An explicitly multi-component arterial gas embolus dissolves much more slowly than its one-component approximation.

We worked out the growth and dissolution rates of an arterial gas embolism (AGE), to illustrate the evolution over time of its size and composition, and the time required for its total dissolution. We did this for a variety of breathing gases including air, pure oxygen, Nitrox and Heliox (each over a range of oxygen mole fractions), in order to assess how the breathing gas influenced the evolution of the AGE. The calculations were done by numerically integrating the underlying rate equations for explicitly multi-component AGEs, that contained a minimum of three (water, carbon dioxide and oxygen) and a maximum of five components (water, carbon dioxide, oxygen, nitrogen and helium). The rate equations were straight-forward extensions of those for a one-component gas bubble. They were derived by using the Young-Laplace equation and Dalton's law for the pressure in the AGE, the Laplace equation for the dissolved solute concentration gradients in solution, Henry's law for gas solubilities, and Fick's law for diffusion rates across the AGE/arterial blood interface. We found that the 1-component approximation, under which the contents of the AGE are approximated by its dominant component, greatly overestimates the dissolution rate and underestimates the total dissolution time of an AGE. This is because the 1-component approximation manifestly precludes equilibration between the AGE and arterial blood of the inspired volatile solutes (O2, N2, He) in arterial blood. Our calculations uncovered an important practical result, namely that the administration of Heliox, as an adjunct to recompression therapy for treating a suspected N2-rich AGE must be done with care. While Helium is useful for preventing nitrogen narcosis which can arise in aggressive recompression therapy wherein the N2 partial pressure can be quite high (e.g.∼5 atm), it also temporarily expands the AGE, beyond the expansion arising from the use of Oxygen-rich Nitrox. For less aggressive recompression therapy wherein nitrogen narcosis is not a significant concern, Oxygen-rich Nitrox is to be preferred, both because it does not temporarily expand the AGE as much as Heliox, and because it is much cheaper and more conservation-minded.

Hypoxic storage of erythrocytes slows down storage lesions and prolongs shelf-life.

Conventional storage conditions of erythrocytes cause storage lesions. We propose that hypoxic storage conditions, involving removal of oxygen and replacement with helium, the changes in stored erythrocytes under hypoxic condition were observed and assessed. Erythrocytes were divided into two equal parts, then stored in conventional and hypoxic conditions, separately. Blood gas analysis, hemorheology, and hemolysis were performed once a week. Energy metabolism and membrane damage were monitored by enzyme-linked immunosorbent assay. Phosphatidylserine exposure was measured by flow cytometry. P50 was measured and the oxygen dissociation curve (ODC) plotted accordingly. Erythrocyte morphology was observed microscopically. In the 9th week of storage, the hemolysis of the hypoxia group was 0.7%; lower (p < .05) than that of the control group and still below the threshold of quality requirements. The dissolved oxygen and pO2 were only 1/4 of that in the control group (p < .01); the adenosine triphosphate, glucose, and lactic acid levels were decreased (p < .05), while the 2,3-diphosphoglycerate levels were increased relative to that in the control group (p < .01). There were no statistically significant differences in membrane damage, deformability, and aggregation between the two groups. In addition, the ODC of the two groups was shifted to the left but this difference was not statistically different. Basically similar to the effect of completely anaerobic conditions. Erythrocytes stored under hypoxic conditions could maintain a relatively stable state with a significant decrease in hemolysis, reduction of storage lesions, and an increase in shelf-life.

Helium induces preconditioning in human endothelium in vivo.

