Exercise tolerance and pulmonary after deep saturation dives
gas exchange
EINAR THORSEN, JOHN HJELLE, KARE SEGADAL, AND AMUND GULSVIK Norwegian Underwater Technology Centre A/S, 5034 Ytre L&se&g; and Department of Thoracic Medicine, University of Bergen, 5021 Bergen, Norway THORSEN, EINAR, JOHN HJELLE, KARE SEGADAL, AND AMUND GULSVIK. Exercise tolerance and pulmonary gas ex-
changeafter deepsaturation dives.J. Appl. Physiol. 68(5): 18091814, 1990.-Pulmonary function and exercise tolerance were measuredbefore and after three saturation dives to a pressure of 3.7 MPa. The atmosphereswere heliox with partial pressures of oxygen of 40 kPa during the bottom phaseand 50 kPa during the compressionand decompressionphase.The bottom times were 3, 10, and 13 days. Decompressiontime was 13 days. Precordial Doppler monitoring was done daily during the decompression,and an estimate of the total bubble load on the pulmonary circulation was calculated as the accumulated sum of bubble scoresrecorded for each diver. Nine of the 18 divers had chest symptoms with retrosternal discomfort or nonproductive coughafter the dive. There were no changesin dynamic lung volumes.Transfer factor for carbon monoxide was significantly reduced from 12.3 * 1.2 to 10.9 * 1.3 mmol. kPa”e min-’ (P < O.Ol), and maximum oxygen uptake was reduced from 3.98 * 0.36 to 3.42 & 0.37 l/min STPD (P < 0.01) after the dives. Resting heart rate was increasedfrom 64 * 6 to 75 t 8 min’l (P < 0.01). The ventilatory requirements in relation to oxygen uptake and carbon dioxide elimination were significantly increased(P < 0.01) after the dives. The physiological deadspacefraction of tidal volume wassignificantly higher and showedan increasewith larger tidal volumes (P < 0.05). Anaerobic threshold estimated from gas exchangedata decreased from an oxygen uptake of 2.30 & 0.25 to 1.95k 0.28 l/min STPD (P < 0.05). There wasa significant correlation (Spearmanrank correlation) betweendecreasein maximum oxygen uptake and accumulatedbubble load on the pulmonary circulation (Rs = 0.60, P < 0.01). The results indicate a peripheral pulmonary lesionwith impaired gasexchange.
change abnormalities (13). Pathological conditions in the lungs induced by these processes can restrict inert gas elimination during decompression and may reduce the efficiency of the lung as a filter for venous gas microemboli, thereby increasing the risk of arterial embolization (4) In this study, pulmonary function and exercise tolerance were measured before and after three deep saturation dives to a depth equivalent to a pressure of 3.7 MPa (360 meters of sea water). The occurrence of venous gas microemboli during decompression was monitored by Doppler-ultrasound, and the effects of venous gas embolization on pulmonary function were analyzed. METHODS
The dives. Three dives to a depth equivalent to a pressure of 3.7 MPa were performed during 1986 in the Norwegian Underwater Technology Centre hyperbaric chamber complex. The compression time was 2 days and decompression time was 13 days. The bottom times were 3, 10, and 13 days. The atmosphere was heliox with a partial pressure of oxygen of 40 kPa during the bottom phase and 50 kPa during the compression and decompression phase. The decompression rate was 270 kPa/24 h with 6-h night stops from 3.7 to 0.24 MPa and a gradual decrease in the decompression rate from 0.24 MPa to the surface. During the dives both dry and wet tests of equipment and operational procedures were performed. In one of the dives, welding trials were performed as well. None of the divers was treated for decompression saturation diving; pulmonary function; exercise test; venous sickness and thereby received excessive oxygen exposure. microbubbles;Doppler monitoring In the dive that included welding trials, there was a possibility of inhalation of toxic and irritant gases. To avoid this, the divers breathed on masks with a separate THE EFFECTS on pulmonary function of a deep saturation gas supply all the time after welding was started. The dive are a result of the combined exposure to high amatmosphere was controlled for the presence of ozone, bient pressure with a phase of compression and de- nitrous oxides, and carbon monoxide before the divers compression and an artificial atmosphere where the par- were allowed to breathe freely in it again. The diving tial pressure of oxygen is usually elevated during de- procedures and the protocol for medical and physiological compression to facilitate inert gas elimination. The lungs monitoring of the divers were approved by the Regional are exposed to the high density of the breathing gas Ethical Review Committee. under pressure, thereby increasing the work of breathing, The divers. Eighteen experienced divers took part in and to concentrations of oxygen of 40-60 kPa, which the dives. Their mean age was 28 yr (range 23-34), mean may be toxic (12). During decompression, venous gas height 178 cm (range 170-193), and mean weight 77 kg microemboli may be generated that are subsequently (range 68-90). Five were smokers, 3 previous smokers, filtered in the pulmonary circulation where they can and 10 nonsmokers. Their final selection for the dives induce pulmonary inflammatory reactions and gas-ex- was based on a predive medical examination 4-6 wk 0161-7567/90 $1.50 Copyright 0 1990 the American Physiological Society
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PULMONARY
GAS
EXCHANGE
