Intermittent Hypoxia for Obstructive Sleep Apnea?

Letter to the Editor

Intermittent Hypoxia for ObstructiveSleep Apnea?

Gines Viscor,1 Antoni Ricart,2 Teresa Pages,1 Luisa Corral,2,3

Casimiro F. Javierre,3 and Josep L. Ventura3

Dear Editor:We are writing to you in relation to the excellent review

article by ER Swenson (2013) on hypoxic pulmonary va-soconstriction (HPV), describing how hypoxic vasocon-striction exists in the gas exchanging organs of mostly allvertebrate species, although it is well known that someauthors described a very blunted response in the cases ofyak and Tibetan people (Durmowicz et al., 1993; Groveset al., 1993). Not surprisingly, HPV shows a wide vari-ability between species and between normal humans andexhibits a complex process of modulating influences, suchas: 1) Erythrocytes: blood viscosity, Hb-O2 saturation-linked to blood cells microrheological changes; 2) Neuro-hormonal: peripheral chemoreceptor oxygen sensitivity; 3)Vascular endothelium: prostacyclin, CO; and 4) Others:acid-base status, inflammation. However, in this outstand-ing review we missed specific comments either to inter-mittent hypoxia (IH), the very common obstructive sleepapnea (OSA), or to chronic obstructive pulmonary disease(COPD).

Our group has been working for years with IH in a hypo-baric chamber and trying in the last years to carry out specificstudies in patients with OSA or COPD, not possible to do bythe prevention of pneumologists because of the supposedpossible negative effects of IH.

Very recently, Dale et al. (2014) published a review of themechanisms of IH benefits on the respiratory and non-respiratory functions, going deeply into the topic of both‘‘good’’ and ‘‘bad’’ effects, distinguishing the IH factorseliciting pathology versus physiological enhancement, andthat at least one factor is the IH ‘‘dose.’’

In our opinion, other major factors to consider in respect tothe possible ‘‘good’’ or ‘‘bad’’ effects of IH are the particularnature of hypoxia stimuli or even the presence of co-existingdisorders. It is crucial to take into account that people withOSA and mostly with COPD, often differ with the morestudied healthy people in the four aforementioned groups,conditions or factors that modulate the hypoxic ventilatoryresponse (HVR). For instance, in many cases of obstructivehypoxia, as in OSA or COPD, circulating carbon dioxidelevels increase as a consequence of the reduced pulmonary

gas exchange, then leading to acidosis, hypercapnia, cerebralvasodilation and, frequently, reduced consciousness. Now,take your pulsioximeter and travel to a high location such asthe Atacama Large Millimeter Array (ALMA) site (Chaj-nantor Plateau, Northern Chile, above 5000 m). Here you willfind the same level of arterial oxygen saturation but in anapparently healthy worker. Under such circumstances, peo-ple are alert and their increased hyperventilation leads tohypocapnia, alkalosis, and probably cerebral vascular con-striction. These examples clearly point out that is not ade-quate to consider hypoxia ‘‘per se’’ as a predictable factoreliciting the same physiological responses with the sameinvariant time course.

We have a lot to learn and discuss, but the term ‘‘inter-mittent hypoxia’’ seems too much broad as it includes severaldifferent (often opposite) physiological and pathologicalconditions.

We consider that the all-encompassing term ‘‘intermit-tent hypoxia’’ is nowadays confusing because it is indis-criminately applied to two different physiological situations.We propose to differentiate between hypercapnic ‘‘inter-mittent obstructive hypoxia’’ and hypocapnic ‘‘intermittentenvironmental hypoxia.’’

We would like to hear the authoritative opinion of the highaltitude medicine and biology community on the issuestreated in this letter. A very soon to be published review bySwenson (in press) will add interesting insights on thequestions raised in this letter and help to an in-depth dis-cussion of the matter.

Author Disclosure Statement

The authors declare no competing financial interests exist.

References

Dale EA, Ben Mabrouk F, Mitchell GS. (2014). Unexpectedbenefits of intermittent hypoxia: Enhanced respiratory andnonrespiratory motor function. Physiology (Bethesda, Md.)29:39–48.

Durmowicz AG, Hofmeister S, Kadyraliev TK, Aldashev AA,Stenmark KR. (1993). Functional and structural adaptation of

Departaments de 1Fisiologia i Immunologia, i 3Ciencies Fisiologiques II, Universitat de Barcelona, Barcelona, Spain.2Servei de Medicina Intensiva, Hospital Universitari de Bellvitge, L’Hospitalet, Spain.

HIGH ALTITUDE MEDICINE & BIOLOGYVolume 15, Number 4, 2014ª Mary Ann Liebert, Inc.DOI: 10.1089/ham.2014.1060

1

the yak pulmonary circulation to residence at high altitude. JAppl Physiol 74:2276–2285.

Groves BM, Droma T, Sutton JR, McCullough RG, McCul-lough RE, Zhuang J, Moore LG. (1993). Minimal hypoxicpulmonary hypertension in normal Tibetans at 3,658 m. JAppl Physiol 74:312–318.

Swenson ER. (2013). Hypoxic pulmonary vasoconstriction.High Alt Med Biol 14:101–110.

Swenson ER. (2014). Hypoxia and acid-base balance: Frommountains to malignancy. In: Hypoxia: Translation in Pro-gress. eds: Roach RC, Hackett PH. Springer, New York, (inpress).

Address correspondence to:Dr. Gines Viscor

Departament de Fisiologia i ImmunologiaUniversitat de Barcelona

Av. Diagonal 645Barcelona E-08028

Spain

E-mail: gviscor@ub.edu

Received March 7, 2014;accepted in final form July 6, 2014.

2 VISCOR ET AL.