AIMS: Helium protects myocardium by inducing preconditioning in animals. We investigated whether human endothelium is preconditioned by helium inhalation in vivo. METHODS AND RESULTS: Forearm ischemia-reperfusion (I/R) in healthy volunteers (each group n = 10) was performed by inflating a blood pressure cuff for 20 min. Endothelium-dependent and endothelium-independent responses were measured after cumulative dose-response infusion of acetylcholine and sodium nitroprusside, respectively, at baseline and after 15 min of reperfusion using strain-gauge, venous occlusion plethysmography. Helium preconditioning was applied by inhalation of helium (79% helium, 21% oxygen) either 15 min (helium early preconditioning [He-EPC]) or 24 h before I/R (helium late preconditioning). Additional measurements of He-EPC were done after blockade of endothelial nitric oxide synthase. Plasma levels of cytokines, adhesion molecules, and cell-derived microparticles were determined. Forearm I/R attenuated endothelium-dependent vasodilation (acetylcholine) with unaltered endothelium-independent response (sodium nitroprusside). Both He-EPC and helium late preconditioning attenuated I/R-induced endothelial dysfunction (max increase in forearm blood flow in response to acetylcholine after I/R was 180 ± 24% [mean ± SEM] without preconditioning, 573 ± 140% after He-EPC, and 290 ± 32% after helium late preconditioning). Protection of helium was comparable to ischemic preconditioning (max forearm blood flow 436 ± 38%) and was not abolished after endothelial nitric oxide synthase blockade. He-EPC did not affect plasma levels of cytokines, adhesion molecules, or microparticles. CONCLUSION: Helium is a nonanesthetic, nontoxic gas without hemodynamic side effects, which induces early and late preconditioning of human endothelium in vivo. Further studies have to investigate whether helium may be an instrument to induce endothelial preconditioning in patients with cardiovascular risk factors.

A gas chromatography-thermal conductivity detection method for helium detection in postmortem blood and tissue specimens.

In cases of death by inert gas asphyxiation, it can be difficult to obtain toxicological evidence supporting assignment of a cause of death. Because of its low mass and high diffusivity, and its common use as a carrier gas, helium presents a particular challenge in this respect. We describe a rapid and simple gas chromatography-thermal conductivity detection method to qualitatively screen a variety of postmortem biological specimens for the presence of helium. Application of this method is demonstrated with three case examples, encompassing an array of different biological matrices.

Development of hyperpolarized noble gas MRI.

Magnetic resonance imaging using the MR signal from hyperpolarized noble gases 129Xe and 3He may become an important new diagnostic technique. Alex Pines (adapting the hyperpolarization technique pioneered by William Happer) presented MR spectroscopy studies using hyperpolarized 129Xe. The current authors recognized that the enormous enhancement in the delectability of 129Xe, promised by hyperpolarization, would solve the daunting SNR problems impeding their attempts to use 129Xe as an in vivo MR probe, especially in order to study the action of general anesthetics. It was hoped that hyperpolarized 129Xe MRI would yield resolutions equivalent to that achievable with conventional 1H2O MRI, and that xenon's solubility in lipids would facilitate investigations of lipid-rich tissues that had as yet been hard to image. The publication of hyperpolarized 129Xe images of excised mouse lungs heralded the emergence of hyperpolarized noble-gas MRI. Using hyperpolarized 3He, researchers have obtained images of the lung gas space of guinea pigs and of humans. Lung gas images from patients with pulmonary disease have recently been reported. 3He is easier to hyperpolarize than 129Xe, and it yields a stronger MR signal, but its extremely low solubility in blood precludes its use for the imaging of tissue. Xenon, however, readily dissolves in blood, and the T1, of dissolved 129Xe is long enough for sufficient polarization to be carried by the circulation to distal tissues. Hyperpolarized 129Xe dissolved-phase tissue spectra from the thorax and head of rodents and humans have been obtained, as have chemical shift 129 Xe images from the head of rats. Lung gas 129Xe images of rodents, and more recently of humans, have been reported. Hyperpolarized 129Xe MRI (HypX-MRI) may elucidate the link between the structure of the lung and its function. The technique may also be useful in identifying ventilation-perfusion mismatch in patients with pulmonary embolism, in staging and tracking the success of therapeutic approaches in patients with chronic obstructive airway diseases, and in identifying candidates for lung transplantation or reduction surgery. The high lipophilicity of xenon may allow MR investigations of the integrity and function of excitable lipid membranes. Eventually, HypX-MRI may permit better imaging of the lipid-rich structures of the brain. Cortical brain function is one perfusion-dependent phenomena that may be explored with hyperpolarized 129Xe MR. This leads to the exciting possibility of conducting hyperpolarized 129Xe functional MRI (HypX-fMRI) studies.

