Research

Intrapulmonary arteriovenous anastomoses (IPAVA)

The existence and functional significance of intrapulmonary arteriovenous anastomoses in cardio-pulmonary physiology and medicine remains controversial. Our lab has spent >15 years investigating the mechanisms regulating blood flow through intrapulmonary arteriovenous anastomoses and have recently provided evidence for significant roles in pulmonary gas exchange efficiency and increased pulmonary pressure in older humans. The significance of this work is that it continues to challenge the idea that all gas exchange inefficiency is primarily restricted to ventilation to perfusion heterogeneity and diffusion limitation. Additionally, our work has led to the discovery that blood flow through intrapulmonary arteriovenous anastomoses contributes to diseases such as stroke (Abushora et al., JASE, 2013); Beriberi heart (Nakano et al., AJRCCM 2013). Our lab group remains the leaders in the field for this research area as evidenced by our 2015 invited review on this subject in The Journal of Physiology.

Most significant publications in this area:

HC Norris, TS Mangum, JW, Duke, TB Straley, RD Goodman, JA Hawn & A.T. Lovering. Exercise- and hypoxia-induced blood flow through intrapulmonary arteriovenous anastomoses is reduced in older adults. J Appl Physiol 116: 1324-1333, 2014. PMID: 24627355

Elliott, J.E., JW Duke, JA Hawn, JR Halliwill & A.T. Lovering. Increased cardiac output, not pulmonary artery systolic pressure, increases intrapulmonary shunt in healthy humans at rest breathing room air and 40% O2. J Physiol 592 (20) 4537-4553, 2014. PMID: 25085889

Duke, JW, BJ Ryan, JT Davis, KM Beasley, J.E. Elliott, K.M. Beasley, JA Hawn, WC Byrnes, and AT Lovering. Decreased arterial PO2, not O2 content, increases blood flow through intrapulmonary arteriovenous anastomoses at rest. J Physiol 594 (17): 4981–4996, 2016. PMID:27062157

Petrassi, F.A., J.E. Davis, K.M. Beasley, N. Evero, J. E. Elliott, R.D. Goodman, J.E. Futral, A.W. Subudhi, J. Manuel Solano-Altamirano, Saul Goldman R.C. Roach, A.T. Lovering. AltitudeOmics: Effect of reduced barometric pressure on detection of intrapulmonary shunt, pulmonary gas exchange efficiency and total pulmonary resistance. J Appl Physiol 124(5): 1363-1376, 2018. doi: PMID:29357511

Patent foramen ovale (PFO)

Through our studies of intrapulmonary arteriovenous anastomoses, we have discovered the importance of another source of shunt: the patent foramen ovale (PFO). Data from several studies suggest that PFO is prevalent in ~25 to 40% of the general population, so its prevalence is not trivial. Our studies have also discovered that the PFO is not as insignificant as previously assumed. We have found physiologically and clinically significant and important differences in pulmonary gas exchange efficiency, core body temperature, pulmonary hypertension and stroke. Our lab group remains the leaders in the field for this research area as evidenced by our 2022 invited review on this subject in The Journal of Physiology.

Most significant publications in this area:

J.T. Davis, C-Y.A. Ng, S.D. Hill, R.C. Padgett and A.T. Lovering. Higher oesophageal temperature at rest and during exercise in humans with patent foramen ovale. J Physiol 593(20):4615-30, 2015. PMID: 26173096.

J.E. Elliott, S.S. Laurie, J.P. Kern, K.M. Beasley, R.D. Goodman, B. Kayser, A.W. Subudhi, R.C. Roach & A.T. Lovering. AltitudeOmics: Impaired pulmonary gas exchange efficiency and ventilatory acclimatization in humans with a PFO following 16 days at 5260 m. J Appl Physiol 118:1100-1112, 2015. PMID: 25678698

A.T. Lovering, M. Lozo, O. Barak, J.T. Davis, M. Lojpur, P. Lozo, K. Caljkusic, &, Z. Dujic. Resting arterial hypoxemia in patients with chronic heart failure, pulmonary hypertension and patent foramen ovale Exp Phsyiol 101 (5):657-670 2016. PMID: 26990684

Duke, JW, K.M. Beasley, J.P. Speros, J.E. Elliott, S.S. Laurie, R.D. Goodman, J.E. Futral, J.A. Hawn, and A.T. Lovering. Impaired pulmonary gas exchange efficiency, but normal pulmonary artery pressure increases, with hypoxia in men and women with a patent foramen ovale. Exp Physiol 105 (9) 1648-1659, 2020. PMID: 32627890

Environmental physiology & field research

Environmental stressors such as heat, altitude and diving provide a better understanding of how the human body can cope with challenges to homeostasis. Our lab has been active in environmental physiology since 2012. We have found significant physiological and clinical findings related to blood flow through intrapulmonary arteriovenous anastomoses and patent foramen ovale with respect to pulmonary hypertension, pulmonary gas exchange efficiency, acute mountain sickness susceptibility, thermoregulation and ventilatory responses to heat and cold. Our lab group remains the leaders in the field for this research area as evidenced by our 2016 and 2022 invited reviews on these subjects in The Journal of Applied Physiology and The Journal of Physiology, respectively.