before the dives. They had all normal findings on clinical examination of heart and lungs, normal electrocardiogram (ECG), and a normal chest X-ray. Protocol. The divers base-line cardiopulmonary function was measured 4-6 wk before the dives (predive). At that time at least 4 wk had elapsed since their last saturation dive. They were reexamined l-3 days (postdive 1) and 4-6 wk (postdive 2) after the dive. After one of the dives, the postdive 2 examination was performed at another institute, and those results are not included in this paper. Lung function tests. Dynamic lung volumes were measured on a Gould 1000 IV Computerized Pulmonary Function Laboratory. The forced vital capacity (FVC), forced expired volume in 1 s (FE&) and mean forced expiratory flow between 25 and 75% of FVC (FEFZS-75) were taken as the best of at least three maneuvers not differing by more than 5% from the highest FVC (24). The transfer factor for carbon monoxide (Tlco) was measured by the single breath-holding technique (24). Effective alveolar volume (VA) was measured by the simultaneous helium dilution and transfer of carbon monoxide per unit lung volume calculated (Kco). Tlco was corrected to a hemoglobin concentration of 146 g/l. Exercise tests. Exercise testing was done on a Siemens Elema electrically braked bicycle with a 30-W increase in load every. 3rd min. Heart rate (HR), expired minute ventilation (VE), carbon dioxide and oxygen fractions of mixed expired gas, and end-tidal partial pressures of oxygen and carbon dioxide (PETE, and PET& were measured with a Beckmann MMC Horizon computerized pulmonary gas analyzer (16). Data were averaged over lmin intervals, and the results from the last minute at every work load were used for analysis. The derived parameters were oxygen consumption (7j02, l/min STPD), carbon dioxide elimination (VCO,, l/min STPD), respiratory exchange ratio (RER), breathing frequency (f), tidal volume (VT), and the .ventilatory equivalents for oxygen and carbon dioxide (VE/VO~ and VE/VCO~). The physiological dead space (VD/VT) was calculated from the Bohr equation with correction for valve dead space using PETIT* as an estimate of arterial partial pressure of carbon dioxide. Arterial blood gases were not measured. Anaerobic threshold (AT) was defined as the point where the vE/v02 curve began to rise while the vE/h02 curve remained constant (28). Another exercise protocol for measurement of maximum oxygen uptake (VOzmax) was used, and the test done on a treadmill the day after the bicycle exercise, using the same Beckmann MMC for measurement of gas exchange. The protocol began with a 6-min warm-up.period at 10 km/h with 0% inclination. If the subjects VO zrnax on the bicycle was 40-45 ml. min-’ kg-’ the first slope on the treadmill was set to 2%. If it was 45-50 ml. min-l kg-’ the slope was 4%, and if it was 50-55 ml. min-l kg” the slope was 6%. Thereafter the slope was increased by 2% every 3rd min. The total duration of the exercise test was then 9-12 min (3). The lung function and exercise tests for each examination were run by the same technicians and were always done during the morning at least 2 h after breakfast without tea or coffee. No smoking was allowed during
AFTER
SATURATION
DIVES
the last 2 h before the examination. Bubble detection. Detection of circulating venous microbubbles was as described in detail by Brubakk et al. (2) with the use of a multi frequency p ulsed Dopplerultrasound velocity meter (Alfred, Vingmed, Norway). High-pass filters, continuously adjustable from 200 to 600 Hz, were inserted to reduce noise. The transducers were placed inside the chamber and positioned by the divers themselves after a thorough predive training. Both the subject handling the probe inside the chamber and the operator outside the chamber could listen to the Doppler signal and communicate so that optimal positioning of the probe could be achieved. The signals were displayed as analog curves on an oscilloscope while being analyzed and recorded on magnetic tape. Recordings were made from several sites in a standardized sequence. Only recording from the precordial position is further described. This was done in the standing position. After the heart rate had stabilized to a resting rate, recording was made for 1 min. Thereafter, one deep knee bend was carried out and the signal recorded for 30 s. This maneuver was performed three times. The signals were interpreted by two investigators independently of each other. Bubble scores were classified according to the Kisman-Masurel code (18). When th .ere was disagreement between the investigators, the signals were reanalyzed from tape. The investigators were not blinded with respect to the subjects or to earlier scores. Bubbles were monitored during decompression twice daily in the first two dives and once daily in the third dive. Only the results from the afternoon recordings of the three dives were used for analysis. As a measure of the total bubble load on the pulmonary circulation for each subject, the accumulated bubble score was simply obtained by adding the scores day by day. A ranking of the divers could then be done (Fig. 1). Data processing and statistics. For comparison of data between the predive and the postdive examinations the paired Student’s t test was applied. Least squares linear correlation was used for comparison of continuous variables and the Spearman rank correlation (Rs )fordi screte variables (25). For comparison of exercise data, group W36 E 032 cn W -J28 E 224
l
l
l
S-4
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PULMONARY
intervals
for the independent
GAS
EXCHANGE
variables were defined: for
Vo2 and VCO~, increments of 0.5 l/min; for VE, increments of 20 l/min; for V.T, increments of 0.5 liters; and for 10% increments of Vo2 and VCO~ relative to their
maxima. The results are given as means t SD. Differences between examinations were calculated as difference from the mean. P < 0.05 was considered to be significant. RESULTS
