Abstract
Background Haemorheological alterations are reported in obstructive sleep apnoea (OSA) and reversed with continuous positive airway pressure (CPAP), observations potentially explained by intermittent hypoxia (IH)-induced oxidative stress. Our objective was to investigate whether IH causes haemorheological alterations via oxidative stress.
Methods Wistar rats were exposed to normoxia (n=7) or IH (n=8) for 14 days. 23 moderate-to-severe OSA patients were assessed at three time-points: baseline, after randomisation to either 2 weeks of nocturnal oxygen (n=13) or no treatment (n=10) and after 1 month of CPAP treatment (n=17). Furthermore, an OSA-free control group (n=13) was assessed at baseline and after time-matched follow-up. We measured haemorheological parameters (haematocrit, blood viscosity, plasma viscosity (rats only), erythrocyte aggregation and deformability (humans only)) and redox balance (superoxide dismutase (SOD), glutathione peroxidase, protein oxidation (advanced oxidation protein products (AOPPs)) and lipid peroxidation (malondialdehyde)). We also tested the haemorheological sensitivity of erythrocytes to reactive oxygen species (ROS) in our human participants using the oxidant t-butyl hydroperoxide (TBHP).
Results In rats, IH increased blood viscosity by increasing haematocrit without altering the haemorheological properties of erythrocytes. IH also reduced SOD activity and increased AOPPs. In humans, baseline haemorheological properties were similar between patients and control participants, and properties were unaltered following oxygen and CPAP, except erythrocyte deformability was reduced following oxygen therapy. Redox balance was comparable between patients and control participants. At baseline, TBHP induced a greater reduction of erythrocyte deformability in patients while CPAP reduced TBHP-induced increase in aggregation strength.
Conclusions IH and OSA per se do not cause haemorheological alterations despite the presence of oxidative stress or higher sensitivity to ROS, respectively.
Abstract
Obstructive sleep apnoea and/or intermittent hypoxia per se are not significantly implicated in haemorheological disturbances https://bit.ly/3seciGd
Footnotes
This article has supplementary material available from erj.ersjournals.com
This article has an editorial commentary: https://doi.org/10.1183/13993003.01169-2021
Author contributions: The work outlined in this manuscript was led by a multigroup collaboration of senior team members including P.J. Hanly (OSA), V. Pialoux (oxidative stress), E. Belaidi and J-L. Pépin (IH in rodents), and S. Verges and M.J. Poulin (human integrative physiology and IH). X. Waltz, A.E. Beaudin, P.J. Hanly and M.J. Poulin conceived the experimental design of studies conducted in patients with OSA. E. Belaidi, X. Waltz, J-L. Pépin and S. Verges conceived the experimental design of studies conducted in rodents. Primary supervision for X. Waltz was provided by P.J. Hanly and M.J. Poulin (Calgary) and S. Verges (Grenoble), and primary supervision for A.E. Beaudin was provided by P.J. Hanly and M.J. Poulin. The experiments in patients with OSA were performed by A.E. Beaudin, J. Raneri and X. Waltz. The experiments in rodents were performed by X. Waltz and E. Belaidi. All co-authors contributed to the interpretation of the data. X. Waltz wrote the first draft of the manuscript and other co-authors edited the manuscript.
Conflict of interest: X. Waltz has nothing to disclose.
Conflict of interest: A.E. Beaudin reports other (scholarships) from the Canadian Institutes of Health Research – Heart and Stroke Foundation of Canada (HSFC), Alberta Innovates – Health Solutions (AIHS), and University of Calgary, during the conduct of the study.
Conflict of interest: E. Belaidi has nothing to disclose.
Conflict of interest: J. Raneri has nothing to disclose.
Conflict of interest: J-L. Pépin reports grants and other (research funds) from Air Liquide Foundation, grants, personal fees and other (research funds) from Agiradom, AstraZeneca, Philips and ResMed, grants and personal fees from Fisher and Paykel, Mutualia and Vitalaire, personal fees from Boehringer Ingelheim, Jazz Pharmaceutical, Night Balance and Sefam, outside the submitted work.
Conflict of interest: V. Pialoux has nothing to disclose.
Conflict of interest: P.J. Hanly has nothing to disclose.
Conflict of interest: S. Verges has nothing to disclose.
Conflict of interest: M.J. Poulin has nothing to disclose.
Support statement: X. Waltz received support from a Harley N. Hotchkiss Postdoctoral Fellowship (Hotchkiss Brain Institute (HBI)), Alberta Innovates – Health Solutions (AIHS) Postgraduate Fellowship programme, Canadian Institutes of Health Research (CIHR) Postdoctoral Fellowship, European Respiratory Society (ERS) Long-term Fellowship and “Fonds de dotation pour la Recherche en Santé Respiratoire (FRSR)”. A.E. Beaudin was supported by an AIHS Doctoral Fellowship, CIHR – Heart and Stroke Foundation of Canada (HSFC) Focus on Stroke Doctoral Fellowship, William H. Davies Medical Research Scholarship (University of Calgary), and Osten-Victor Graduate Scholarship in Cardiology (University of Calgary). Funding for the human part of the present project was provided by CIHR (PI M.J. Poulin, co-applicant P.J. Hanly) and BRAIN CREATE (an interdisciplinary training programme) funded by the Natural Sciences and Engineering Research Council of Canada (PI M.J. Poulin). Funding for the animal part of the present project was provided by “le fond de dotation AGIR pour les maladies chroniques” (E. Belaidi, S. Verges and J-L. Pépin). The LORRCA MaxSis (haemorheological measurements) was purchased with the HBI donor fund (University of Calgary). M.J. Poulin holds the Brenda Strafford Foundation Chair in Alzheimer Research. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received February 4, 2021.
- Accepted April 8, 2021.
- Copyright ©The authors 2021. For reproduction rights and permissions contact permissions{at}ersnet.org
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