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Increase of pulmonary arterial pressure in subjects with venous gas emboli after uncomplicated recreational SCUBA diving

Open ArchivePublished:February 01, 2013DOI:https://doi.org/10.1016/j.rmed.2013.01.002

      Summary

      The presence of circulating gas bubbles has been repeatedly reported after uncomplicated SCUBA dives. The clinical and pathophysiological relevance of this phenomenon is still under debate but some experimental data suggest that silent bubbles may have a damaging potential on pulmonary endothelial cells. The aim of the present study was to evaluate the possible hemodynamic effect on pulmonary circulation of post-dive circulating gas bubbles. To this aim, 16 experienced divers were studied by Doppler-echocardiography in basal conditions and 2.0 ± 0.15 h after an uncomplicated, unrestricted recreational SCUBA dive.
      At the post-dive examination, circulating bubbles were present in 10/16 subjects (62.5%). Divers with circulating bubbles showed a significant post-dive increase of pulmonary systolic arterial pressure (evaluated by the maximal velocity of the physiological tricuspid regurgitation; P < 0.01)) and right ventricular internal dimension (P < 0.05). Divers without circulating bubbles showed no significant change in cardiac anatomy and pulmonary arterial pressure. Both groups showed a significant post-dive decrease of transmitral E/A ratio (index of left ventricular diastolic function: subjects with bubbles P < 0.01; subjects without bubbles P < 0.05).
      These results seem to indicate that circulating gas bubbles may lead to a hemodynamically relevant increase of pulmonary arterial pressure, able to induce an acute right ventricular dilation. Post-dive diastolic function changes, observed in both groups, may be explained by a preload reduction due to immersion natriuresis.
      The results of the present study add some evidence that post-dive circulating bubbles, although symptomless, have an easily detectable pathogenetic potential, inducing unfavorable hemodynamic changes in the lesser circulation.

      Keywords

      Introduction

      In recent years SCUBA diving has become a widely diffused recreational sport activity practiced all over the world. The risk of decompression illness in subjects following validated decompression procedures is reported to be low.

      Shields TG, Lee WB. The incidence of decompression sickness arising from commercial offshore air diving operations in the UK sector of North Sea during 1982–83. Robert Gordon's Institute of Technology and Grampian Health Board Report.

      Nevertheless, the presence of clinically silent circulating gas bubbles in venous circulation has been repeatedly reported in a significant number of subjects after uncomplicated SCUBA diving.
      • Spencer M.P.
      • Clarke H.F.
      Precordial monitoring of pulmonary gas embolism and decompression bubbles.
      • Marabotti C.
      • Chiesa F.
      • Scalzini A.
      • Antonelli F.
      • Lari R.
      • Franchini C.
      • et al.
      Cardiac and humoral changes induced by recreational SCUBA diving.
      Even if some recent decompression tables include information about the ultrasound evidence of circulating bubbles for the different dive profiles,
      • Spencer M.P.
      Decompression limits for compressed air determined by ultrasonically detected blood bubbles.
      the pathophysiological relevance of this finding is still under debate. A previous study of our group reported, in divers with circulating gas bubbles, right ventricular dilation, signs of pulmonary endothelial damage and impairment of left ventricular diastolic function, but the possible effects of silent bubbles on pulmonary hemodynamics was not investigated. Later papers addressing this matter showed conflicting results. In one case, pulmonary arterial blood pressure was reported to increase after a single open-sea dive to 30 m depth.
      • Dujic Z.
      • Obad A.
      • Palada I.
      • Valic Z.
      • Brubakk A.O.
      A single open sea air dive increases pulmonary artery pressure and reduces right ventricular function in professional divers.
      Conversely, Diesel and co-workers,
      • Diesel D.A.
      • Ryles M.T.
      • Pilmanis A.A.
      • Balldin U.I.
      Non-invasive measurement of pulmonary artery pressure in humans with simulated altitude-induced venous gas emboli.
      evaluating pulmonary hemodynamics in subjects undergoing hypobaric exposition (to a simulated altitude of more than 7000 m), failed to demonstrate significant changes in pulmonary arterial pressure in spite of high-grade venous gas emboli and high incidence of decompression sickness (37%). Both studies evaluated a population of professionals and were therefore hardly representative of the variegated people usually devoted to recreational diving.
      The aim of this study was to evaluate the possible effects of post-dive circulating silent bubbles on pulmonary arterial pressure and on cardiac function, in healthy subjects undergoing recreational SCUBA diving.

