cat. Am J Phys 215:1170–1176

    CAS  Google Scholar 

  49. Wright SP, Granton JT, Esfandiari S, Goodman JM, Mak S (2016) The relationship of pulmonary vascular resistance and compliance to pulmonary artery wedge pressure during submaximal exercise in healthy older adults. J Physiol 594:3307–3315. https://doi.org/10.1113/JP271788

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Yamaguchi K, Suzuki K, Naoki K, Nishio K, Sato N, Takeshita K, Kudo H, Aoki T, Suzuki Y, Miyata A, Tsumura H (1998) Response of intra-acinar pulmonary microvessels to hypoxia, hypercapnic acidosis, and isocapnic acidosis. Circ Res 82:722–728

    Article  PubMed  CAS  Google Scholar 

  51. Yamamoto Y, Nakano H, Ide H, Ogasa T, Takahashi T, Osanai S, Kikuchi K, Iwamoto J (2001) Role of airway nitric oxide on the regulation of pulmonary circulation by carbon dioxide. J Appl Physiol 91:1121–1130

    Article  PubMed  CAS  Google Scholar 

Download references

Funding

An ADIRAL (Association d’Aide aux Traitements à Domicile) research grant (2012 N1) supported the purchase of the AltiTrainer, SMTEC, Nyon, Switzerland.

Author information

Authors and Affiliations

  1. Service de Physiologie et d’Explorations Fonctionnelles, Pôle de Pathologie Thoracique, Hôpitaux Universitaires de Strasbourg, Equipe d’Accueil 3072, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France

    Stéphane Doutreleau, Irina Enache, Cristina Pistea, Bernard Geny & Anne Charloux

  2. Service de Physiologie et d’Explorations Fonctionnelles, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, BP 426, 1 Place de l’Hôpital, 67091, Strasbourg Cedex, France

    Anne Charloux

Authors
  1. Stéphane Doutreleau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Irina Enache
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cristina Pistea
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bernard Geny
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anne Charloux
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anne Charloux.

Ethics declarations

The study was approved by the Ethical Committee (Comité de Protection des Personnes “EST IV”, HUS No. 5546, NCT 01898858) of the University Hospitals of Strasbourg and conformed to the standards set by the Declaration of Helsinki.

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Doutreleau, S., Enache, I., Pistea, C. et al. Pulmonary hemodynamics responses to hypoxia and/or CO2 inhalation during moderate exercise in humans. Pflugers Arch - Eur J Physiol 470, 1035–1045 (2018). https://doi.org/10.1007/s00424-018-2127-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-018-2127-y

Keywords

Search

Navigation