Biomedical imaging using hyperpolarized noble gas MRI: pulse sequence considerations.

Hyperpolarized noble gas MRI is a new technique for imaging of gas spaces and tissues that have been hitherto difficult to image, making it a promising diagnostic tool. The unique properties of hyperpolarized species, particularly the non-renewability of the large non-equilibrium spin polarization, raises questions about the feasibility of hyperpolarized noble gas MRI methods. In this paper, the critical issue of T1 relaxation is discussed and it is shown that a substantial amount of polarization should reach the targets of interest for imaging. We analyse various pulse sequence designs, and point out that total scan times can be decreased so that they are comparable or shorter than tissue T1 values. Pulse sequences can be optimized to effectively utilize the non-renewable hyperpolarization, to enhance the SNR, and to eliminate image artifacts. Hyperpolarized noble gas MRI is concluded to be quite feasible.

Breathing a mixture of inert gases: disproportionate diffusion into decompression bubbles.

To study the consequences of diving with gas mixtures, we simulated growth of decompression bubbles using an equation system that accounts for major determinants of bubble behavior. When breathing a mixture, bubbles are smaller than expected from linear interpolation between bubbles with either of the unmixed component gases because of disproportionate diffusion effects: a) When few bubbles form, the inert gas that permeates fastest becomes over-represented, relative to the breathing gas, inside bubbles during growth; this slows further entrance of the fast gas and enhances entrance of the slower gas. b) With N2-He mixtures and few bubbles, the over-represented gas is He in aqueous tissue, but is N2 in lipid tissue. c) When many bubbles form, the over-represented gas is the one with higher tissue solubility. Our simulations indicate that the smallest bubbles always occur with breathing of one of the component gases, but which gas that is depends on whether the tissue is lipid or aqueous and whether few or many bubbles form.

A comparison of the hemodynamic and ventilatory effects of abdominal insufflation with helium and carbon dioxide in young swine.

Abdominal CO2 insufflation has been shown to cause hypercarbia, acidemia, and decreased oxygenation in a pediatric animal model. Such metabolic derangements have prompted a search for alternative insufflation gases. This study compares the hemodynamic and ventilatory changes that occur during pneumoperitoneum with CO2 and helium. Four juvenile swine were intubated and given general anesthesia. Minute ventilation was adjusted to obtain a baseline Pco2 of between 32 and 36 mm Hg, and was kept constant for the duration of the experiment. The subjects initially were insufflated with CO2 or helium at a pressure of 10 mm Hg. Peak ventilatory pressure, end-tidal CO2 (ETCO2) arterial pH, Pco2, Po2, and right atrial and inferior vena caval pressures were measured before and during a 1-hour insufflation period. After desufflation, Pco2 and pH were restabilized. The same parameters were then measured during reinsufflation with the alternate gas. CO2 insufflation caused significant decreases in pH, from 7.51 +/- 0.03 to 7.32 +/- 0.06, and Po2 increased from 261 +/- 49 to 189 +/- 33 mm Hg. Pco2 increased from 35.0 +/- 1.4 to 57.9 +/- 6.3 mm Hg. ETCO2 also increased, from 29.0 +/- 2.2 to 47.2 +/- 5.0 mm Hg. Helium insufflation caused pH to decrease from 7.51 +/- 0.01 to 7.42 +/- 0.04. Pco2 increased from 32.8 +/- 0.8 to 43.5 +/- 3.9 mm Hg, and ETCO2 increased from 27.8 +/- 0.5 to 36.8 +/- 3.1 mm Hg. These alterations were significantly less than those with CO2 pneumoperitoneum. Po2 decreased as well-from 266 +/- 30 to 212 +/- 21 mm Hg. During insufflation with both gases, peak ventilatory pressure and right atrial pressure increased significantly. Abdominal insufflation with CO2 or helium causes hypercarbia, acidemia, and increased ETCO2 in this juvenile animal model. These derangements are significantly less with helium. This gas may prove to be the more suitable insufflation agent for pediatric patients.

