European Journal of Applied Physiology

, Volume 117, Issue 2, pp 335–344 | Cite as

Venous gas emboli are involved in post-dive macro, but not microvascular dysfunction

  • Kate Lambrechts
  • Costantino Balestra
  • Michaël Theron
  • Anne Henckes
  • Hubert Galinat
  • Fanny Mignant
  • Marc Belhomme
  • Jean-Michel Pontier
  • François GuerreroEmail author
Original Article



Previous studies have shown vascular dysfunction of main conductance arteries and microvessels after diving. We aim to evaluate the impact of bubble formation on vascular function and haemostasis. To achieve this, we used a vibration preconditioning to influence bubble levels without changing any other parameters linked to the dive.


Twentty-six divers were randomly assigned to one of three groups: (1) the “vibrations–dive” group (VD; n = 9) was exposed to a whole-body vibration session 30 min prior the dive; (2) the “diving” group (D; n = 9) served as a control for the effect of the diving protocol; (3) The “vibration” protocol (V; n = 8) allowed us to assess the effect of vibrations without diving. Macro- and microvascular function was assessed for each subject before and after the dive, subsequently. Bubble grades were monitored with Doppler according to the Spencer grading system. Blood was taken before and after the protocol to assess any change of platelets or endothelial function.


Bubble formation was lower in the VD than the diving group. The other measured parameters remained unchanged after the “vibration” protocol alone. Diving alone induced macrovascular dysfunction, and increased PMP and thrombin generation. Those parameters were no longer changed in the VD group. Conversely, a microvascular dysfunction persists despite a significant decrease of circulating bubbles.


Finally, the results of this study suggest that macro- but not microvascular impairment results at least partly from bubbles, possibly related to platelet activation and generation of pro-coagulant microparticles.


SCUBA Decompression Brachial artery Cutaneous microcirculation Vibration preconditionning Platelets 



This work is part of the PHYPODE European network. This study was supported by the European Commission under the FP7-PEOPLE-2010-ITN program (Grant Agreement No. 264816).


