Severe hypoxaemic hypercapnia compounds cerebral oxidative–nitrosative stress during extreme apnoea: Implications for cerebral bioenergetic function

Author:

Bailey Damian M.1ORCID,Bain Anthony R.2ORCID,Hoiland Ryan L.34,Barak Otto F.56,Drvis Ivan7,Stacey Benjamin S.1ORCID,Iannetelli Angelo1,Davison Gareth W.8,Dahl Rasmus H.9ORCID,Berg Ronan M. G.110,MacLeod David B.11ORCID,Dujic Zeljko5,Ainslie Philip N.112ORCID

Affiliation:

1. Neurovascular Research Laboratory, Faculty of Life Sciences and Education University of South Wales Glamorgan UK

2. Department of Kinesiology, Faculty of Human Kinetics University of Windsor Windsor ON Canada

3. Department of Anaesthesiology, Pharmacology and Therapeutics, Vancouver General Hospital, West 12th Avenue University of British Columbia Vancouver BC Canada

4. Department of Cellular and Physiological Sciences, Faculty of Medicine University of British Columbia Vancouver BC Canada

5. Department of Integrative Physiology, School of Medicine University of Split Split Croatia

6. Department of Sports Medicine, Faculty of Medicine University of Novi Sad Novi Sad Serbia

7. School of Kinesiology University of Zagreb Zagreb Croatia

8. Department of Exercise Biochemistry and Physiology, Sport and Exercise Science Research Institute Ulster University Belfast, United Kingdom of Great Britain and Northern Ireland Ulster UK

9. Department of Radiology University Hospital Rigshospitalet Copenhagen Denmark

10. Department of Biomedical Sciences University of Copenhagen Denmark

11. Department of Anesthesiology Duke University Medical Center Durham NC USA

12. School of Health and Exercise Sciences, Faculty of Health and Social Development, Center for Heart Lung and Vascular Health University of British Columbia Kelowna BC Canada

Abstract

AbstractWe examined the extent to which apnoea‐induced extremes of oxygen demand/carbon dioxide production impact redox regulation of cerebral bioenergetic function. Ten ultra‐elite apnoeists (six men and four women) performed two maximal dry apnoeas preceded by normoxic normoventilation, resulting in severe end‐apnoea hypoxaemic hypercapnia, and hyperoxic hyperventilation designed to ablate hypoxaemia, resulting in hyperoxaemic hypercapnia. Transcerebral exchange of ascorbate radicals (by electron paramagnetic resonance spectroscopy) and nitric oxide metabolites (by tri‐iodide chemiluminescence) were calculated as the product of global cerebral blood flow (by duplex ultrasound) and radial arterial (a) to internal jugular venous (v) concentration gradients. Apnoea duration increased from 306 ± 62 s during hypoxaemic hypercapnia to 959 ± 201 s in hyperoxaemic hypercapnia (P ≤ 0.001). Apnoea generally increased global cerebral blood flow (all P ≤ 0.001) but was insufficient to prevent a reduction in the cerebral metabolic rates of oxygen and glucose (P = 0.015–0.044). This was associated with a general net cerebral output (v > a) of ascorbate radicals that was greater in hypoxaemic hypercapnia (P = 0.046 vs. hyperoxaemic hypercapnia) and coincided with a selective suppression in plasma nitrite uptake (a > v) and global cerebral blood flow (P = 0.034 to <0.001 vs. hyperoxaemic hypercapnia), implying reduced consumption and delivery of nitric oxide consistent with elevated cerebral oxidative–nitrosative stress. In contrast, we failed to observe equidirectional gradients consistent with S‐nitrosohaemoglobin consumption and plasma S‐nitrosothiol delivery during apnoea (all P ≥ 0.05). Collectively, these findings highlight a key catalytic role for hypoxaemic hypercapnia in cerebral oxidative–nitrosative stress. imageKey points Local sampling of blood across the cerebral circulation in ultra‐elite apnoeists determined the extent to which severe end‐apnoea hypoxaemic hypercapnia (prior normoxic normoventilation) and hyperoxaemic hypercapnia (prior hyperoxic hyperventilation) impact free radical‐mediated nitric oxide bioavailability and global cerebral bioenergetic function. Apnoea generally increased the net cerebral output of free radicals and suppressed plasma nitrite consumption, thereby reducing delivery of nitric oxide consistent with elevated oxidative–nitrosative stress. The apnoea‐induced elevation in global cerebral blood flow was insufficient to prevent a reduction in the cerebral metabolic rates of oxygen and glucose. Cerebral oxidative–nitrosative stress was greater during hypoxaemic hypercapnia compared with hyperoxaemic hypercapnia and coincided with a lower apnoea‐induced elevation in global cerebral blood flow, highlighting a key catalytic role for hypoxaemia. This applied model of voluntary human asphyxia might have broader implications for the management and treatment of neurological diseases characterized by extremes of oxygen demand and carbon dioxide production.

Funder

Natural Sciences and Engineering Research Council of Canada

Hrvatska Zaklada za Znanost

Publisher

Wiley

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3