Prospective comparison of helium versus carbon dioxide pneumoperitoneum.

BACKGROUND: During prolonged laparoscopic operations with carbon dioxide (CO2) pneumoperitoneum (PP), hypercapnia with significant acidosis has been reported to occur in some patients with pulmonary dysfunction. An alternate inert insufflation gas like helium (He) could avoid this problem. METHODS: This prospective, IRB-approved study compared the cardiopulmonary response in 20 patients with both CO2 and He PP. With the minute ventilation held constant, baseline arterial blood gases and ventilatory and cardiac parameters were obtained after anesthetic induction but prior to CO2 PP. All values were repeated at 20 to 30 and 40 to 60-minute intervals after the insufflation of CO2 PP, then again during He PP. Values were compared by a paired t test analysis. RESULTS: Patients experienced significant hypercapnia during CO2 PP when compared with baseline arterial blood gases, but all values returned to baseline levels during He PP. CONCLUSIONS: He PP is an effective alternative to CO2 PP for a laparoscopic cholecystectomy avoiding CO2 retention and subsequent acidosis. Carbon dioxide retention may be dangerous in patients with pulmonary dysfunction who undergo laparoscopy.

Role of molecular diffusion in conventional and high frequency ventilation.

The influence of molecular diffusion on gas-mixing during conventional mechanical ventilation (CMV) and high frequency ventilation (HFV) was studied by observing the wash-in of six poorly soluble, inert gases in arterial blood. Anesthetized dogs were ventilated either with CMV or HFV. Following a step change in inspired gas composition, the increase in arterial concentrations of hydrogen, helium, methane, ethane, isobutane, and sulfur hexafluoride was determined by gas chromatography. The relative gas diffusivities encompassed a range of almost one order of magnitude. Propane, present in inspired gas during both the control and wash-in phases, served as an internal reference for calculation of blood tracer concentrations. The wash-in of all six inert gases followed a single exponential time course during both CMV and HFV. The rate of wash-in of each gas decreased with increasing molecular weight (MW). The relationship of rate constants to a measure of relative diffusivity (MW-0.5) was significantly different than zero for both types of ventilation. The slope of this relationship was three times larger for CMV than HFV, indicating that molecular diffusion has a greater role in gas mixing during ventilation with large tidal volumes. Diffusion has a minor role in gas mixing during high frequency ventilation with small tidal volumes. Demonstration of the presence of gas separation secondary to molecular diffusion during HFV is enhanced by measuring wash-in, rather than wash-out, of inert gases because gas separation is likely to be obscured as exhaled gases pass through the well-mixed central airways during gas wash-out.

The sloping alveolar plateau of tracer gases washed out from mixed venous blood in man.

We have investigated the slope of the alveolar plateau for inert tracer gases that were washed out from mixed venous blood. Two pairs of tracer gases were used (He, SF6) and (C2H2, Freon 22). The gases of each pair share almost the same blood-gas partition coefficient but they have different diffusive properties in the gas phase. The experiments were performed in healthy subjects at rest and at three levels of exercise (75, 150, 225 W). Each experiment started with the alveolar washin of the tracer gases by adding these gases to inspired air. This washin was continued for several minutes in order to dissolve sufficient amounts of the tracer gases in the body tissues. Subsequently, the tracer gases were washed out. In this paper, the slopes of the alveolar plateaus are defined as the relative increase of the concentration per second. Steeper slopes were found for the heavier gases (SF6 and Freon 22) in comparison with those for the lighter gases of the two pairs (He and C2H2). This finding may be ascribed to the contribution of diffusion-limited gas mixing in the lung to the slope of the alveolar plateau. For each gas, the slope for the first expiration during washout (alveolar washout) was considerably smaller than that for the later part of washout (mixed venous washout), and the difference amounts to about 56% and 76% of the slope during mixed venous washout at rest and at the highest level of exercise, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of blood flow on cutaneous permeability to inert gas.