      Subjects and methods

      Sixteen experienced divers (14 male, 2 female; age 37 ± 12, range 20–61 years; BMI 24.8 ± 1.3 kg/sqm) underwent a Doppler-echocardiographic examination in basal conditions and 2.0 ± 0.15 h after a recreational SCUBA dive. All subjects were non-smokers and no one had history, clinical or instrumental (blood pressure measurement, resting ECG, Doppler-echocardiography) evidence of arterial hypertension, cardiac or pulmonary disease. No subject was aware of having patent foramen ovale; a screening for patent foramen ovale was not performed since its possible presence would not have affected the results of the study. The study was performed in mid-summer, a period during which all subjects regularly dived 2-to-3 times a week. To avoid interference with previous diving activity, divers were asked not to dive in the three days preceding the study. Doppler echocardiography was performed by a commercially available instrument (Sequoia C256; Acuson Corp., Mountain View; CA – USA). Echocardiographic parameters were obtained according to validated procedures.
      • Sahn D.J.
      • DeMaria A.
      • Kisslo J.
      • Weyman A.
      The Committee on M-mode Standardization of the American Society of Echocardiography
      Recommendations regard quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements.
      • Lang R.M.
      • Bierig M.
      • Devereux R.B.
      • Flachskampf F.A.
      • Foster E.
      • Pellikka P.A.
      • et al.
      Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology.
      Right ventricular diastolic dimension was obtained from an apical four-chamber view. From a parasternal 2D-oriented m-Mode tracing, left ventricular end-diastolic (EDD) and end-systolic (ESD) diameter were measured. Left ventricular fractional shortening, assumed as systolic function index, was calculated as 100*(EDD-ESD)*EDD−1
      Early (E) and late (A) peak velocities of diastolic ventricular filling flows, their ratio (E/A) and the deceleration time of E peak were obtained by pulsed-wave Doppler evaluation of both mitral and tricuspid diastolic flows.
      Pulmonary systolic arterial pressure was evaluated by the maximal velocity of the physiological tricuspid regurgitation (present in all subjects of this series).
      • Hatle L.
      • Angelsen B.,A.J.
      • Tromsdal A.
      Noninvasive estimation of pulmonary artery systolic pressure with Doppler ultrasound.
      To evaluate post-dive circulating bubbles, 20 s loops were recorded of the following echocardiographic views: apical four-chamber (to evaluate right ventricle and right atrium), heart basis short-axis (to evaluate right atrium, right ventricular outflow tract and main pulmonary artery), inferior vena cava and right atrium subcostal scan. A visual search for circulating bubbles was made off-line on recorded loops; bubble grading was performed according to previously validated scoring system, ranging from grade 0 (no observable bubbles) to grade 5 (“white-out”, single bubbles cannot be discriminated).
      • Eftedal O.
      • Brubakk A.O.
      Agreement between trained and untrained observers in grading intravascular bubble signals in ultrasonic images.
      Systemic blood pressure and heart rate were measured just before the two Doppler-echocardiographic examinations.
      All dives were performed within the no-decompression limits of a commercially available dive computer (Solution-Alpha; Suunto; Finland). Maximum depth and dive duration were (mean ± SD) 31.4 ± 3.7 m and 31.1 ± 7.1 min, respectively.
      Student's t-test for paired data was used to compare pre and post-dive data. Student's t-test for unpaired data was used to compare subjects with and without post-dive silent bubbles. A probability lower than 5% was assumed as threshold to reject the null hypothesis.
      The local University-Hospital Ethic Committee approved the study protocol. All participants received information about the aims and procedures of the study and gave their written consent.

      Results

      Prevalence of gas bubbles

      Circulating gas bubbles were observed, at the post-dive echocardiographic examination, in the right cardiac chambers of 10/16 subjects (62.5%). Although divers followed similar dive profiles, a wide variability in the number of bubbles was observed: bubble grade ranged from 1 to 4 (3 subjects grade 1; 2 subjects grade 2; 4 subjects grade 3; 1 subject grade 4). No subjects had bubbles in left heart chambers. Due to the low number of subjects in the different bubble grade classes, analysis was performed by considering subjects with post-dive bubble as a whole group.

