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Risk of decompression sickness in the presence of circulating microbubbles

In this study, we examined the association between microbubbles formed in the circulation from a free gas phase and symptoms of altitude decompression sickness (DCS). In a subgroup of 59 males of mean (S.D) age 31.2 (5.8) years who developed microbubbles during exposure to 26.59 kPa (4.3 psi) under simulated extravehicular activities (EVA), symptoms of DCS occurred in 24 (41 percent) individuals. Spencer grade 1 microbubbles occurred in 4 (7 percent), grade 2 in 9 (15 percent), grade 3 in 15 (25 percent), and grade 4 in 31 (53 percent) of subjects. Survival analysis using Cox proportional hazards regression showed that individuals with less than grade 3 CMB showed 2.46 times (95 percent confidence interval = 1.26 to 5.34) higher risk of symptoms. This information is crucial for defining the risk of DCS for inflight Doppler monitoring under space EVA. Altitude decompression sickness (DCS) occurs when there is acute reduction in ambient pressure. The symptoms of DCS are due to the formation of a free gas phase (in the form of gas microbubbles) in tissues during decompression. Musculo-skeletal pain of bends is the commonest form of DCS in altitude exposures. In the space flight environment, there is a risk of DCS when astronauts decompress from the normobaric shuttle pressure into the hypobaric space suit pressure (currently about 29.65 kPa (4.3 psi) for extra-vehicular activities (EVA). This risk is counterbalanced by a judicious combination of prior denitrogenation and staged decompression. Studies of DCS are limited by the duration of the test at reduced pressure. Since only a proportion of subjects tested develop symptoms, the information on DCS is generally incomplete or 'censored'. Many studies employ Doppler ultrasound monitoring of the precordial area for detecting circulating microbubbles (CMB). Although the association between CMB and bends pain is not causal, CMB are frequently monitored during decompression. In this paper, we examine the association between CMB and symptoms of DCS under simulated EVA profiles.

Kumar, K. Vasantha↗

Time to detection of circulating microbubbles as a risk factor for symptoms of altitude decompression sickness

This study investigated the association between time at onset of circulating microbubbles (CMB) and symptoms of altitude decompression sickness (DCS), using Cox proportional hazard regression models. The study population consisted of 125 individuals who participated in direct ascent, simulated extravehicular activities profiles. Using individual CMB status as a time-dependent variable, we found that the hazard for symptoms increased significantly (at the end of 180 min at altitude) in the presence of CMB (Hazard Ratio = 29.59; 95 percent confidence interval (95 percent CI) = 7.66-114.27), compared to no CMB. Further examination was conducted on the subgroup of individuals who developed microbubbles during the test (n = 49), by using Cox regression. Individuals with late onset of CMB (greater than 60 min at altitude) showed a significantly reduced risk of symptoms (hazard ratio = 0.92; 95 percent CI = 0.89-0.95), compared to those with early onset (equal to or less than 60 min), while controlling for other risk factors. We conclude that time to detection of circulating microbubbles is an independent determinant of symptoms of DCS.

Kumar, K. V.↗

Aromatic proteinaceous surfactants stabilize long-lived gas microbubbles from natural sources

Three different types of protein-specific chemical tests were performed on long-lived gas microbubbles derived from aqueous solutions of agarose powder and from filtered aqueous extracts of Hawaiian forest soil. The separate protein-specific tests involved use of either 0.3% (w/v) ninhydrin, 100 microM methylene blue dye, or 0.7-1.0 M 2-hydroxy-5-nitrobenzyl bromide. The chemical test results obtained with each of the two natural substances, i.e., agarose powder and Hawaiian forest soil, were very similar and indicate that the biological surfactants which surround and stabilize long-lived gas microbubbles are proteinaceous compounds that contain, and whose surface activity depends upon, aromatic amino acid residues, particularly tryptophan.

Darrigo, J. S.↗

The effect of differences in time to detection of circulating microbubbles on the risk of decompression sickness

Circulating microbubbles (CMB) are frequently detected prior to the appearance of symptoms of Decompression Sickness (DCS). It is difficult to analyze the effect of CMB on symptoms due to differences in the time to detection of CMB. This paper uses survival analysis models to evaluate the risk of symptoms in the presence of CMB. Methods: Information on 81 exposures to an altitude of 6,400 m (6.5 psi) for a period of three hours, with simulated extravehicular activities, was examined. The presence or absence of CMB was included as a time dependent covariate of the Cox proportional hazards regression model. Using this technique, the subgroup of exposures with CMB was analyzed further. Mean (S.D.) time in minutes to onset of CMB and symptoms were 125 (63) and 165 (33) respectively, following the three hours exposure. The risk of symptoms (17/81) increased 14 times in the presence of CMB, after controlling for variations in time to detection of CMB. Further, the risk was lower when time to detection of CMB was greater than 60 minutes (risk ratio = 0.96; 95 percent confidence intervals = 0.94 - 0.99 0.99 P less than 0.01) compared to CMB before 60 minutes at altitude. Conclusions: Survival analysis showed that individual risk of DCS changes significantly due to variations in time to detection of CMB. This information is important in evaluating the risk of DCS in the presence of CMB.