Immediately after the dives the divers generally felt tired. Nine divers reported retrosternal discomfort and nonproductive cough provoked by deep inspiration or expiration. There were normal findings on clinical examination of heart and lungs and normal ECGs, apart from a sinus tachycardia. Resting heart rate was significantly increased from 64 t 6 to 75 t 8 min-’ (P c 0.01). Chest X-rays were normal for six divers after one of the dives but were not taken after the other dives. There was a slight decrease in hemoglobin concentration from 147 t 8 to 139 t 10 g/l (NS), and weight was also slightly reduced, from 77.2 t 5.3 to 75.7 t 6.1 kg (NS). Dynamic lung volumes were unchanged (Table l), but the Tlco was significantly reduced from a predive value of 12.3 t 1.2 to 10.9 t 1.3 mmolomin-’ kPa-’ at the postdiue 1 examination (P c 0.01). There were only small differences between the dives with a mean reduction in Tlco of 9.5, 11.1, and 13.6% (NS). Effective alveloar volume was unchanged, thereby giving a similar decrease in Kco of 10.5%. There were no significant differences between the predive and postdive 2 examination 4-6 wk after the dives. vo2 maxon treadmill exercise was reduced by 15.2% of the mean immediately after the dives, from 3.98 t 0.36 to 3.42 t 0.37 l/min (P < 0.01). Exercise was continued to the same maximum heart rate (191 t 8 vs. 189 t 11 min-l, NS) on each examination, and the RER exceeded 1.10 at the end of exercise for all subjects both predive and postdive. This was the case for both the treadmill and bicycle tests, with VO 2maxon the treadmill test being 11% higher and maximal heart rate being 4% higher on l
TABLE 1. Selected results from pulmonary function and exercise tests
Dynamic lung volumes FVC, liters FE&, liters FEFws, l/s Diffusion capacity -l. kpa-’ Tlcc, mmol .min . Kco, mmol mm -l. kpa-‘. 1-l VA, liters Bicycle exercise l
AFTER
SATURATION
DIVES
1811
the treadmill test compared with the bicycle test (Table 1). Maximal ventilation was lower immediately postdive (P < 0.02; Table l), and 14 of the 18 divers claimed that shortness of breath contributed to the discontinuation of the test, not general fatigue as was claimed on the predive and postdiue 2 examinations. Anaerobic threshold was also decreased from a i702 of 2.30 t 0.25 to 1.95 t 0.28 l/min (P < 0.05) but remained as the same fraction of vo 2max(65.3% vs. 68.9%). The bicycle test was designed to study details of parameters at different work loads in steady-state conditions. Resting heart rate was increased postdive. There was a linear relationship between heart rate and oxygen uptake, but the slope of the curve describing this relationship was increased postdive. The linear relationship between oxygen uptake and work load was likewise preserved and showed no difference. Ventilation was significantly increased in relation to oxygen uptake at all work loads, as well as in relation to carbon dioxide output (Fig. 2, A and B; P < 0.01). The increased ventilation was also reflected in a decreased PETco, and increased PETE, (Fig. 2, C and 0). There were no significant differences in the relationships between f and ventilation or between VT and ventilation (Fig. 2, E and F). However, the dead space fraction of VT was increased, the difference becoming significant (P c 0.05) and more pronounced as ventilation, and thereby VT, increased (Fig. 3). The measure of accumulated bubble score showed a wide interindividual variation (Fig. 1). The intraindividual variation in bubble score from day to day showed a small variation. There was also a wide interindividual variation in the time in decompression at which bubbles were first detected. The rank correlation showed significant correlation between accumulated bubble score and percent reduction in v02 max(Rs = 0.60, P C 0.01; Fig. 4). There was also a significant correlation between reduction in VO zrnax and the time in decompression at which bubbles were first detected (Rs = 0.46, P < 0.05). There was a significant correlation between decrease in v02 maxand decrease in Tlco (r = 0.46, P C 0.05) but not directly between bubble score and reduction in Tlco (Rs = 0.21). DISCUSSION
Postdive
Predive (18)
1 (18)
2 (12)
6.08kO.69 4.87t0.61 4.54t1.02
6.19rtO.50 4.892057 4.52t1.13
6.1OkO.50 4.7520.58 4.30t1.15
12.3t1.2 1.60t0.20 7.78t0.82
10.9+1.3t 1.44t0.18* 7.6120.65
11.5k1.3 1.51t0.21 7.62t0.70
3.52t0.41 2.83+0.57t 3.28kO.50 VO 2 max7 Vmin 135.2t19.0 119.5&19.6* 124.0t21.0 VE max9 bin 184k7 1811k6 186k7 HRmax, min-’ 2.3020.25 1.95-eO.28* 2.15kO.30 AT, I/min Values are means k SD for no. of subjects in parentheses. See text for definition of abbreviations. * Significantly different from predive W < 0.05). Significantlv different from nredive (P < 0.01).
Effects on pulmonary function reported after saturation dives in some cases have been an increase in the vital capacity (VC), attributed to a training effect of respiratory muscles by the increased work of breathing (7,27,29). More recently, Hyacinthe et al. (14) and Cotes et al. (7) have reported a reduction in pulmonary diffusion capacity after two dives to 3.1 MPa. The time for recovery of the diffusion capacity was shown to be at least 4 wk. Which part of the dive that is responsible for this effect is unknown, but it could be an expression of the oxygen toxicity effect. Fifty percent of the divers in this study had chest symptoms after surfacing, and all had objective findings of decreased pulmonary function and reduced exercise tolerance. There were no changes in dynamic lung volumes or effective VA. The reduction of Tloo must therefore be caused bv either impaired diffusion through the
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1812
PULMONARY
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GAS EXCHANGE
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2. A-R results from bicycle exercise test. Solid lines, predive; dotted lines, postdive 1. Mean for each group interval and its SD are shown. FIG.
alveolocapillary membrane or a reduced capillary blood volume available for diffusion. The pattern of changes in the ventilatory response to exercise challenge has many of the characteristics described in conditions with pulmonary arterial hypertension (11, 15, 20). The combination of sinus tachycardia, decreased Tloo, decreased Vo2 m8Xand AT, and increased ventilation with high VD/
VT has been described both in primary pulmonary hypertension and recurrent pulmonary thromboembolism. An increased alveoloarterial difference of partial pressure of oxygen should then be observed, but neither arterial blood gases nor oxygen saturation was measured during this study. During a dive several factors can impair the cardio-
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PULMONARY
‘f
w= . : : : : :
. : : : : :
.. .
