Letter to the Editor
HIGH ALTITUDE MEDICINE & BIOLOGY Volume 15, Number 4, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/ham.2014.1060
Intermittent Hypoxia for Obstructive Sleep Apnea? Gine´s Viscor,1 Antoni Ricart,2 Teresa Page`s,1 Luisa Corral,2,3 Casimiro F. Javierre,3 and Josep L. Ventura3
gas exchange, then leading to acidosis, hypercapnia, cerebral vasodilation and, frequently, reduced consciousness. Now, take your pulsioximeter and travel to a high location such as the Atacama Large Millimeter Array (ALMA) site (Chajnantor Plateau, Northern Chile, above 5000 m). Here you will find the same level of arterial oxygen saturation but in an apparently healthy worker. Under such circumstances, people are alert and their increased hyperventilation leads to hypocapnia, alkalosis, and probably cerebral vascular constriction. These examples clearly point out that is not adequate to consider hypoxia ‘‘per se’’ as a predictable factor eliciting the same physiological responses with the same invariant time course. We have a lot to learn and discuss, but the term ‘‘intermittent hypoxia’’ seems too much broad as it includes several different (often opposite) physiological and pathological conditions. We consider that the all-encompassing term ‘‘intermittent hypoxia’’ is nowadays confusing because it is indiscriminately applied to two different physiological situations. We propose to differentiate between hypercapnic ‘‘intermittent obstructive hypoxia’’ and hypocapnic ‘‘intermittent environmental hypoxia.’’ We would like to hear the authoritative opinion of the high altitude medicine and biology community on the issues treated in this letter. A very soon to be published review by Swenson (in press) will add interesting insights on the questions raised in this letter and help to an in-depth discussion of the matter.
Dear Editor: We are writing to you in relation to the excellent review article by ER Swenson (2013) on hypoxic pulmonary vasoconstriction (HPV), describing how hypoxic vasoconstriction exists in the gas exchanging organs of mostly all vertebrate species, although it is well known that some authors described a very blunted response in the cases of yak and Tibetan people (Durmowicz et al., 1993; Groves et al., 1993). Not surprisingly, HPV shows a wide variability between species and between normal humans and exhibits a complex process of modulating influences, such as: 1) Erythrocytes: blood viscosity, Hb-O2 saturationlinked to blood cells microrheological changes; 2) Neurohormonal: peripheral chemoreceptor oxygen sensitivity; 3) Vascular endothelium: prostacyclin, CO; and 4) Others: acid-base status, inflammation. However, in this outstanding review we missed specific comments either to intermittent hypoxia (IH), the very common obstructive sleep apnea (OSA), or to chronic obstructive pulmonary disease (COPD). Our group has been working for years with IH in a hypobaric chamber and trying in the last years to carry out specific studies in patients with OSA or COPD, not possible to do by the prevention of pneumologists because of the supposed possible negative effects of IH. Very recently, Dale et al. (2014) published a review of the mechanisms of IH benefits on the respiratory and nonrespiratory functions, going deeply into the topic of both ‘‘good’’ and ‘‘bad’’ effects, distinguishing the IH factors eliciting pathology versus physiological enhancement, and that at least one factor is the IH ‘‘dose.’’ In our opinion, other major factors to consider in respect to the possible ‘‘good’’ or ‘‘bad’’ effects of IH are the particular nature of hypoxia stimuli or even the presence of co-existing disorders. It is crucial to take into account that people with OSA and mostly with COPD, often differ with the more studied healthy people in the four aforementioned groups, conditions or factors that modulate the hypoxic ventilatory response (HVR). For instance, in many cases of obstructive hypoxia, as in OSA or COPD, circulating carbon dioxide levels increase as a consequence of the reduced pulmonary
Author Disclosure Statement
The authors declare no competing financial interests exist. References
Dale EA, Ben Mabrouk F, Mitchell GS. (2014). Unexpected benefits of intermittent hypoxia: Enhanced respiratory and nonrespiratory 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 3Cie`ncies Fisiologiques II, Universitat de Barcelona, Barcelona, Spain. 2 Servei de Medicina Intensiva, Hospital Universitari de Bellvitge, L’Hospitalet, Spain.
1
2
the yak pulmonary circulation to residence at high altitude. J Appl Physiol 74:2276–2285. Groves BM, Droma T, Sutton JR, McCullough RG, McCullough RE, Zhuang J, Moore LG. (1993). Minimal hypoxic pulmonary hypertension in normal Tibetans at 3,658 m. J Appl 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: From mountains to malignancy. In: Hypoxia: Translation in Progress. eds: Roach RC, Hackett PH. Springer, New York, (in press).
VISCOR ET AL.
Address correspondence to: Dr. Gines Viscor Departament de Fisiologia i Immunologia Universitat de Barcelona Av. Diagonal 645 Barcelona E-08028 Spain E-mail: [email protected] Received March 7, 2014; accepted in final form July 6, 2014.