Kumar, K. V.↗

Laboratory comparisons of acoustic and optical sensors for microbubble measurement

This paper presents the results of a recent comparison between three microbubble size spectrum measurement systems. These systems are the light-scattering bubble counter, the photographic bubble-imaging system, and the acoustic resonator array. Good agreement was formed among these three systems over the bubble size range appropriate for each system.

Su, Ming Yang↗

Patent Foramen Ovale: Association between the Degree of Shunt by Contrast Transesophageal Echocardiography and the Risk of Future Ischemic Neurologic Events

This study investigated whether there is an association between the degree of interatrial shunting across a patent foramen ovale, as determined by saline contrast transesophageal echocardiography, and the risk of subsequent systemic embolic events, including stroke. Thirty-four patients found to have patent foramen ovale during transesophageal echocardiography were divided into two groups on the basis of the maximum number of microbubbles in the left heart in any single frame after intravenous saline contrast injection: group 1 (n = 16) with a "large" degree of shunt (220 microbubbles) and group 2 (n = 18) with a "small" degree of shunt (23 but <20 microbubbles). Patients were followed up over a mean period of 21 months for subsequent systemic embolic events, including transient ischemic attack and stroke. Five (31%) of the patients with large shunts had subsequent ischemic neurologic events, whereas none of the patients with small shunts had embolic events (p= 0.03). These events occurred in spite of antiplatelet or anticoagulant therapy. We conclude that patients with a large degree of shunt across a patent foramen ovale, as determined by contrast transesophageal echocardiography, are at a significantly higher risk for subsequent adverse neurologic events compared with patients with a small degree of shunt.

Stone, David A.↗

Characteristics of Patent Foramen Ovale Associated with Cryptogenic Stroke: A Biplane Transesophageal Echocardiography Study

Patent foramen ovale is associated with ischemic stroke in patients without a clearly identifiable etiology for stroke (cryptogenic stroke). Paradoxical embolization is thought to be a potential mechanism. However, patent foramen ovale is also found in patients with known cause of stroke. Therefore, using contrast transesophageal echocardiography, we characterized the patent foramen ovale in cryptogenic stroke patients to assess morphological factors that may contribute to paradoxical embolization. Methods: Contrast transesophageal echocardiographic studies of 74 consecutive patients referred for ischemic stroke were reviewed. Twenty-three patients with patent foramen ovale were identified. These patients were classified as having strokes of determined origin or cryptogenic strokes according to criteria developed for the Stroke Data Bank of the National Institute of Neurological Disorders and Stroke. Separation of septum primum from secundum and the number of microbubbles appearing in left atrium were then quantitated. These parameters were compared between patients with cryptogenic stroke and those with known cause of stroke. Results: The patent foramen ovale dimension was significantly larger in patients with cryptogenic stroke compared with patients with an identifiable cause of stroke (2.1+/-1.7 mm versus 057+/-0.78 mm [mean+/-SD]; P<.01). The number of microbubbles was also greater in patients with cryptogenic stroke compared with patients with an identifiable cause of stroke (13.9+/-10.7 versus 1.62+/-0.8 [mean+/-SD]; P<.0005). Conclusions: Patients with cryptogenic stroke have larger patent foramen ovale with more extensive right-to-left inter-atrial shunting than patients with stroke of determined cause. Transesophageal echocardiographically identifiable characteristics of patent foramen ovale may be important in defining the clinical significance of individual patent foramina.

Homma, S.↗

Intravascular bubbles associated with intravenous injections and altitude

Ultrasonically detected microbubbles were more abundant in the pulmonary artery of dogs intravenously injected with 10 ml of saline than in the same noninjected control during 10,000 ft (3,048 m), 20,000 ft (6,096 m), and 40,000 ft (12,121 m) exposures. Continuous intravenous (i.v.) drip infusions also introduced many small bubbles. Since they may serve as 'nuclei' for visible intravascular bubble formation, are sometimes associated with decompression sickness, and are additionally considered undesirable, it would appear prudent to minimize i.v. injections immediately before flights. However, a 10-min delay before ascent wil reduce their number and a 60-min delay will insure their almost complete absence. Also, slow ascent, a 1-h denitrogenation time, or use of a degassed solution will help reduce their total number.