-
GAS EXCHANGE
. . . : . : : : .
. ...-.**A.*= ::‘ :: : ,**: :: :: :.. .: : .:. .**
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FIG. 3. Physiological dead space (as percentage of tidal volume) as function of increasing tidal volume during exercise. Solid line, predive; dotted line, post&e 1. Mean for each group interval and its SD are shown.
OT 0
. S
v 10
. 1s
.
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FIG. 4. Relation between accumulated bubble score and reduction in maximal oxygen uptake.
pulmonary function. Physical activity is low during the long decompressions, and reductions of Qo~ max, and anaerobic threshold of this magnitude have been described as a detraining or bed rest effect (8). However, a reduction in Tlco and increased physiological dead space would not then be expected. A central limitation of oxygen supply to working muscles is possible, however, and may add to an effect of deconditioning of striated muscle. The effects of hyperoxia on the lung are several. The symptoms produced are those of a tracheobronchitis with retrosternal discomfort as the divers reported. The functional changes reported are reductions in VC and Tloo (5,23). After deep dives there is a tendency for increased VC, which is attributed to a training effect on respiratory muscles as seen after loaded breathing (19) and swimming training (6). This effect could then be opposed by an oxygen toxicity effect. On the other hand, there is no evidence of a significant reduction of VC in extended
AFTER
SATURATION
DIVES
1813
exposures to oxygen of concentrations below 50 kPa. In the study by Puy et al. (23), where a reduction in Tloo was demonstrated, Tlco was partitioned into its vascular and membrane components. The main reduction in Tlco was then attributed to the vascular component. Other studies also indicate that the capillary endothelial cell is the most vulnerable to hyperoxia with disruption of the endothelial lining and occlusion of capillary and small arteriolar lumina (17). Changes in Tloo may therefore be more sensitive than VC for detecting early effects of oxygen toxicity. Microvascular injury caused by oxygen could then explain the changes in pulmonary function after the dives. It was, however, not possible to quantitate this effect in this study as there were no significant differences in the reduction in Tlco between the three dives, and the range over which the divers oxygen exposure varied was very narrow. Venous gas microbubbles are a common occurrence in operational decompression procedures, both in diving and space activity (26). They have the potential for inducing inflammatory reactions in various tissues. The effects on pulmonary tissue of doses comparable to those encountered during operational decompressions are largely unknown, but it is known that massive air embolism induces pulmonary inflammation and edema (1, 22), and this is even used as an experimental model for adult respiratory distress syndrome. The indication of a correlation between accumulated bubble score and reduction in VO 2 max is suggestive of bubble effects on the lungs. Monitoring of bubbles for only short periods twice daily may not give a measure of actual bubble load; however, it provides an indication. Again, the capillary endothelial cell is the target cell for injury, and oxygen radicals are probably involved in the process of damage (9, 10). A raised partial pressure of oxygen might then potentiate this effect. The pattern of changes in the lung function parameters after the dives indicates a peripheral pulmonary lesion affecting gas exchange function. Conceivably, if significant pulmonary hypertension is associated with this lesion, passage of microemboli to the arterial circulation may be facilitated (13). This study demonstrates significant reduction in exercise tolerance and pulmonary function correlated with pulmonary microbubble load during the decompression. Oxygen toxicity and a detraining effect of the long decompression period could have contributed to this effect. We are grateful to the divers and the operational personnel from the Royal Navy, Norcem Comex, and the Norwegian Underwater Technology Centre. This work was supported by Norsk Hydro A/S, Statoil, and the Royal Norwegian Council for Scientific and Industrial Research. K. Segadal was supported by grants from the Norwegian Research Council for Science and the Humanities from 1986 to 1988, Hyperbaric Medical Research Programme, Grant 13.91.99-118. Address for reprint requests: E. Thorsen, Norwegian Underwater Technology Centre, Gravdalsveien B&5034 Ytre Laksevag, Norway. Received 9 January 1989; accepted in final form 2 January 1990. REFERENCES 1.