A thermally regulated Plexiglas chamber was designed for investigation of transcutaneous diffusion of N2 and helium (He) in the human hand. Influence of cutaneous blood flow in this process was studied simultaneously with gas diffusion measurements. Changes in cutaneous blood flow (Q, in ml X min-1 X 100 ml tissue-1) were effected by altering ambient temperature (T) from 20 to 40 degrees C (Q = 0.08 X 100.07T). We found that the rate of inert gas diffusion through human skin, expressed as conductance (G, in ml STPD X h-1 X m-2 X atm-1), increases exponentially as a function of blood flow, and was indistinguishable between He and N2 (G = 21.19 X 100.0124Q). The permeability, diffusion coefficient per unit diffusion distance (D/h, in cm/h), also rose exponentially as a function of blood flow. But permeability for He (D/h = 0.1748 X 100.0203Q) was greater than that for N2 (D/h = 0.1678 X 100.0114Q). As cutaneous blood flow rises, because of increased temperature, the apparent diffusion distance falls linearly for both N2 and He. The change is more prominent for He than for N2 diffusion. Estimated replacement time for the body stores of N2 by transcutaneous diffusion alone was shortened from 26.8 h at 31 degrees C to 15.1 h at 37 degrees C. It is suggested from this study that beneficial results may be derived during decompression procedure 1) by maintaining an appropriate transcutaneous pressure gradient of inert gases, and 2) by elevating ambient temperature.

Solubility of helium, argon, and sulfur hexafluoride in human blood measured by mass spectrometry.

A method has been developed to measure the solubility coefficients of gases in liquids by respiratory mass spectrometry. A sample (2.5 ml) pf the test liquid, equilibrated with a test gas mixture, is injected into a sealed flask (approximately 140 ml) for extraction by equilibration. The reequilibrated gas phase in the flask is analyzed by a mass spectrometer. Separately, an equal volume (2.5 ml) of the equilibrating test gas mixture is injected into a larger sealed flask (approximately ll liter) where it is mixed and then analyzed by the mass spectrometer. Solubility in the liquid is calculated from the ratio of mass spectrometer readings in both flasks and the ratio of flask volumes. The ratio of volumes of the small and the large flasks is made similar to the gas/liquid partition coefficient whereby the mass spectrometer readings in both become similar. With this approach, errors due to amplifier and mass spectrometer nonlinearity are greatly attenuated. The method was used to measure the solubility of helium, argon, and sulfur hexafluoride in distilled water, human plasma, and human blood.

Prlonged bubble production by transient isobaric counter-equilibration of helium against nitrogen.