Cooke, J. P.↗

Metal shell technology

Metallic shells are fabricated for a size range from several millimeters down to less than 500 microns in diameter. The technology, developed at JPL, is based on the hollow-jet instability for the large-shell formation, and in addition, on the Bernoulli's force for the microbubble generation. Various materials were processed into hollow spheres, such as AL1100, tin, lead, and a metallic glass-forming alloy, AuPbSb. They exhibited a range of contrasting solidification behaviors and surface characteristics. Some of their potential applications will be explored in this paper.

Lee, M. C.↗

Exploring results of the possibility on detecting cosmic ray particles by acoustic way

It has been demonstrated experimentally and theoretically that high energy particles produce detectable sounds in water. However, no one has been able to detect an acoustic signal generated by a high energy cosmic ray particle in water. Results show that transient ultrasonic signals in a large lake or reservoir are fairly complex and that the transient signals under water may arise mainly from sound radiation from microbubbles. This field is not explored in detail. Perhaps, the sounds created by cosmic ray particles hide in these ultrasonic signals. In order to develop the technique of acoustic detection, it is most important to make a thorough investigation of these ultrasonic signals in water.

Jiang, Y.↗

Transpulmonary passage of venous air emboli

Twenty-seven paralyzed anesthetized dogs were embolized with venous air to determine the effectiveness of the pulmonary vasculature for bubble filtration or trapping. Air doses ranged from 0.05 to 0.40 ml/kg min in 0.05-ml increments with ultrasonic Doppler monitors placed over arterial vessels to detect any microbubbles that crossed the lungs. Pulmonary vascular filtration of the venous air infusions was complete for the lower air doses ranging from 0.05 to 0.30 ml/kg min. When the air doses were increased to 0.35 ml/kg min, the filtration threshold was exceeded with arterial spillover of bubbles occurring in 50 percent of the animals and reaching 71 percent for 0.40 ml/kg min. Significant elevations were observed in pulmonary arterial pressure and pulmonary vascular resistance. Systemic blood pressure and cardiac output decreased, whereas left ventricular end-diastolic pressure remained unchanged. The results indicate that the filtration of venous bubbles by the pulmonary vasculature was complete when the air infusion rates were kept below a threshold value of 0.30 ml/kg min.

Butler, B. D.↗

Advances in fluid dynamics

Various papers on advances in fluid dynamics are presented. Individual topics addressed include: nonunique solutions of the Euler equations; numerical solution of the biharmonic equation using a spectral multigrid method; finite-volume shape and placement for efficiency, accuracy, and physics; NND schemes and their application to numerical simulation of complex plume flow problems; symbolic analysis and computational algorithm construction; and velocity and mass flux distribution measurements of spherical glass beads in air flow in a 90-deg vertical-to-horizontal bend. Also discussed are: hyperbolic solution adaptive mesh generation; progress and future directions in CFD; numerical simulation of shock focusing; microbubble formation and splitting in a turbulent boundary layer for turbulence reduction; numerical study of spherical Taylor-Couette flow, trajectories of vortex lines beneath a free surface or above a plane; and a mathematical model for response of the coronary circulation to high sustained gravitational force fields.

Ballhaus, W. F., Jr.↗

Reducing Water/Hull Drag By Injecting Air Into Grooves

Proposed technique for reduction of friction drag on hydrodynamic body involves use of grooves and combinations of surfactants to control motion of layer on surface of such body. Surface contains many rows of side-by-side, evenly spaced, longitudinal grooves. Dimensions of grooves and sharpnesses of tips in specific case depends on conditions of flow about vessel. Requires much less air than does microbubble-injection method.

Reed, Jason C.↗

Analysis of the individual risk of altitude decompression sickness under repeated exposures

In a case-control study, researchers examined the risk of decompression sickness (DCS) in individual subjects with higher number of exposures. Of the 126 subjects, 42 showed one or more episodes of DCS. Examination of the exposure-DCS relationship by odds ratio showed a linear relationship. Stratification analysis showed that sex, tissue ratio, and the presence of Doppler microbubbles were cofounders of this risk. A higher number of exposures increased the risk of DCS in this analysis.

Kumar, K. Vasantha↗

Undercooling of acoustically levitated molten drops

It was observed that the acoustically levitated molten SCN (succinonitrile) drops can generally be undercooled to a degree where the impurities in the drop are responsible for the nucleation of the solid phase. However, it was also observed that ultrasound occasionally terminates undercooling of the levitated drops by initiating the nucleation of the solid at an undercooling level which is lower than that found for the nucleation catalyzed by the impurities in the drop. This premature nucleation can be explained by thermodynamic considerations which predict an increase in effective undercooling of the liquid upon the collapse of cavities. Pre-existing gas microbubbles which grow under the influence of ultrasound are suggested as the source of cavitation. The highly undercooled SCN drops can be utilized to measure the growth velocity of the solid in the deeply undercooled region including the hypercooled region.