ALBERTINE, J. J., J. STAUB. Quantification
P. WIENER-KRONISH, K. KOIKE, AND N. C. of damage by air emboli to lung microvessels in anesthetized sheep. J. Appl. Physiol. 57: 1360-1368,19&L
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GAS EXCHANGE
R. PETERSON, A. GRIP, B. HOLAND, J. ONART. D. KUNKLE, AND S. TBNJUM. Gas bubbles in the circulation of divers after ascending excursions from 300 to 250 msw. J. Appl. Physiol. 60: 45-51, 1986. 3. BUCHFUHRER, M. J., J. E. HANSEN, T. E. ROBINSON, D. Y. SUE, K. WASSERMAN, AND B. J. WHIPP. Optimizing the exercise protocol for cardiopulmonary assessment. J. Appl. Physiol. 55: 1558-
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B. D., AND J. KATZ. Vascular pressures and passage of gas emboli through the pulmonary circulation. Undersea Biomed. Res. 15: 203-209,1988. 5. CALDWELL, P. R. B., W. L. LEE, JR., H. S. SCHILDKRAUT, AND E. R. ARCHIBALD. Changes in lung volume, diffusing capacity and blood gases in men breathing oxygen. J. Appl. Physiol. 21: l4771483,1966. 6. CLANTON,
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gas exchange
EINAR THORSEN, JOHN HJELLE, KARE SEGADAL, AND AMUND GULSVIK Norwegian Underwater Technology Centre A/S, 5034 Ytre L&se&g; and Department of Thoracic Medicine, University of Bergen, 5021 Bergen, Norway THORSEN, EINAR, JOHN HJELLE, KARE SEGADAL, AND AMUND GULSVIK. Exercise tolerance and pulmonary gas ex-
changeafter deepsaturation dives.J. Appl. Physiol. 68(5): 18091814, 1990.-Pulmonary function and exercise tolerance were measuredbefore and after three saturation dives to a pressure of 3.7 MPa. The atmosphereswere heliox with partial pressures of oxygen of 40 kPa during the bottom phaseand 50 kPa during the compressionand decompressionphase.The bottom times were 3, 10, and 13 days. Decompressiontime was 13 days. Precordial Doppler monitoring was done daily during the decompression,and an estimate of the total bubble load on the pulmonary circulation was calculated as the accumulated sum of bubble scoresrecorded for each diver. Nine of the 18 divers had chest symptoms with retrosternal discomfort or nonproductive coughafter the dive. There were no changesin dynamic lung volumes.Transfer factor for carbon monoxide was significantly reduced from 12.3 * 1.2 to 10.9 * 1.3 mmol. kPa”e min-’ (P < O.Ol), and maximum oxygen uptake was reduced from 3.98 * 0.36 to 3.42 & 0.37 l/min STPD (P < 0.01) after the dives. Resting heart rate was increasedfrom 64 * 6 to 75 t 8 min’l (P < 0.01). The ventilatory requirements in relation to oxygen uptake and carbon dioxide elimination were significantly increased(P < 0.01) after the dives. The physiological deadspacefraction of tidal volume wassignificantly higher and showedan increasewith larger tidal volumes (P < 0.05). Anaerobic threshold estimated from gas exchangedata decreased from an oxygen uptake of 2.30 & 0.25 to 1.95k 0.28 l/min STPD (P < 0.05). There wasa significant correlation (Spearmanrank correlation) betweendecreasein maximum oxygen uptake and accumulatedbubble load on the pulmonary circulation (Rs = 0.60, P < 0.01). The results indicate a peripheral pulmonary lesionwith impaired gasexchange.
change abnormalities (13). Pathological conditions in the lungs induced by these processes can restrict inert gas elimination during decompression and may reduce the efficiency of the lung as a filter for venous gas microemboli, thereby increasing the risk of arterial embolization (4) In this study, pulmonary function and exercise tolerance were measured before and after three deep saturation dives to a depth equivalent to a pressure of 3.7 MPa (360 meters of sea water). The occurrence of venous gas microemboli during decompression was monitored by Doppler-ultrasound, and the effects of venous gas embolization on pulmonary function were analyzed. METHODS
The dives. Three dives to a depth equivalent to a pressure of 3.7 MPa were performed during 1986 in the Norwegian Underwater Technology Centre hyperbaric chamber complex. The compression time was 2 days and decompression time was 13 days. The bottom times were 3, 10, and 13 days. The atmosphere was heliox with a partial pressure of oxygen of 40 kPa during the bottom phase and 50 kPa during the compression and decompression phase. The decompression rate was 270 kPa/24 h with 6-h night stops from 3.7 to 0.24 MPa and a gradual decrease in the decompression rate from 0.24 MPa to the surface. During the dives both dry and wet tests of equipment and operational procedures were performed. In one of the dives, welding trials were performed as well. None of the divers was treated for decompression saturation diving; pulmonary function; exercise test; venous sickness and thereby received excessive oxygen exposure. microbubbles;Doppler monitoring In the dive that included welding trials, there was a possibility of inhalation of toxic and irritant gases. To avoid this, the divers breathed on masks with a separate THE EFFECTS on pulmonary function of a deep saturation gas supply all the time after welding was started. The dive are a result of the combined exposure to high amatmosphere was controlled for the presence of ozone, bient pressure with a phase of compression and de- nitrous oxides, and carbon monoxide before the divers compression and an artificial atmosphere where the par- were allowed to breathe freely in it again. The diving tial pressure of oxygen is usually elevated during de- procedures and the protocol for medical and physiological compression to facilitate inert gas elimination. The lungs monitoring of the divers were approved by the Regional are exposed to the high density of the breathing gas Ethical Review Committee. under pressure, thereby increasing the work of breathing, The divers. Eighteen experienced divers took part in and to concentrations of oxygen of 40-60 kPa, which the dives. Their mean age was 28 yr (range 23-34), mean may be toxic (12). During decompression, venous gas height 178 cm (range 170-193), and mean weight 77 kg microemboli may be generated that are subsequently (range 68-90). Five were smokers, 3 previous smokers, filtered in the pulmonary circulation where they can and 10 nonsmokers. Their final selection for the dives induce pulmonary inflammatory reactions and gas-ex- was based on a predive medical examination 4-6 wk 0161-7567/90 $1.50 Copyright 0 1990 the American Physiological Society
1809
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1810