      Demographic and basal ultrasonographic data in subjects with and without circulating bubbles

      The group with post-dive circulating bubbles had an age somewhat (even if not significantly) higher than subjects without bubbles (45.4 ± 9.9 vs. 34.0 ± 13.6 years; P = 0.06). The same group showed, at pre-dive evaluation, a significantly higher diastolic right ventricular internal dimensions (38.6 ± 3.4 vs. 33.7 ± 3.4 mm; P < 0.05) (Fig. 1). No significant differences were seen between groups for the others anatomical and functional parameters.
      Figure thumbnail gr1
      Figure 1Right ventricular internal dimensions (RVID) in the two groups of divers before and after diving. Solid squares: Divers with venous gas emboli; open squares: Divers without venous gas emboli. Larger squares indicate mean (±standard deviation).

      Post-dive cardiac changes in subjects with and without circulating bubbles

      In the group with post-dive bubbles, diving induced a significant increase of both systolic pulmonary arterial pressure (+18%, P < 0.01; Fig. 2) and right ventricular internal dimensions (+8%, P < 0.05; Fig. 1). In the same group, a significant post-dive decrease of left ventricular E/A ratio was observed (−25%, P < 0.01; Fig. 3). No significant change was seen for heart rate, systemic arterial pressure, left ventricular anatomic and systolic function indices, right ventricular diastolic function indices.
      Figure thumbnail gr2
      Figure 2Systolic pulmonary arterial pressure (S PAP) in the two groups of divers before and after diving. Solid squares: Divers with venous gas emboli; open squares: Divers without venous gas emboli. Larger squares indicate mean (±standard deviation).
      Figure thumbnail gr3
      Figure 3Left ventricular E/A ratio (LV E/A) in the two groups of divers before and after diving. Solid squares: Divers with venous gas emboli; open squares: Divers without venous gas emboli. Larger squares indicate mean (±standard deviation).
      In the bubble-free group, a significant decrease in left ventricular E/A ratio was the only significant change observed at post-dive assessment (−29%, P < 0.05; Fig. 3).

