TY - JOUR
T1 - Early Human Pathophysiological Responses to Exertional Hypobaric Decompression Stress
AU - Connolly, Desmond M
AU - Madden, Leigh A
AU - Edwards, Victoria C
AU - D'Oyly, Timothy J
AU - Harridge, Stephen D R
AU - Smith, Thomas G
AU - Lee, Vivienne M
N1 - Funding Information:
The underpinning study design, methodology, and non-biomarker outcomes are described in detail elsewhere.6 Relevant details are summarized here for convenience. The study adhered to the principles of the Declaration of Helsinki. The research was funded by the UK Ministry of Defence (MOD) and the experimental protocol was approved in advance by the MOD Research Ethics Committee, an independent body constituted and operated in accordance with national and international guidelines.
Funding Information:
This work was funded by the UK Ministry of Defence under the Aircrew Systems Research project. The authors acknowledge with gratitude the support received from the Defence Science and Technology Laboratory (DSTL), especially the assistance provided by the staff of the Clinical Laboratory at DSTL Porton Down. We also wish to thank the many volunteers, investigators, colleagues, and advisers who have contributed to ensuring the successful outcome from these experiments at a particularly difficult time, due to the pandemic. Their support has been given freely, often at considerable personal inconvenience, and has proven invaluable
Publisher Copyright:
© copyright by the Aerospace Medical Association, Alexandria, VA.
PY - 2023/10/1
Y1 - 2023/10/1
N2 - INTRODUCTION: Consistent blood biomarkers of hypobaric (altitude) decompression stress remain elusive. Recent laboratory investigation of decompression sickness risk at 25,000 ft (7620 m) enabled evaluation of early pathophysiological responses to exertional decompression stress. METHODS: I n this study, 15 healthy men, aged 20–50 yr, undertook 2 consecutive (same-day) ascents to 25,000 ft (7620 m) for 60 and 90 min, breathing 100% oxygen, each following 1 h of prior denitrogenation. Venous blood was sampled at baseline (T0), immediately after the second ascent (T8), and next morning (T24). Analyses encompassed whole blood hematology, endothelial microparticles, and soluble markers of cytokine response, endothelial function, inflammation, coagulopathy, oxidative stress, and brain insult, plus cortisol and creatine kinase. RESULTS: Acute hematological effects on neutrophils (mean 72% increase), eosinophils (40% decrease), monocytes (37% increase), and platelets (7% increase) normalized by T24. Consistent elevation (mean five-fold) of the cytokine interleukin-6 (IL-6) at T8 was proinflammatory and associated with venous gas emboli (microbubble) load. Levels of C-reactive protein and complement peptide C5a were persistently elevated at T24, the former by 100% over baseline. Additionally, glial fibrillary acidic protein, a sensitive marker of traumatic brain injury, increased by a mean 10% at T24. CONCLUSIONS: This complex composite environmental stress, comprising the triad of hyperoxia, decompression, and moderate exertion at altitude, provoked pathophysiological changes consistent with an IL-6 cytokine-mediated inflammatory response. Multiple persistent biomarker disturbances at T24 imply incomplete recovery the day after exposure. The elevation of glial fibrillary acidic protein similarly implies incomplete resolution following recent neurological insult.
AB - INTRODUCTION: Consistent blood biomarkers of hypobaric (altitude) decompression stress remain elusive. Recent laboratory investigation of decompression sickness risk at 25,000 ft (7620 m) enabled evaluation of early pathophysiological responses to exertional decompression stress. METHODS: I n this study, 15 healthy men, aged 20–50 yr, undertook 2 consecutive (same-day) ascents to 25,000 ft (7620 m) for 60 and 90 min, breathing 100% oxygen, each following 1 h of prior denitrogenation. Venous blood was sampled at baseline (T0), immediately after the second ascent (T8), and next morning (T24). Analyses encompassed whole blood hematology, endothelial microparticles, and soluble markers of cytokine response, endothelial function, inflammation, coagulopathy, oxidative stress, and brain insult, plus cortisol and creatine kinase. RESULTS: Acute hematological effects on neutrophils (mean 72% increase), eosinophils (40% decrease), monocytes (37% increase), and platelets (7% increase) normalized by T24. Consistent elevation (mean five-fold) of the cytokine interleukin-6 (IL-6) at T8 was proinflammatory and associated with venous gas emboli (microbubble) load. Levels of C-reactive protein and complement peptide C5a were persistently elevated at T24, the former by 100% over baseline. Additionally, glial fibrillary acidic protein, a sensitive marker of traumatic brain injury, increased by a mean 10% at T24. CONCLUSIONS: This complex composite environmental stress, comprising the triad of hyperoxia, decompression, and moderate exertion at altitude, provoked pathophysiological changes consistent with an IL-6 cytokine-mediated inflammatory response. Multiple persistent biomarker disturbances at T24 imply incomplete recovery the day after exposure. The elevation of glial fibrillary acidic protein similarly implies incomplete resolution following recent neurological insult.
KW - Male
KW - Humans
KW - Glial Fibrillary Acidic Protein
KW - Interleukin-6
KW - Eosinophils
KW - Cytokines
KW - Decompression
UR - http://www.scopus.com/inward/record.url?scp=85171901735&partnerID=8YFLogxK
U2 - 10.3357/AMHP.6247.2023
DO - 10.3357/AMHP.6247.2023
M3 - Article
C2 - 37726900
SN - 2375-6314
VL - 94
SP - 738
EP - 749
JO - Aerospace medicine and human performance
JF - Aerospace medicine and human performance
IS - 10
ER -