PULMONARY
GAS
EXCHANGE
before the dives. They had all normal findings on clinical examination of heart and lungs, normal electrocardiogram (ECG), and a normal chest X-ray. Protocol. The divers base-line cardiopulmonary function was measured 4-6 wk before the dives (predive). At that time at least 4 wk had elapsed since their last saturation dive. They were reexamined l-3 days (postdive 1) and 4-6 wk (postdive 2) after the dive. After one of the dives, the postdive 2 examination was performed at another institute, and those results are not included in this paper. Lung function tests. Dynamic lung volumes were measured on a Gould 1000 IV Computerized Pulmonary Function Laboratory. The forced vital capacity (FVC), forced expired volume in 1 s (FE&) and mean forced expiratory flow between 25 and 75% of FVC (FEFZS-75) were taken as the best of at least three maneuvers not differing by more than 5% from the highest FVC (24). The transfer factor for carbon monoxide (Tlco) was measured by the single breath-holding technique (24). Effective alveolar volume (VA) was measured by the simultaneous helium dilution and transfer of carbon monoxide per unit lung volume calculated (Kco). Tlco was corrected to a hemoglobin concentration of 146 g/l. Exercise tests. Exercise testing was done on a Siemens Elema electrically braked bicycle with a 30-W increase in load every. 3rd min. Heart rate (HR), expired minute ventilation (VE), carbon dioxide and oxygen fractions of mixed expired gas, and end-tidal partial pressures of oxygen and carbon dioxide (PETE, and PET& were measured with a Beckmann MMC Horizon computerized pulmonary gas analyzer (16). Data were averaged over lmin intervals, and the results from the last minute at every work load were used for analysis. The derived parameters were oxygen consumption (7j02, l/min STPD), carbon dioxide elimination (VCO,, l/min STPD), respiratory exchange ratio (RER), breathing frequency (f), tidal volume (VT), and the .ventilatory equivalents for oxygen and carbon dioxide (VE/VO~ and VE/VCO~). The physiological dead space (VD/VT) was calculated from the Bohr equation with correction for valve dead space using PETIT* as an estimate of arterial partial pressure of carbon dioxide. Arterial blood gases were not measured. Anaerobic threshold (AT) was defined as the point where the vE/v02 curve began to rise while the vE/h02 curve remained constant (28). Another exercise protocol for measurement of maximum oxygen uptake (VOzmax) was used, and the test done on a treadmill the day after the bicycle exercise, using the same Beckmann MMC for measurement of gas exchange. The protocol began with a 6-min warm-up.period at 10 km/h with 0% inclination. If the subjects VO zrnax on the bicycle was 40-45 ml. min-’ kg-’ the first slope on the treadmill was set to 2%. If it was 45-50 ml. min-l kg-’ the slope was 4%, and if it was 50-55 ml. min-l kg” the slope was 6%. Thereafter the slope was increased by 2% every 3rd min. The total duration of the exercise test was then 9-12 min (3). The lung function and exercise tests for each examination were run by the same technicians and were always done during the morning at least 2 h after breakfast without tea or coffee. No smoking was allowed during
AFTER
SATURATION
DIVES
the last 2 h before the examination. Bubble detection. Detection of circulating venous microbubbles was as described in detail by Brubakk et al. (2) with the use of a multi frequency p ulsed Dopplerultrasound velocity meter (Alfred, Vingmed, Norway). High-pass filters, continuously adjustable from 200 to 600 Hz, were inserted to reduce noise. The transducers were placed inside the chamber and positioned by the divers themselves after a thorough predive training. Both the subject handling the probe inside the chamber and the operator outside the chamber could listen to the Doppler signal and communicate so that optimal positioning of the probe could be achieved. The signals were displayed as analog curves on an oscilloscope while being analyzed and recorded on magnetic tape. Recordings were made from several sites in a standardized sequence. Only recording from the precordial position is further described. This was done in the standing position. After the heart rate had stabilized to a resting rate, recording was made for 1 min. Thereafter, one deep knee bend was carried out and the signal recorded for 30 s. This maneuver was performed three times. The signals were interpreted by two investigators independently of each other. Bubble scores were classified according to the Kisman-Masurel code (18). When th .ere was disagreement between the investigators, the signals were reanalyzed from tape. The investigators were not blinded with respect to the subjects or to earlier scores. Bubbles were monitored during decompression twice daily in the first two dives and once daily in the third dive. Only the results from the afternoon recordings of the three dives were used for analysis. As a measure of the total bubble load on the pulmonary circulation for each subject, the accumulated bubble score was simply obtained by adding the scores day by day. A ranking of the divers could then be done (Fig. 1). Data processing and statistics. For comparison of data between the predive and the postdive examinations the paired Student’s t test was applied. Least squares linear correlation was used for comparison of continuous variables and the Spearman rank correlation (Rs )fordi screte variables (25). For comparison of exercise data, group W36 E 032 cn W -J28 E 224
l
l
l
S-4
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PULMONARY
intervals
for the independent
GAS
EXCHANGE
variables were defined: for
Vo2 and VCO~, increments of 0.5 l/min; for VE, increments of 20 l/min; for V.T, increments of 0.5 liters; and for 10% increments of Vo2 and VCO~ relative to their
maxima. The results are given as means t SD. Differences between examinations were calculated as difference from the mean. P < 0.05 was considered to be significant. RESULTS