The production of systemic gas bubbles by isobaric counter-equilibration of helium against 5 atmospheres saturated nitrox (0.3 ATA O2 in both mixes) in awake goats was demonstrated. Sixteen animal exposures (8 dives, 2 animals per dive) to a sudden isobaric gas switch from saturation on N2 to He were conducted; 8 saturations occurred at 132 fsw and 8 at 198 fsw. Central venous bubbles were detected acoustically by means of a Doppler ultrasonic cuff surgically implanted around the inferior vena cava of each animal. Bubbles occurred from 20 to 60 min after the switch in both the 132 fsw and 198 fsw exposures, but were not always present in the 132 fsw exposure, and did not persist for as long. Bubbles or other Doppler events were often detected for the entire isobaric period-12 h-following the gas switch in the 198 fsw exposures. Decompressions were conducted according to the USN saturation tables and were uneventful, with only occasional bubbles. Supersaturation ratios calculated to have occurred for a considerable period after the gas switch were approximately 1.15 (tissue gas tension pi, divided by ambient hydrostatic pressure, P) with maxima at 1.26 for the faster tissues. These values are limiting ones in USN decompression only for the slower tissues. In general, therefore, these results argue for reducing the permissible ascent criteria for the faster tissues-assuming bubbles are to be avoided-and allowing more time at stops for non-saturation decompression. Gas switches from a more soluble to a less soluble and/or more rapidly diffusing gas should therefore be avoided until physiological limits are well worked out.

Transport phenomena in laminar flow of blood.

Recently it has been shown experimentally that transport of heat and gas (specifically oxygen and helium) are augmented in the laminar flow of aqueous suspensions of polystyrene spheres 50 and 150 micrometer in diameter. In this report, data on heat and gas transport are correlated. Application of this correlation to flowing blood leads to the following conclucions. There is no significant augmentation of oxygen and heat transport in flowing blood even at shear rates much higher than physiological shear rates; an observation which is in accord with the experimental results. The augmentation of the diffusion coefficient of plasma proteins in flowing blood, though not very high, appears to be measurable. Of the total measured augmentation of about 6000--30 000% in platelet diffusivity in flowing blood, quoted from the literature, about 500% is attributable from this correlation to fluid mechanical forces, and the balance is hypothetically attributed to other forces (electrical or biochemical) present in blood.

Transcutaneous blood gas measurement using a mass spectrometer.

We use a Perkin Elmer MGA 1100 mass spectrometer modified for blood gas tension measurements to study transcutaneous measurements of oxygen, carbon dioxide, nitrogen and helium in normal subjects. We use an aluminum sampling chamber heated to 42--44 degree C and connected to the mass spectrometer by about 2 m of stainless steel tubing. The sampling area of 5 cm2 is covered with a polytrifluorochloroethylene membrane 18 micrometer thick (Allied Chemical Co., Aclar 33c). The membrane is supported by sintered stainless steel disc with a thermistor incorporated for measurement of "membrane" temperature. The chamber is heated with a printed circuit heater (Minco) and is temperature regulated by a servo circuit. We have used the system to measure, O2, CO2 N2 and He via the heated skin in four normal subjects, breathing air and then 100% oxygen. We also observed the response to a single breath of helium. Helium appears at the skin within 10--15 sec. The time constant of its disappearance is about 70 sec. The average uncorrected gas tensions which we obtained breathing air were 11.2 kPa for oxygen, 5.1 kPa for carbon dioxide and 67.1 kPa for nitrogen. The corresponding values breathing oxygen were 41.1 kPa for oxygen, 4.4 kPa for carbon dioxide and 13.1 kPa for nitrogen.

Venous gas bubbles: production by transient, deep isobaric counterdiffusion of helium against nitrogen.

When awake goats were subjected to isobaric gas switching from saturation (17 hours) on 4.7 atmospheres of nitrogen (0.3 atmosphere of oxygen) to 4.7 atmospheres of helium (0.3 atmosphere of oxygen), bubbles detected by 5-megahertz Doppler ultrasound in the posterior vena cava 20 to 60 minutes after the switch continued for 4 hours. Similar experiments carried out at 6.7 atmospheres of inert gas and 0.3 atmosphere of oxygen produced more bubbles for as long as 12 hours after the gas switch. This is believed to be the first objective demonstration of the phenomenon of deep isobaric supersaturation under transient operational diving conditions at relatively shallow diving depths. Detection of bubbles by Doppler ultrasound confirms the potential importance of the phenomenon to shallow saturation diving and holds promise for better quantitification of its effects as well as those of its counterpart, isobaric undersaturation, which can confer a decompression advantage.