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Juan F. Masa, MD, PhD; Jaime Corral, MD; Javier Gómez-de-Terreros, MD, PhD; María-Ángeles Sánchez-Quiroga, MD; Babak Mokhlesi, MD, FCCP
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FINANCIAL/NONFINANCIAL DISCLOSURES: See earlier cited article for author conflicts of interest.

aPulmonary Section, San Pedro de Alcántara Hospital, Cáceres, Spain

bPulmonary Section, Virgen del Puerto Hospital, Plasencia, Spain

cDepartment of Medicine, Section of Pulmonary and Critical Care, University of Chicago, Chicago, IL

dCIBER de enfermedades respiratorias (CIBERES), Madrid, Spain

CORRESPONDENCE TO: Juan F. Masa, MD, PhD, Pulmonary Section, San Pedro de Alcántara Hospital, Avda. Pablo Naranjo S/N, 10003 Cáceres, Spain


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(6):1406-1407. doi:10.1016/j.chest.2016.09.036
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We are grateful to Dr Burtscher for his interest in our article “Protective Cardiovascular Effect of Sleep Apnea Severity in Obesity Hypoventilation Syndrome” published in CHEST (July 2016). Dr Burtscher poses two main questions: (1) Is the term ischemia preconditioning used appropriately in our study or rather should we be referring to hypoxic preconditioning? and (2) does hypoxemia and hypercapnia during wakefulness in obesity hypoventilation syndrome (OHS) evoke a protective cardiovascular effect in contrast to patients with severe OSA who experience hypoxemia only during sleep?

Regarding the first question, we think the final pathway of the so-called ischemia preconditioning phenomenon is tissue hypoxia caused by reduction in blood flow, arterial hypoxemia, or both. Patients with OSA and OHS experience a reduction in blood flow after each obstructive event because of cyclic surges in sympathetic activity that lead to vasoconstriction. Furthermore, it is plausible that the degree of myocardial dysfunction is greater when tissue hypoxia is caused by vasoconstriction combined with arterial hypoxemia than by arterial hypoxemia alone.

Ischemic preconditioning seems to occur more readily with sustained hypoxemia than with intermittent hypoxemia. Patients with OHS are exposed to both types of hypoxemia; therefore, it is likely that there is an additive effect. In fact in our study, the prevalence of cardiovascular morbidity was lowest in patients with OHS who also had the most severe form of OSA. This finding supports the notion that sustained and intermittent hypoxemia may result in a more powerful angiogenic stimulation than either one alone. Clearly these findings are hypothesis generating, and further research is necessary. In summary, we do not think sustained hypoxemia is the only reason for the protective cardiovascular effect we observed in our patients with OHS and the most severe form of OSA, but rather it is a combination of cumulative exposure to significant hypoxemia during wakefulness due to hypoventilation plus intermittent hypoxemia during sleep due to very severe OSA. It remains unclear whether hypercapnia modulates the effect of hypoxemia, since experiments involving hypoxic preconditioning did not include exposure to hypercapnia.

References

Masa J.F. .Corral J. .Romero A. .et al Protective cardiovascular effect of sleep apnea severity in obesity hypoventilation syndrome. Chest. 2016;150:68-79 [PubMed]journal. [CrossRef] [PubMed]
 
Shizukuda Y. .Mallet R.T. .Lee S.C. .Downey H.F. . Hypoxic preconditioning of ischaemic canine myocardium. Cardiovasc Res. 1992;26:534-542 [PubMed]journal. [CrossRef] [PubMed]
 
Ryan S. .Taylor C.T. .McNicholas W.T. . Selective activation of inflammatory pathways by intermittent hypoxia in obstructive sleep apnea syndrome. Circulation. 2005;112:2660-2667 [PubMed]journal. [CrossRef] [PubMed]
 

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References

Masa J.F. .Corral J. .Romero A. .et al Protective cardiovascular effect of sleep apnea severity in obesity hypoventilation syndrome. Chest. 2016;150:68-79 [PubMed]journal. [CrossRef] [PubMed]
 
Shizukuda Y. .Mallet R.T. .Lee S.C. .Downey H.F. . Hypoxic preconditioning of ischaemic canine myocardium. Cardiovasc Res. 1992;26:534-542 [PubMed]journal. [CrossRef] [PubMed]
 
Ryan S. .Taylor C.T. .McNicholas W.T. . Selective activation of inflammatory pathways by intermittent hypoxia in obstructive sleep apnea syndrome. Circulation. 2005;112:2660-2667 [PubMed]journal. [CrossRef] [PubMed]
 
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