Ohsaka, K.↗

The effect of exercise and rest duration on the generation of venous gas bubbles at altitude

BACKGROUND: Decompression, as occurs with aviators and astronauts undergoing high altitude operations or with deep-sea divers returning to surface, can cause gas bubbles to form within the organism. Pressure changes to evoke bubble formation in vivo during depressurization are several orders of magnitude less than those required for gas phase formation in vitro in quiescent liquids. Preformed micronuclei acting as "seeds" have been proposed, dating back to the 1940's. These tissue gas micronuclei have been attributed to a minute gas phase located in hydrophobic cavities, surfactant-stabilized microbubbles, or arising from musculoskeletal activity. The lifetimes of these micronuclei have been presumed to be from a few minutes to several weeks. HYPOTHESIS: The greatest incidence of venous gas emboli (VGE) will be detected by precordial Doppler ultrasound with depressurization immediately following lower extremity exercise, with progressively reduced levels of VGE observed as the interval from exercise to depressurization lengthens. METHODS: In a blinded cross-over design, 20 individuals (15 men, 5 women) at sea level exercised by performing knee-bend squats (150 knee flexes over 10 min, 235-kcal x h(-1)) either at the beginning, middle, or end of a 2-h chair-rest period without an oxygen prebreathe. Seated subjects were then depressurized to 6.2 psia (6,706 m or 22,000 ft altitude equivalent) for 120 min with no exercise performed at altitude. RESULTS: Of the 20 subjects with VGE in the pulmonary artery, 10 demonstrated a greater incidence of bubbles with exercise performed just prior to depressurization, compared with decreasing bubble grades and incidence as the interval of rest increased prior to depressurization. No decompression illness was reported. CONCLUSIONS: There is a significant increase in decompression-induced bubble formation at 6.2 psia when lower extremity exercise is performed just prior to depressurization as compared with longer rest intervals. Analysis indicated that micronuclei half-life is on the order of an hour under these hypobaric conditions.

Controlled Clinical Trial↗

Ventilation during simulated altitude, normobaric hypoxia and normoxic hypobaria

To investigate the possible effect of hypobaria on ventilation (VE) at high altitude, we exposed nine men to three conditions for 10 h in a chamber on separate occasions at least 1 week apart. These three conditions were: altitude (PB = 432, FIO2 = 0.207), normobaric hypoxia (PB = 614, FIO2 = 0.142) and normoxic hypobaria (PB = 434, FIO2 = 0.296). In addition, post-test measurements were made 2 h after returning to ambient conditions at normobaric normoxia (PB = 636, FIO2 = 0.204). In the first hour of exposure VE was increased similarly by altitude and normobaric hypoxia. The was 38% above post-test values and end-tidal CO2 (PET(CO2) was lower by 4 mmHg. After 3, 6 and 9 h, the average VE in normobaric hypoxia was 26% higher than at altitude (p < 0.01), resulting primarily from a decline in VE at altitude. The difference between altitude and normobaric hypoxia was greatest at 3 h (+ 39%). In spite of the higher VE during normobaric hypoxia, the PET(CO2) was higher than at altitude. Changes in VE and PET(CO2) in normoxic hypobaria were minimal relative to normobaric normoxia post-test measurements. One possible explanation for the lower VE at altitude is that CO2 elimination is relatively less at altitude because of a reduction in inspired gas density compared to normobaric hypoxia; this may reduce the work of breathing or alveolar deadspace. The greater VE during the first hour at altitude, relative to subsequent measurements, may be related to the appearance of microbubbles in the pulmonary circulation acting to transiently worsen matching. Results indicate that hypobaria per se effects ventilation under altitude conditions.

NASA Discipline Environmental Health↗

Method and apparatus for generating microshells of refractory materials

A system is described for forming accurately spherical and centered fluid-filled shells, especially of high melting temperature material. Material which is to form the shells is placed in a solid form in a container, and the material is rapidly heated to a molten temperature to avoid recrystallization and the possible generation of unwanted microbubbles in the melt. Immediately after the molten shells are formed, they drop through a drop tower whose upper end is heated along a distance of at least one foot to provide time for dissipation of surface waves on the shells while they cool to a highly viscous, or just above melting temperature so that the bubble within the shell will not rise and become off centered. The rest of the tower is cryogenically cooled to cool the shell to a solid state.

Lee, Mark C.↗