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



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.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  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 71:925–928

    CAS  PubMed  Google 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

    PubMed  PubMed Central  Google 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

    CAS  Article  PubMed  Google 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

    CAS  Article  PubMed  PubMed Central  Google 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

    CAS  Article  PubMed  Google 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.

    CAS  Article  Google 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 39:257–265

    Article  PubMed  Google 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

    CAS  Article  PubMed  Google 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

    CAS  Article  PubMed  Google 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

    PubMed  PubMed Central  Google 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

    Article  PubMed  Google Scholar 

  12. Germonpré P, Balestra C (2017) Preconditioning to reduce decompression stress in Scuba divers. Aerosp Med Hum Perform 88:1–7

    Google 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 80:1044–1048

    Article  PubMed  Google 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

    CAS  Article  PubMed  PubMed Central  Google 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

    CAS  Article  Google 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 113:2637–2645

  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

    CAS  Article  PubMed  Google 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

    CAS  Article  PubMed  Google 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

    Article  PubMed  Google 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

    Article  PubMed  PubMed Central  Google 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 86:209–214

    CAS  Article  PubMed  Google 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 78:1114–1120

  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

    Article  PubMed  Google 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

    CAS  Article  PubMed  Google 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 79:761–764

  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 79:1096–1099

  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

    Article  PubMed  Google 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

    CAS  Article  PubMed  Google 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

    CAS  Article  PubMed  PubMed Central  Google 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

    Article  PubMed  Google 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

    CAS  Article  Google 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 40:135–144

  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 43:63–66

  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 45:4–9

    PubMed  Google 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

    CAS  Article  PubMed  Google 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

    CAS  Article  PubMed  Google 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

    CAS  Article  PubMed  Google 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

    CAS  Article  PubMed  Google 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

    Article  PubMed  Google 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

    CAS  Article  PubMed  Google 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

    CAS  Article  PubMed  Google 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

Download references


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).

Author information



Corresponding author

Correspondence to François Guerrero.

Additional information

Communicated by Guido Ferretti.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Lambrechts, K., Balestra, C., Theron, M. et al. Venous gas emboli are involved in post-dive macro, but not microvascular dysfunction. Eur J Appl Physiol 117, 335–344 (2017).

Download citation


  • Decompression
  • Brachial artery
  • Cutaneous microcirculation
  • Vibration preconditionning
  • Platelets