  1. Baj Z, Olszański R, Majewska E, Konarski M (2000) The effect of air and nitrox divings on platelet activation tested by flow cytometry. Aviat Space Environ Med 71:925–928PubMedGoogle Scholar
  2. Balestra C, Theunissen S, Papadopoulou V et al (2016) Pre-dive whole-body vibration better reduces decompression-induced vascular gas emboli than oxygenation or a combination of both. Front Physiol. doi: 10.3389/fphys.2016.00586 PubMedPubMedCentralGoogle Scholar
  3. Berghoff M, Kathpal M, Kilo S et al (2002) Vascular and neural mechanisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation. J Appl Physiol 92:780–788. doi: 10.1152/japplphysiol.01167.2000 CrossRefPubMedGoogle Scholar
  4. Brubakk AO, Duplancic D, Valic Z et al (2005) A single air dive reduces arterial endothelial function in man: air dive and endothelial function. J Physiol 566:901–906. doi: 10.1113/jphysiol.2005.089862 CrossRefPubMedPubMedCentralGoogle Scholar
  5. Bryckaert M, Rosa J-P, Denis CV, Lenting PJ (2015) Of von Willebrand factor and platelets. Cell Mol Life Sci 72:307–326. doi: 10.1007/s00018-014-1743-8 CrossRefPubMedGoogle Scholar
  6. Celermajer DS, Sorensen KE, Gooch VM et al (1992) Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet Lond Engl 340:1111–1115.CrossRefGoogle Scholar
  7. Corretti MC, Anderson TJ, Benjamin EJ et al (2002) Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 39:257–265CrossRefPubMedGoogle Scholar
  8. Dujic Z, Palada I, Valic Z et al (2006) Exogenous nitric oxide and bubble formation in divers. Med Sci Sports Exerc 38:1432–1435. doi: 10.1249/01.mss.0000228936.78916.23 CrossRefPubMedGoogle Scholar
  9. Ersson A, Walles M, Ohlsson K, Ekholm A (2002) Chronic hyperbaric exposure activates proinflammatory mediators in humans. J Appl Physiol 92:2375–2380. doi: 10.1152/japplphysiol.00705.2001 CrossRefPubMedGoogle Scholar
  10. Fok H, Jiang B, Chowienczyk P, Clapp B (2015) Microbubbles shunting via a patent foramen ovale impair endothelial function. JRSM Cardiovasc Dis. doi: 10.1177/2048004015601564 PubMedPubMedCentralGoogle Scholar
  11. Gempp E, Blatteau J-E (2010) Preconditioning methods and mechanisms for preventing the risk of decompression sickness in scuba divers: a review. Res Sports Med 18:205–218. doi: 10.1080/15438627.2010.490189 CrossRefPubMedGoogle Scholar
  12. Germonpré P, Balestra C (2017) Preconditioning to reduce decompression stress in Scuba divers. Aerosp Med Hum Perform 88:1–7Google Scholar
  13. Germonpré P, Pontier J-M, Gempp E et al (2009) Pre-dive vibration effect on bubble formation after a 30-m dive requiring a decompression stop. Aviat Space Environ Med 80:1044–1048CrossRefPubMedGoogle Scholar
  14. Kanaji S, Fahs SA, Shi Q et al (2012) Contribution of platelet vs. endothelial VWF to platelet adhesion and hemostasis: hemostatic effect of platelet VWF in murine VWD. J Thromb Haemost 10:1646–1652. doi: 10.1111/j.1538-7836.2012.04797.x CrossRefPubMedPubMedCentralGoogle Scholar
  15. Klinger AL, Pichette B, Sobolewski P, Eckmann DM (2011) Mechanotransductional basis of endothelial cell response to intravascular bubbles. Integr Biol 3:1033. doi: 10.1039/c1ib00017a CrossRefGoogle Scholar
  16. Lambrechts K, Pontier J-M, Balestra C et al (2013a) Effect of a single, open-sea, air scuba dive on human micro- and macrovascular function. Eur J Appl Physiol 113:2637–2645. doi: 10.1007/s00421-013-2676-x
  17. Lambrechts K, Pontier J-M, Balestra C et al (2013b) Effect of a single, open-sea, air scuba dive on human micro-and macrovascular function. Eur J Appl Physiol 113:2637–2645Google Scholar
  18. Lambrechts K, Pontier J-M, Mazur A et al (2013c) Effect of decompression-induced bubble formation on highly trained divers microvascular function. Physiol Rep. doi: 10.1002/phy2.142
  19. Lambrechts K, Pontier J-M, Mazur A et al (2015) Mechanism of action of antiplatelet drugs on decompression sickness in rats: a protective effect of anti-GPIIbIIIa therapy. J Appl Physiol 118:1234–1239. doi: 10.1152/japplphysiol.00125.2015 CrossRefPubMedGoogle Scholar