      Discussion

      The present study reports a significant increase of pulmonary arterial pressure in divers with ultrasonographic evidence of circulating gas bubbles after an uncomplicated recreational SCUBA dive. The increase in right ventricular afterload may, in turn, explain the increase in right ventricular internal dimensions, previously reported in divers with circulating bubbles, whose presence has been confirmed in the present study. A peculiarity of our study is the evaluation of a group of subjects of both sex and with a wide age range, being thus more representative of the real population of recreational SCUBA divers as compared to previous reports concerning young, male professional divers.
      • Dujic Z.
      • Obad A.
      • Palada I.
      • Valic Z.
      • Brubakk A.O.
      A single open sea air dive increases pulmonary artery pressure and reduces right ventricular function in professional divers.
      • Diesel D.A.
      • Ryles M.T.
      • Pilmanis A.A.
      • Balldin U.I.
      Non-invasive measurement of pulmonary artery pressure in humans with simulated altitude-induced venous gas emboli.
      The hypothesis of a cause and effect relationship between circulating bubbles and post-dive pulmonary arterial pressure increase would be strengthened by the demonstration of a significant correlation between bubble grade and pressure changes. The low number of subjects in each bubble-grade group prevented us to perform such an analysis; further studies, evaluating larger groups of divers, are therefore needed.
      Two possible mechanisms may be postulated to be at the basis of pulmonary arterial pressure increase in subjects with post-dive circulating bubbles. On one hand, a multiple microembolization might directly induce an increase of pulmonary vascular resistances.
      • Marabotti C.
      • Chiesa F.
      • Scalzini A.
      • Antonelli F.
      • Lari R.
      • Franchini C.
      • et al.
      Cardiac and humoral changes induced by recreational SCUBA diving.
      On the other hand, an indirect pressor effect, mediated by an endothelial damage induced by circulating bubbles, may be supposed. Experimental studies demonstrated that circulating gas bubbles might be responsible of endothelial layer injury by mechanical scraping, surfactant removal and platelet activation.
      • Utsonomiya T.
      • Krausz M.
      • Levine L.
      • Shepro D.
      • Hechtman H.B.
      Tromboxane mediation of cardiopulmonary effects of embolism.
      • Warren B.A.
      • Philp P.B.
      • Inwood M.J.
      The ultrastructural morphology of air embolism: platelet adhesion to the interface and endothelial damage.
      • Persson L.I.
      • Johansson B.B.
      • Hansson H.A.
      Ultrastructural studies on blood-brain barrier dysfunction and pathology after cerebral air embolism in the rat.
      Actually, the damaging potential of post-dive silent bubbles on pulmonary endothelium has previously been demonstrated in a study reporting, in divers with silent bubbles, a significant post-dive increase of plasma Angiotensin-Converting-Enzyme (ACE) activity.
      • Marabotti C.
      • Chiesa F.
      • Scalzini A.
      • Antonelli F.
      • Lari R.
      • Franchini C.
      • et al.
      Cardiac and humoral changes induced by recreational SCUBA diving.
      As a matter of fact, ACE is a glycoprotein highly concentrated in pulmonary endothelial cells that is usually considered a feasible marker of pulmonary endothelial damage,
      • Brizio-Molteni L.
      • Piano G.
      • Warpeha R.L.
      • Solliday N.H.
      • Molteni A.
      • Angelats J.
      • et al.
      Angiotensin-1-converting enzyme activity as index of pulmonary damage in thermal injury with or without smoke inhalation.
      associated to the development of pulmonary arterial hypertension in patients with connective tissue diseases.
      • Ozawa T.
      • Ninomiya Y.
      • Honma T.
      • Kikuchi M.
      • Sato T.
      • Nakano M.
      • et al.
      Increased serum angiotensin I-converting enzyme activity in patients with mixed connective tissue disease and pulmonary hypertension.
      Moreover, recent data indicate that post-decompression bubbles may interact with circulating microparticles and activate their pro-inflammatory potential, making them able to prime vascular injuries.
      • Thom S.R.
      • Yang M.
      • Bhopale V.M.
      • Huang S.
      • Milovanova T.N.
      Microparticles initiate decompression-induced neutrophil activation and subsequent vascular injuries.
      • Yang M.
      • Milovanova T.N.
      • Bogush M.
      • Uzun G.
      • Bhopale V.M.
      • Thom S.R.
      Microparticle enlargement and altered surface proteins after air decompression are associated with inflammatory vascular injuries.
      An increase of pulmonary arterial pressure due to the loss of endothelial control of vascular tone and to the vasoconstriction induced by platelet-derived vasoactive substances may thus be hypothesized.
      • Nossum V.
      • Hjelde A.
      • Brubakk A.O.
      Small amounts of venous gas embolism cause delayed impairment of endothelial function and increase polymorphonuclear neutrophil infiltration.
      • Vann R.D.
      • Butler F.K.
      • Mitchell S.J.
      • Moon R.E.
      Decompression illness.
      Since, in the present series, circulating bubbles were not present in a massive amount, an indirect vasoconstrictive effect seems to be more likely than the hypothesis of high-grade embolization of pulmonary arteriolar network. Nevertheless, as post-dive evaluation was performed after the peak of circulating bubbles detection (reported to be 30–40 min after surfacing),

      Marroni A, Cali Corleo R, Balestra C, Voellm E, Pieri M. Incidence of asymptomatic circulating venous gas emboli in unrestricted, uneventful recreational diving. DAN Europe’s Project SAFE DIVE first results. In: EUBS 2000 Proceedings. Diving and Hyperbaric Medicine, Proceedings of the XXVI Annual Scientific Meeting of the European Underwater and Baromedical Society. Cali Corleo R, editor. Malta 14–17 September, 2000. p. 9–15.