HIGH ALTITUDE MEDICINE & BIOLOGY Volume 15, Number 4, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/ham.2014.1060
Intermittent Hypoxia for Obstructive Sleep Apnea? Gine´s Viscor,1 Antoni Ricart,2 Teresa Page`s,1 Luisa Corral,2,3 Casimiro F. Javierre,3 and Josep L. Ventura3
gas exchange, then leading to acidosis, hypercapnia, cerebral vasodilation and, frequently, reduced consciousness. Now, take your pulsioximeter and travel to a high location such as the Atacama Large Millimeter Array (ALMA) site (Chajnantor Plateau, Northern Chile, above 5000 m). Here you will find the same level of arterial oxygen saturation but in an apparently healthy worker. Under such circumstances, people are alert and their increased hyperventilation leads to hypocapnia, alkalosis, and probably cerebral vascular constriction. These examples clearly point out that is not adequate to consider hypoxia ‘‘per se’’ as a predictable factor eliciting the same physiological responses with the same invariant time course. We have a lot to learn and discuss, but the term ‘‘intermittent hypoxia’’ seems too much broad as it includes several different (often opposite) physiological and pathological conditions. We consider that the all-encompassing term ‘‘intermittent hypoxia’’ is nowadays confusing because it is indiscriminately applied to two different physiological situations. We propose to differentiate between hypercapnic ‘‘intermittent obstructive hypoxia’’ and hypocapnic ‘‘intermittent environmental hypoxia.’’ We would like to hear the authoritative opinion of the high altitude medicine and biology community on the issues treated in this letter. A very soon to be published review by Swenson (in press) will add interesting insights on the questions raised in this letter and help to an in-depth discussion of the matter.
Dear Editor: We are writing to you in relation to the excellent review article by ER Swenson (2013) on hypoxic pulmonary vasoconstriction (HPV), describing how hypoxic vasoconstriction exists in the gas exchanging organs of mostly all vertebrate species, although it is well known that some authors described a very blunted response in the cases of yak and Tibetan people (Durmowicz et al., 1993; Groves et al., 1993). Not surprisingly, HPV shows a wide variability between species and between normal humans and exhibits a complex process of modulating influences, such as: 1) Erythrocytes: blood viscosity, Hb-O2 saturationlinked to blood cells microrheological changes; 2) Neurohormonal: peripheral chemoreceptor oxygen sensitivity; 3) Vascular endothelium: prostacyclin, CO; and 4) Others: acid-base status, inflammation. However, in this outstanding review we missed specific comments either to intermittent hypoxia (IH), the very common obstructive sleep apnea (OSA), or to chronic obstructive pulmonary disease (COPD). Our group has been working for years with IH in a hypobaric chamber and trying in the last years to carry out specific studies in patients with OSA or COPD, not possible to do by the prevention of pneumologists because of the supposed possible negative effects of IH. Very recently, Dale et al. (2014) published a review of the mechanisms of IH benefits on the respiratory and nonrespiratory functions, going deeply into the topic of both ‘‘good’’ and ‘‘bad’’ effects, distinguishing the IH factors eliciting pathology versus physiological enhancement, and that at least one factor is the IH ‘‘dose.’’ In our opinion, other major factors to consider in respect to the possible ‘‘good’’ or ‘‘bad’’ effects of IH are the particular nature of hypoxia stimuli or even the presence of co-existing disorders. It is crucial to take into account that people with OSA and mostly with COPD, often differ with the more studied healthy people in the four aforementioned groups, conditions or factors that modulate the hypoxic ventilatory response (HVR). For instance, in many cases of obstructive hypoxia, as in OSA or COPD, circulating carbon dioxide levels increase as a consequence of the reduced pulmonary
Author Disclosure Statement
The authors declare no competing financial interests exist. References
Dale EA, Ben Mabrouk F, Mitchell GS. (2014). Unexpected benefits of intermittent hypoxia: Enhanced respiratory and nonrespiratory 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 3Cie`ncies Fisiologiques II, Universitat de Barcelona, Barcelona, Spain. 2 Servei de Medicina Intensiva, Hospital Universitari de Bellvitge, L’Hospitalet, Spain.
1
2
the yak pulmonary circulation to residence at high altitude. J Appl Physiol 74:2276–2285. Groves BM, Droma T, Sutton JR, McCullough RG, McCullough RE, Zhuang J, Moore LG. (1993). Minimal hypoxic pulmonary hypertension in normal Tibetans at 3,658 m. J Appl 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: From mountains to malignancy. In: Hypoxia: Translation in Progress. eds: Roach RC, Hackett PH. Springer, New York, (in press).
VISCOR ET AL.
Address correspondence to: Dr. Gines Viscor Departament de Fisiologia i Immunologia Universitat de Barcelona Av. Diagonal 645 Barcelona E-08028 Spain E-mail: [email protected] Received March 7, 2014; accepted in final form July 6, 2014.