Immediately after the dives the divers generally felt tired. Nine divers reported retrosternal discomfort and nonproductive cough provoked by deep inspiration or expiration. There were normal findings on clinical examination of heart and lungs and normal ECGs, apart from a sinus tachycardia. Resting heart rate was significantly increased from 64 t 6 to 75 t 8 min-’ (P c 0.01). Chest X-rays were normal for six divers after one of the dives but were not taken after the other dives. There was a slight decrease in hemoglobin concentration from 147 t 8 to 139 t 10 g/l (NS), and weight was also slightly reduced, from 77.2 t 5.3 to 75.7 t 6.1 kg (NS). Dynamic lung volumes were unchanged (Table l), but the Tlco was significantly reduced from a predive value of 12.3 t 1.2 to 10.9 t 1.3 mmolomin-’ kPa-’ at the postdiue 1 examination (P c 0.01). There were only small differences between the dives with a mean reduction in Tlco of 9.5, 11.1, and 13.6% (NS). Effective alveloar volume was unchanged, thereby giving a similar decrease in Kco of 10.5%. There were no significant differences between the predive and postdive 2 examination 4-6 wk after the dives. vo2 maxon treadmill exercise was reduced by 15.2% of the mean immediately after the dives, from 3.98 t 0.36 to 3.42 t 0.37 l/min (P < 0.01). Exercise was continued to the same maximum heart rate (191 t 8 vs. 189 t 11 min-l, NS) on each examination, and the RER exceeded 1.10 at the end of exercise for all subjects both predive and postdive. This was the case for both the treadmill and bicycle tests, with VO 2maxon the treadmill test being 11% higher and maximal heart rate being 4% higher on l
TABLE 1. Selected results from pulmonary function and exercise tests
Dynamic lung volumes FVC, liters FE&, liters FEFws, l/s Diffusion capacity -l. kpa-’ Tlcc, mmol .min . Kco, mmol mm -l. kpa-‘. 1-l VA, liters Bicycle exercise l
AFTER
SATURATION
DIVES
1811
the treadmill test compared with the bicycle test (Table 1). Maximal ventilation was lower immediately postdive (P < 0.02; Table l), and 14 of the 18 divers claimed that shortness of breath contributed to the discontinuation of the test, not general fatigue as was claimed on the predive and postdiue 2 examinations. Anaerobic threshold was also decreased from a i702 of 2.30 t 0.25 to 1.95 t 0.28 l/min (P < 0.05) but remained as the same fraction of vo 2max(65.3% vs. 68.9%). The bicycle test was designed to study details of parameters at different work loads in steady-state conditions. Resting heart rate was increased postdive. There was a linear relationship between heart rate and oxygen uptake, but the slope of the curve describing this relationship was increased postdive. The linear relationship between oxygen uptake and work load was likewise preserved and showed no difference. Ventilation was significantly increased in relation to oxygen uptake at all work loads, as well as in relation to carbon dioxide output (Fig. 2, A and B; P < 0.01). The increased ventilation was also reflected in a decreased PETco, and increased PETE, (Fig. 2, C and 0). There were no significant differences in the relationships between f and ventilation or between VT and ventilation (Fig. 2, E and F). However, the dead space fraction of VT was increased, the difference becoming significant (P c 0.05) and more pronounced as ventilation, and thereby VT, increased (Fig. 3). The measure of accumulated bubble score showed a wide interindividual variation (Fig. 1). The intraindividual variation in bubble score from day to day showed a small variation. There was also a wide interindividual variation in the time in decompression at which bubbles were first detected. The rank correlation showed significant correlation between accumulated bubble score and percent reduction in v02 max(Rs = 0.60, P C 0.01; Fig. 4). There was also a significant correlation between reduction in VO zrnax and the time in decompression at which bubbles were first detected (Rs = 0.46, P < 0.05). There was a significant correlation between decrease in v02 maxand decrease in Tlco (r = 0.46, P C 0.05) but not directly between bubble score and reduction in Tlco (Rs = 0.21). DISCUSSION
Postdive
Predive (18)
1 (18)
2 (12)
6.08kO.69 4.87t0.61 4.54t1.02
6.19rtO.50 4.892057 4.52t1.13
6.1OkO.50 4.7520.58 4.30t1.15
12.3t1.2 1.60t0.20 7.78t0.82
10.9+1.3t 1.44t0.18* 7.6120.65
11.5k1.3 1.51t0.21 7.62t0.70
3.52t0.41 2.83+0.57t 3.28kO.50 VO 2 max7 Vmin 135.2t19.0 119.5&19.6* 124.0t21.0 VE max9 bin 184k7 1811k6 186k7 HRmax, min-’ 2.3020.25 1.95-eO.28* 2.15kO.30 AT, I/min Values are means k SD for no. of subjects in parentheses. See text for definition of abbreviations. * Significantly different from predive W < 0.05). Significantlv different from nredive (P < 0.01).
Effects on pulmonary function reported after saturation dives in some cases have been an increase in the vital capacity (VC), attributed to a training effect of respiratory muscles by the increased work of breathing (7,27,29). More recently, Hyacinthe et al. (14) and Cotes et al. (7) have reported a reduction in pulmonary diffusion capacity after two dives to 3.1 MPa. The time for recovery of the diffusion capacity was shown to be at least 4 wk. Which part of the dive that is responsible for this effect is unknown, but it could be an expression of the oxygen toxicity effect. Fifty percent of the divers in this study had chest symptoms after surfacing, and all had objective findings of decreased pulmonary function and reduced exercise tolerance. There were no changes in dynamic lung volumes or effective VA. The reduction of Tloo must therefore be caused bv either impaired diffusion through the
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1812
PULMONARY
A
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GAS EXCHANGE
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SATURATION
DIVES
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2. A-R results from bicycle exercise test. Solid lines, predive; dotted lines, postdive 1. Mean for each group interval and its SD are shown. FIG.
alveolocapillary membrane or a reduced capillary blood volume available for diffusion. The pattern of changes in the ventilatory response to exercise challenge has many of the characteristics described in conditions with pulmonary arterial hypertension (11, 15, 20). The combination of sinus tachycardia, decreased Tloo, decreased Vo2 m8Xand AT, and increased ventilation with high VD/
VT has been described both in primary pulmonary hypertension and recurrent pulmonary thromboembolism. An increased alveoloarterial difference of partial pressure of oxygen should then be observed, but neither arterial blood gases nor oxygen saturation was measured during this study. During a dive several factors can impair the cardio-
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PULMONARY
‘f
w= . : : : : :
. : : : : :
.. .