      the actual severity of the phenomenon may be underestimated and a direct pressor effect of multiple gas embolism cannot be excluded.
      Subjects with post-dive circulating bubbles resulted to have both mean age and pre-dive right ventricular dimension higher than subjects without bubbles. Owing to the relatively low number of subjects evaluated, this data may be the result of chance and may thus represent a limitation of the study. Nevertheless, from a different point of view, these same data may induce some stimulating speculations. It is a common observation, confirmed also by our data, that bubble prevalence and severity are not tightly related to immersion profile and that similar dives may induce a completely different bubble pattern in different subjects. From this observation, it may be hypothesized that some individual characters may predispose some subjects to the development of bubbles when exposed to a condition of inert gas supersaturation. According to decompression theories and to previous investigations, it may be speculated that age, sex, body fat and physical fitness may affect bubble formation and growth.
      • Carturan D.
      • Boussuges A.
      • Vanuxem P.
      • Bar-Hen A.
      • Burnet H.
      • Gardette B.
      Ascent rate, age, maximal oxygen uptake, adiposity, and circulating venous bubbles after diving.
      • Schellart N.A.
      • Vellinga T.P.
      • van Dijk F.J.
      • Sterk W.
      Doppler bubble grades after diving and relevance of body fat.
      In particular, a previous report, in which divers were divided in groups with different individual susceptibility to bubble formation, found that older divers were frequently observed to be “high-bubblers”.
      • Nishi R.Y.
      Doppler and ultrasonic bubble detection.
      Therefore, the trend to a higher age of subjects with post-dive silent bubbles may reflect the higher tendency to bubble formation of older subjects. Furthermore, on one hand Reeves et al.
      • Reeves J.T.
      • Linehan J.H.
      • Stenmark K.R.
      Distensibility of the normal human lung circulation during exercise.
      reported a reduced distensibility of the human lung circulation with aging, on the other hand a later systematic review
      • Kovacs G.
      • Berghold A.
      • Scheidl S.
      • Olschewski H.
      Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review.
      showed, in normal subjects, a significant direct relationship between age and pulmonary arterial pressure during effort (but not in basal conditions). Older subjects could therefore be exposed to an increased pulmonary arterial pressure both during diving (due to the increased pulmonary vascular reactivity to exercise) and after the dive (due to their higher bubble load). The significantly larger right ventricle observed at pre-dive assessment in subjects with subsequent development of post-dive bubbles might thus be a medium-term consequence of repeated pulmonary arterial pressure increases following the frequent recreational dives performed during summer by the divers studied in this report.
      The observation of a reduced post-dive left ventricular E/A ratio in both groups of divers suggests that this phenomenon is likely to be linked to diving itself rather than to the presence of circulating bubbles. From a pathophysiological point of view, such a change of diastolic filling pattern is consistent with a slower or delayed left ventricular relaxation
      • Oh J.K.
      • Hatle L.
      • Jamil Tajik A.
      • Little W.C.
      Diastolic heart failure can be diagnosed by comprehensive two-dimensional and Doppler echocardiography.
      and may be related to a change in heart rate or in left ventricular hemodynamic load. Actually, similar changes of diastolic filling pattern have been reported in case of increased afterload, reduced preload or increased heart rate.
      • Oh J.K.
      • Hatle L.
      • Jamil Tajik A.
      • Little W.C.
      Diastolic heart failure can be diagnosed by comprehensive two-dimensional and Doppler echocardiography.
      • Genovesi-Ebert A.
      • Marabotti C.
      • Palombo C.
      • Giaconi S.
      • Ghione S.
      Left ventricular filling: relationship with arterial blood pressure, left ventricular mass, age and body build.
      Since both systemic blood pressure and heart rate were not affected by diving, the observed change of left ventricular filling pattern may be ascribed to a post-dive preload reduction due to the well-known immersion natriuresis (whose effect on plasma volume has not fully compensated by ad libitum water drinking at the time of Doppler evaluation).
      In conclusion, the results of the present study confirm and extend previous reports indicating that post-dive circulating bubbles, although symptomless, have an easily detectable pathogenetic potential, being able of inducing unfavorable hemodynamic changes in the lesser circulation. The observation of a larger right ventricle at pre-dive evaluation in subjects developing post-dive bubbles could suggest possible medium-term consequences of habitual SCUBA diving, at least in older subjects. This hypothesis should be evaluated by further ad-hoc studies.

      Acknowledgments

      This paper is dedicated to the memory of Piergiorgio Data, whose involving enthusiasm and the strictness of his pioneering researches stimulated a number of disciples in pursuing his work on underwater physiology.

      Conflict of interest

      None declared.

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