  20. Li Y, Li L, Dong F et al (2015) Plasma von Willebrand factor level is transiently elevated in a rat model of acute myocardial infarction. Exp Ther Med. doi: 10.3892/etm.2015.2721 Google Scholar
  21. Marinovic J, Ljubkovic M, Breskovic T et al (2012) Effects of successive air and nitrox dives on human vascular function. Eur J Appl Physiol 112:2131–2137. doi: 10.1007/s00421-011-2187-6 CrossRefPubMedGoogle Scholar
  22. Mazur A, Lambrechts K, Wang Q et al (2016) Influence of decompression sickness on vasocontraction of isolated rat vessels. J Appl Physiol 120:784–791. doi: 10.1152/japplphysiol.00139.2015 CrossRefPubMedGoogle Scholar
  23. Mheid IA, Corrigan F, Shirazi F et al (2014) Circadian variation in vascular function and regenerative capacity in healthy humans. J Am Heart Assoc 3:e000845–e000845. doi: 10.1161/JAHA.114.000845 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Nossum V, Hjelde A, Brubakk AO (2002) Small amounts of venous gas embolism cause delayed impairment of endothelial function and increase polymorphonuclear neutrophil infiltration. Eur J Appl Physiol 86:209–214CrossRefPubMedGoogle Scholar
  25. Obad A, Palada I, Valic Z et al (2007a) The effects of acute oral antioxidants on diving-induced alterations in human cardiovascular function: antioxidants and endothelium-dependent dilatation after field diving. J Physiol 578:859–870. doi: 10.1113/jphysiol.2006.122218
  26. Obad A, Valic Z, Palada I et al (2007b) Antioxidant pretreatment and reduced arterial endothelial dysfunction after diving. Aviat Space Environ Med 78:1114–1120Google Scholar
  27. Obad A, Marinovic J, Ljubkovic M et al (2010) Successive deep dives impair endothelial function and enhance oxidative stress in man: deep trimix dives impair endothelial function. Clin Physiol Funct Imaging 30:432–438. doi: 10.1111/j.1475-097X.2010.00962.x CrossRefPubMedGoogle Scholar
  28. Papadopoulou V, Tang M-X, Balestra C et al (2014) Circulatory bubble dynamics: from physical to biological aspects. Adv Colloid Interface Sci 206:239–249. doi: 10.1016/j.cis.2014.01.017 CrossRefPubMedGoogle Scholar
  29. Pontier J-M, Blatteau J-E, Vallée N (2008a) Blood platelet count and severity of decompression sickness in rats after a provocative dive. Aviat Space Environ Med 79:761–764Google Scholar
  30. Pontier J-M, Jimenez C, Blatteau J-E (2008b) Blood platelet count and bubble formation after a dive to 30 msw for 30 min. Aviat Space Environ Med 79:1096–1099Google Scholar
  31. Pontier J-M, Vallee N, Bourdon L (2009) Bubble-induced platelet aggregation in a rat model of decompression sickness. J Appl Physiol 107:1825–1829. doi: 10.1152/japplphysiol.91644.2008 CrossRefPubMedGoogle Scholar
  32. Pontier J-M, Gempp E, Ignatescu M (2012) Blood platelet-derived microparticles release and bubble formation after an open-sea air dive. Appl Physiol Nutr Metab 37:888–892. doi: 10.1139/h2012-067 CrossRefPubMedGoogle Scholar
  33. Pyke KE, Tschakovsky ME (2005) The relationship between shear stress and flow-mediated dilatation: implications for the assessment of endothelial function: The shear stress stimulus-flow-mediated dilatation relationship. J Physiol 568:357–369. doi: 10.1113/jphysiol.2005.089755 CrossRefPubMedPubMedCentralGoogle Scholar
  34. Roustit M, Cracowski J-L (2012) Non-invasive assessment of skin microvascular function in humans: an insight into methods: methods to assess skin microvascular function. Microcirculation 19:47–64. doi: 10.1111/j.1549-8719.2011.00129.x CrossRefPubMedGoogle Scholar
  35. Sobolewski P, Kandel J, Klinger AL, Eckmann DM (2011) Air bubble contact with endothelial cells in vitro induces calcium influx and IP3-dependent release of calcium stores. AJP Cell Physiol 301:C679–C686. doi: 10.1152/ajpcell.00046.2011 CrossRefGoogle Scholar
