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Peripheral Chemoreceptor Responsiveness and Hypoxic Pulmonary Vasoconstriction. Tyler J. Albert, M.D. Senior Medical Resident Chief of Medicine Rounds November 23, 2010. 3 Years of Preparation. Intern year:

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peripheral chemoreceptor responsiveness and hypoxic pulmonary vasoconstriction

Peripheral Chemoreceptor Responsiveness and Hypoxic Pulmonary Vasoconstriction

Tyler J. Albert, M.D.

Senior Medical Resident

Chief of Medicine Rounds

November 23, 2010

3 years of preparation
3 Years of Preparation
  • Intern year:
    • Transformed outpatient rotations into transthoracic echocardiogram (TTE) practice sessions
  • R2 year:
    • Successfully ran the gauntlet of the VA IRB from Boise, ID
  • R3 year:
    • 8 weeks of research
important terminology
Important Terminology
  • Hypoxic ventilatory response (HVR):
    • Increase in ventilation due to a decrease in PaO2
    • Mediated by peripheral chemoreceptors in the carotid body and aortic arch
  • Isocapnic HVR:
    • Fixed CO2 levels, isolating hypoxemia
  • Poikilocapnic HVR:
    • Variable CO2 levels, physiologic but confounding
hypoxic pulmonary vasoconstriction hpv
Hypoxic Pulmonary Vasoconstriction (HPV)
  • Vasomotor response to alveolar hypoxia
  • Mediates ventilation/perfusion (V/Q) matching
    • optimizes PaO2 by reducing low V/Q fraction
  • Intrinsic to the lung
  • Focal with disease (PNA, atelectasis)
  • Global with hypoxia (altitude, hypoventilation)

Denervation of peripheral chemoreceptors in animals, diminishing HVR, increases HPV

Carotid body ablation

Chemical sympathectomy

Naeije et al. JAP 66:42, 1989


Individuals with high HVR

have less HPV in response to

low alveolar oxygen (PAO2).

methods measuring hvr
Methods: Measuring HVR
  • Recorded HVR (∆ minute ventilation/∆ SaO2)over 15 min of poikilocapnic hypoxia (0.21 to 0.12 FIO2)
  • Used nitrogen to drop the FIO2
  • Monitored:

- SaO2 - Minute ventilation

- HR - End-tidal CO2 (EtCO2)


methods measuring hpv
Methods: Measuring HPV
  • Screened for tricuspid regurgitation with TTE
  • Pulmonary artery systolic pressure (PASP) recorded by echosonographer
    • Bernoulli’s equation (∆P=4V2)
    • Subjects randomly at FIO2 = 0.21, 0.18, 0.15 and 0.12, each x 15 min
  • Echosonographer blinded to FIO2
  • PASP recorded at SaO2 = 85%
    • Provided a common PAO2 stimulus, using SaO2 as a surrogate for alveolar oxygenation
  • 15 healthy subjects
    • 11 men, 4 women
  • Age: 26-37, mean 29.4 years
  • Baseline SaO2: 95-98, mean 97%
  • Baseline EtCO2: 37-42, mean 39 mmHg
  • Baseline PASP: 14-30, mean 23 mmHg
  • Good range of HVRs (0.05-0.3 L/min/%SaO2)
    • Correlates with previously published data
  • EtCO2 dropped as expected with increasing HVR (p=0.035)
hvr correlates with hpv
HVR correlates with HPV

p = 0.01

R2 = 0.41

  • HVR and HPV are inversely related
    • Direct correlation between peripheral chemoreceptor response and hypoxic pulmonary vasoconstriction in healthy subjects
  • Consistent with animal models showing a modulating influence on HPV by peripheral chemoreceptor activation
  • First demonstration of this phenomenon in humans
  • Poikilocapnic HVR
    • Confounding from low CO2
    • Hypocapnia itself lowers HPV
  • Inaccuracy of TTE
    • Variable correlation with PASP by catheterization, does not measure pulmonary vascular resistance
    • VA IRB and subjects (co-residents) less likely to approve Swan-Ganz catheter
what s next
What’s Next
  • We identified a contributor to HPV, which could lead to targeted therapies
    • If isolated, we could stimulate breathing and alter pulmonary resistance in pulmonary hypertension, high altitude pulmonary edema, etc.
    • Almitrine: evidence for evoking increased carotid body activity
  • Oxford: customized chamber for isocapnic HVR and HPV measurement

Naeije R, LeJeune P, Leeman M, Melot C, Closset J. Pulmonary vascular responses to surgical chemodenervation and chemical sympathectomy in dogs. J Appl Physiol. 1989 Jan;66(1):42-50.

Steinback CD, Poulin MJ. Ventilatory responses to isocapnic and poikilocapnic hypoxia in humans. RespirPhysiolNeurobiol. 2007 Feb 15;155(2):104-13.

Dorrington KL, Talbot NP. Human pulmonary vascular responses to hypoxia and hypercapnia. Pflugers Arch. 2004 Oct;449(1):1-15. 

Duffin J. Measuring the ventilatory response to hypoxia. J Physiol. 2007 Oct 1;584(Pt 1):285-93.

Moudgil R, Michelakis ED, Archer SL. Hypoxic pulmonary vasoconstriction. J Appl Physiol. 2005 Jan;98(1):390-403. 

Teppema LJ, Dahan A. The ventilatory response to hypoxia in mamals: mechanisms, measurement, and analysis. Physiol Rev. 2010;90:675-754.

Aaronson PI, Robertson TP, Knock GA, et al. Hypoxic pulmonary vasoconstriction: mechanisms and controversies. J Physiol. 2006;570(1):53-58.

thank you
Thank you

Erik Swenson

Patricia Sills

VA Respiratory Therapists

New Saigon Deli

Andy Luks