Most significant publications in this area:

K. Sun , Y. Zhang , A. D'Alessandro , A. Song , H. Wu , H. Liu , M. Adebiyi , A. Huang , Y.E. Wen , M. Bogdanov , T. Nemkov , A. Vila , J. O'Brien , R. Kellems , W. Dowhan , A. Subudhi , S. Jameson-Van Houten , C. Julian , A.T. Lovering , M. Safo , K. Hansen , R. Roach, Y. Xia. Sphingosine 1 phosphate promotes erythrocyte glycolysis and oxygen release for adaptation to high altitude hypoxia. Nat Commun 15;7:12086. 2016. PMID:27417539

J.T. Davis, M.W. Hay, A.M. Hardin, M.D. White and A.T. Lovering. Effect of a patent foramen ovale in humans on thermal responses to passive cooling and heating. J Appl Physiol 123(6):1423-1432 2017. PMID:28819008

S.S. Laurie, K. Christian, J. Kysar, S.M.C. Lee, A.T. Lovering, B.R. Macias, S. Moestl, W. Sies, M. Young, and M.B. Stenger. Cerebrovascular CO2 Reactivity and Hypercapnic Ventilatory Response during Strict Head-down Tilt Bed Rest in a Mild Hypercapnic Environment. J Physiol. 598(12):2491-2505. 2020. PMID: 32196672

T. Kelly, C. Brown, M. Bryant-Ekstrand, R. Lord, T. Dawkins, A. Drane, O. Barak, T. Dragun, M. Stembridge, B. Spajić, I. Drviš, J.W. Duke, G.E. Foster, P.N. Ainslie, Ž. Dujić, and A.T. Lovering. Blunted hypoxic pulmonary vasoconstriction in apnoea divers. Exp Physiol 107(11):1225-1240, 2022.

Cardiopulmonary and respiratory sequelae of preterm birth

Cardiopulmonary outcomes in adults with a history of preterm birth are only beginning to be identified and understood. Our lab has produced some of the first data in this population identifying cardiopulmonary adult outcomes and examining the mechanisms responsible for those outcomes. We have identified normal pulmonary gas exchange efficiency, but abnormal airway and pulmonary vascular responses to exercise. The significance, innovation and impact of this work is evidenced by invitations to collaborate in this area with other groups (MacLean et al., Thorax, 2016), editorials on our work by leaders in the field of respiratory limitations to exercise in patients with obstructive lung disease (O’Donnell Annals ATS, 2014), citations in very high impact reviews (Islam et al., AJRCCM 2015; Bolton et al., Thorax, 2015) and invitation to speak and participate in an NIH-sponsored workshop on this topic. Our lab group remains the leaders in the field for this research area as evidenced by our 2022 invited review on this subject in The Journal of Physiology.

Most significant publications in this area:

Lovering, A.T., J.E. Elliott, S.S. Laurie, K.M. Beasley, C.E. Gust, T.S. Mangum, I.M. Gladstone and J.W. Duke. Ventilatory and sensory responses in adult survivors of preterm birth and bronchopulmonary dysplasia with reduced exercise capacity. Annals ATS 11(10) 1528-1537, 2014. PMID: 25380058.

S.S. Laurie, J.E. Elliott, K.M. Beasley, T.S. Mangum, R.D. Goodman, J.W. Duke, I.M. Gladstone & A.T. Lovering. Exaggerated Increase in Pulmonary Artery Pressure during Exercise in Adults Born Preterm. Am J Respir Crit Care Med 15;197(6):821-823. 2018. PMID: 28885857.

J.W. Duke, A. Zidron, I.M. Gladstone & A.T. Lovering. Alleviating mechanical constraints to ventilation with heliox improves exercise endurance in adult survivors of very preterm birth. Thorax 74(3): 302-304 2019. PMID:30217953

Analysis of maximal expiratory flow-volume curves in adult survivors of preterm birth. Y. Molgat-Seon, P.B. Dominelli, C.M. Peters, J.A. Guenette, A.W. Sheel, I.M. Gladstone, A.T. Lovering, & J.W. Duke Am J Physiol Regul Integr Comp Physiol 317(4): R588-R596, 2019. PMID: 31433666

Neural and chemical control of breathing

The neural control of breathing requires a well-coordinated neuro-motor behavioral response including the brainstem, chemoreceptors, musculoskeletal system and airways. The respiratory system is often disturbed in normal people during sleep and in many patient populations in wake and sleep. I have a longstanding interest in the control of breathing spanning single neuron recordings in animals to integrative ventilatory responses in humans. Currently my lab is working to identify the reasons why people with a PFO have blunted ventilatory responses to oxygen and carbon dioxide as well how sleep apneas and hypopneas may be contributing to neuro-ocular sequelae associated with long duration spaceflight. The significance, innovation and impact of this work is evidenced by editorials on our work by leaders in the field of respiratory control under environmental stressors (Day et al J Physiol 2020).

Most significant publications in this area:

Lovering, A.T., J.J. Fraigne, W.L. Dunin-Barkowski, E.H. Vidruk and J.M. Orem. Medullary respiratory neural activity during hypoxia in NREM and REM sleep in the cat. J Neurophysiol 95:803-810, 2006. PMID: 16192335

Lovering, A.T., J.J. Fraigne, E.H. Vidruk, W.L. Dunin-Barkowski and J.M. Orem. Tonic and phasic drive to medullary respiratory neurons during periodic breathing. Respiration Physiol & Neurobiol 181: 286-301, 2012. PMID: 22484379

J.T. Davis, L.M. Boulet, A.M. Hardin, A.J. Chang, G.E. Foster and A.T. Lovering. Effect of a patent foramen ovale on ventilatory responses during acute exposure to hypoxia and hypercapnia. J Appl Physiol 126: 730-738, 2019. PMID: 30521423