-
GAS EXCHANGE
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FIG. 3. Physiological dead space (as percentage of tidal volume) as function of increasing tidal volume during exercise. Solid line, predive; dotted line, post&e 1. Mean for each group interval and its SD are shown.
OT 0
. S
v 10
. 1s
.
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FIG. 4. Relation between accumulated bubble score and reduction in maximal oxygen uptake.
pulmonary function. Physical activity is low during the long decompressions, and reductions of Qo~ max, and anaerobic threshold of this magnitude have been described as a detraining or bed rest effect (8). However, a reduction in Tlco and increased physiological dead space would not then be expected. A central limitation of oxygen supply to working muscles is possible, however, and may add to an effect of deconditioning of striated muscle. The effects of hyperoxia on the lung are several. The symptoms produced are those of a tracheobronchitis with retrosternal discomfort as the divers reported. The functional changes reported are reductions in VC and Tloo (5,23). After deep dives there is a tendency for increased VC, which is attributed to a training effect on respiratory muscles as seen after loaded breathing (19) and swimming training (6). This effect could then be opposed by an oxygen toxicity effect. On the other hand, there is no evidence of a significant reduction of VC in extended
AFTER
SATURATION
DIVES
1813
exposures to oxygen of concentrations below 50 kPa. In the study by Puy et al. (23), where a reduction in Tloo was demonstrated, Tlco was partitioned into its vascular and membrane components. The main reduction in Tlco was then attributed to the vascular component. Other studies also indicate that the capillary endothelial cell is the most vulnerable to hyperoxia with disruption of the endothelial lining and occlusion of capillary and small arteriolar lumina (17). Changes in Tloo may therefore be more sensitive than VC for detecting early effects of oxygen toxicity. Microvascular injury caused by oxygen could then explain the changes in pulmonary function after the dives. It was, however, not possible to quantitate this effect in this study as there were no significant differences in the reduction in Tlco between the three dives, and the range over which the divers oxygen exposure varied was very narrow. Venous gas microbubbles are a common occurrence in operational decompression procedures, both in diving and space activity (26). They have the potential for inducing inflammatory reactions in various tissues. The effects on pulmonary tissue of doses comparable to those encountered during operational decompressions are largely unknown, but it is known that massive air embolism induces pulmonary inflammation and edema (1, 22), and this is even used as an experimental model for adult respiratory distress syndrome. The indication of a correlation between accumulated bubble score and reduction in VO 2 max is suggestive of bubble effects on the lungs. Monitoring of bubbles for only short periods twice daily may not give a measure of actual bubble load; however, it provides an indication. Again, the capillary endothelial cell is the target cell for injury, and oxygen radicals are probably involved in the process of damage (9, 10). A raised partial pressure of oxygen might then potentiate this effect. The pattern of changes in the lung function parameters after the dives indicates a peripheral pulmonary lesion affecting gas exchange function. Conceivably, if significant pulmonary hypertension is associated with this lesion, passage of microemboli to the arterial circulation may be facilitated (13). This study demonstrates significant reduction in exercise tolerance and pulmonary function correlated with pulmonary microbubble load during the decompression. Oxygen toxicity and a detraining effect of the long decompression period could have contributed to this effect. We are grateful to the divers and the operational personnel from the Royal Navy, Norcem Comex, and the Norwegian Underwater Technology Centre. This work was supported by Norsk Hydro A/S, Statoil, and the Royal Norwegian Council for Scientific and Industrial Research. K. Segadal was supported by grants from the Norwegian Research Council for Science and the Humanities from 1986 to 1988, Hyperbaric Medical Research Programme, Grant 13.91.99-118. Address for reprint requests: E. Thorsen, Norwegian Underwater Technology Centre, Gravdalsveien B&5034 Ytre Laksevag, Norway. Received 9 January 1989; accepted in final form 2 January 1990. REFERENCES 1.
ALBERTINE, J. J., J. STAUB. Quantification
P. WIENER-KRONISH, K. KOIKE, AND N. C. of damage by air emboli to lung microvessels in anesthetized sheep. J. Appl. Physiol. 57: 1360-1368,19&L
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1814
PULMONARY
GAS EXCHANGE
R. PETERSON, A. GRIP, B. HOLAND, J. ONART. D. KUNKLE, AND S. TBNJUM. Gas bubbles in the circulation of divers after ascending excursions from 300 to 250 msw. J. Appl. Physiol. 60: 45-51, 1986. 3. BUCHFUHRER, M. J., J. E. HANSEN, T. E. ROBINSON, D. Y. SUE, K. WASSERMAN, AND B. J. WHIPP. Optimizing the exercise protocol for cardiopulmonary assessment. J. Appl. Physiol. 55: 1558-
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T. L., G. F. DIXON, J. DRAKE, AND J. E. GADEK. Effects of swim training on lung volumes and inspiratory muscle conditioning. J. Appl. Physiol. 62: 39-46, 1987. 7. COTES, J. E., I. S. DAVEY, J. W. REED, AND M. ROOKS. Respiratory effects of a single saturation dive to 300 m. Br. J. Ind. Med. 44: 76-82,1987. 8. COYLE, E. F., W. H. MARTIN, AND J. 0. HOLLOSZY. Effects
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