  36. Theunissen S, Guerrero F, Sponsiello N et al (2013a) Nitric oxide-related endothelial changes in breath-hold and scuba divers. Undersea Hyperb Med J Undersea Hyperb Med Soc Inc 40:135–144Google Scholar
  37. Theunissen S, Schumacker J, Guerrero F et al (2013b) Dark chocolate reduces endothelial dysfunction after successive breath-hold dives in cool water. Eur J Appl Physiol 113:2967–2975. doi: 10.1007/s00421-013-2732-6
  38. Theunissen S, Sponsiello N, Rozloznik M et al (2013c) Oxidative stress in breath-hold divers after repetitive dives. Diving Hyperb Med 43:63–66Google Scholar
  39. Theunissen S, Balestra C, Boutros A et al (2015) The effect of pre-dive ingestion of dark chocolate on endothelial function after a scuba dive. Diving Hyperb Med 45:4–9PubMedGoogle Scholar
  40. Thom SR, Yang M, Bhopale VM et al (2011) Microparticles initiate decompression-induced neutrophil activation and subsequent vascular injuries. J Appl Physiol 110:340–351. doi: 10.1152/japplphysiol.00811.2010 CrossRefPubMedGoogle Scholar
  41. Thom SR, Yang M, Bhopale VM et al (2013) Intramicroparticle nitrogen dioxide is a bubble nucleation site leading to decompression-induced neutrophil activation and vascular injury. J Appl Physiol 114:550–558. doi: 10.1152/japplphysiol.01386.2012 CrossRefPubMedGoogle Scholar
  42. Thom SR, Bennett M, Banham ND et al (2015) Association of microparticles and neutrophil activation with decompression sickness. J Appl Physiol 119:427–434. doi: 10.1152/japplphysiol.00380.2015 CrossRefPubMedGoogle Scholar
  43. Turner J, Belch JJF, Khan F (2008) Current concepts in assessment of microvascular endothelial function using laser doppler imaging and iontophoresis. Trends Cardiovasc Med 18:109–116. doi: 10.1016/j.tcm.2008.02.001 CrossRefPubMedGoogle Scholar
  44. van Hinsbergh VWM (2012) Endothelium—role in regulation of coagulation and inflammation. Semin Immunopathol 34:93–106. doi: 10.1007/s00281-011-0285-5 CrossRefPubMedGoogle Scholar
  45. Wang Q, Belhomme M, Guerrero F et al (2013) Diving under a microscope—a new simple and versatile in vitro diving device for fluorescence and confocal microscopy allowing the controls of hydrostatic pressure, gas pressures, and kinetics of gas saturation. Microsc Microanal 19:608–616. doi: 10.1017/S1431927613000378 CrossRefPubMedGoogle Scholar
  46. Wang Q, Guerrero F, Mazur A et al (2015) Reactive oxygen species, mitochondria, and endothelial cell death during in vitro simulated dives. Med Sci Sports Exerc 47:1362–1371. doi: 10.1249/MSS.0000000000000563 CrossRefPubMedGoogle Scholar
  47. Yang M, Barak OF, Dujic Z et al (2015a) Ascorbic acid supplementation diminishes microparticle elevations and neutrophil activation following SCUBA diving. Am J Physiol Regul Integr Comp Physiol 309:R338–R344. doi: 10.1152/ajpregu.00155.2015
  48. Yang M, Bhopale VM, Thom SR (2015b) Separating the roles of nitrogen and oxygen in high pressure-induced blood-borne microparticle elevations, neutrophil activation, and vascular injury in mice. J Appl Physiol 119:219–222. doi: 10.1152/japplphysiol.00384.2015

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Kate Lambrechts
    • 1
    • 2
  • Costantino Balestra
    • 3
  • Michaël Theron
    • 1
  • Anne Henckes
    • 4
  • Hubert Galinat
    • 5
  • Fanny Mignant
    • 5
  • Marc Belhomme
    • 1
  • Jean-Michel Pontier
    • 6
  • François Guerrero
    • 1
    Email author
  1. 1.ORPHY Laboratory, UBOBrestFrance
  2. 2.IRBA-ERRSO, Armed Forces Biomedical Research Institute-Resident Operational Subaquatic Research Team, ToulonToulonFrance
  3. 3.Environmental and Occupational Physiology Laboratory (ISEK)Haute Ecole Bruxelles-Brabant (HE2B)BrusselsBelgium
  4. 4.Hyperbaric Medicine UnitCHRU Cavale BlancheBrestFrance
  5. 5.Hematology LaboratoryCHRU Cavale BlancheBrestFrance
  6. 6.Hyperbaric Medicine and Diving Expertise Department, Military Teaching HospitalHIA Sainte AnneToulonFrance

Personalised recommendations