Ventilation/perfusion ratios measured by multiple inert gas elimination during experimental cardiopulmonary resuscitation.

BACKGROUND: During cardiopulmonary resuscitation (CPR) the ventilation/perfusion distribution (VA /Q) within the lung is difficult to assess. This experimental study examines the capability of multiple inert gas elimination (MIGET) to determine VA /Q under CPR conditions in a pig model. METHODS: Twenty-one anaesthetised pigs were randomised to three fractions of inspired oxygen (1.0, 0.7 or 0.21). VA/ Q by micropore membrane inlet mass spectrometry-derived MIGET was determined at baseline and during CPR following induction of ventricular fibrillation. Haemodynamics, blood gases, ventilation distribution by electrical impedance tomography and return of spontaneous circulation were assessed. Intergroup differences were analysed by non-parametric testing. RESULTS: MIGET measurements were feasible in all animals with an excellent correlation of measured and predicted arterial oxygen partial pressure (R(2) = 0.96, n = 21 for baseline; R(2) = 0.82, n = 21 for CPR). CPR induces a significant shift from normal VA /Q ratios to the high VA /Q range. Electrical impedance tomography indicates a dorsal to ventral shift of the ventilation distribution. Diverging pulmonary shunt fractions induced by the three inspired oxygen levels considerably increased during CPR and were traceable by MIGET, while 100% oxygen most negatively influenced the VA /Q. Return of spontaneous circulation were achieved in 52% of the animals. CONCLUSIONS: VA /Q assessment by MIGET is feasible during CPR and provides a novel tool for experimental purposes. Changes in VA /Q caused by different oxygen fractions are traceable during CPR. Beyond pulmonary perfusion deficits, these data imply an influence of the inspired oxygen level on VA /Q. Higher oxygen levels significantly increase shunt fractions and impair the normal VA /Q ratio.

Mechanical ventilator for delivery of ¹7O2 in brief pulses.

The ¹7O nucleus has been used recently by several groups for magnetic resonance (MR) imaging of cerebral metabolism. Inhalational delivery of ¹7O(2) in very brief pulses could, in theory, have significant advantages for determination of the cerebral metabolic rate for oxygen (CMRO2) with MR imaging. Mechanical ventilators, however, are not typically capable of creating step changes in gas concentration at the airway. We designed a ventilator for large animal and human studies that provides mechanical ventilation to a subject inside an MR scanner through 25 feet of small-bore connecting tubing, and tested its capabilities using helium as a surrogate for ¹7O2. After switching the source gas from oxygen to helium, the 0-90% response time for helium concentration changes at the airway was 2.4 seconds. The capability for creating rapid step changes in gas concentration at the airway in large animal and human studies should facilitate the experimental testing of the delivery ¹7O2 in brief pulses, and its potential use in imaging CMRO2.

[Ventilation-perfusion distributions in the lungs. A novel technique for rapid measurement]. / Ventilations-Perfusions-Verteilungen in der Lunge. Eine neue Technik zur schnellen Bestimmung.

The multiple inert gas elimination technique (MIGET) represents the gold standard for analysis of ventilation and perfusion distributions in the lung. Modification of this technique allows a much simpler sample processing and hence permits routine clinical application of this technique. MIGET using micropore membrane inlet mass spectrometry (MMIMS) might, therefore, facilitate early diagnosis of lung diseases and monitoring of therapeutic interventions in the future.

Phase diagram of superfluid 3He in 99.3% porosity aerogel.

We report on continuous-wave NMR measurements of the energy gaps of the A-like and B-like superfluid phases of 3He at 28.4 mT confined to a 99.3% porosity silica aerogel. The gaps are suppressed by the presence of the aerogel in a temperature-independent manner, but the suppression is considerably stronger than expected from the suppression of T(c). We then use our measurements to calculate the free energy ratio between the A-like and B-like phases. The equilibrium AB transition temperature, derived from where this ratio reaches unity, is consistent with previous measurements of the initial displacement of the pinned AB interface on warming. On this basis, we present for the first time the equilibrium phase diagram of the A-like and B-like phases of superfluid 3He in aerogel.

Interfacial pinning in the superfluid 3He A-B transition in aerogel.

Continuous-wave NMR studies of 3He in the presence of 99.3% porosity silica aerogel at 34.0 bars and in a magnetic field of 28.4 mT reveal a first-order phase transition between A-like and B-like superfluid phases on both warming and cooling. NMR spectra show that the phases on warming are the same as the phases on cooling, and the interface between them is found to be strongly pinned, even close to T(c,aero). The observed behavior is consistent with spatial variation of pinning strengths within the aerogel.

Effect of culture PO2 on macrophage (RAW 264.7) nitric oxide production.

Macrophages are commonly cultured at a PO2 of 149 Torr, but tissue macrophages in vivo live in an environment of much lower oxygen tension. Despite the many potential mechanisms for changes in oxygen tension to influence nitric oxide (NO) synthesis, there have been few reports investigating the effect of PO2 on macrophage NO production. With the use of a culture chamber designed to rigorously control oxygen tension, we investigated the effects of culture PO2 on macrophage NO production, inducible nitric oxide synthase (iNOS) activity, iNOS protein, and tumor necrosis factor production. NO production and iNOS activity were linearly related in the range of 39.4 to 677 Torr, but not in the range of 1.03 to 39.4 Torr. Therefore, results obtained in vitro for the high oxygen tensions commonly used in cell culture were quantitatively and qualitatively different from results obtained in cells cultured at the lower oxygen tensions that more accurately reflect the in vivo environment. The influence of oxygen tension on NO production has implications for cell culture methodology and for the relationship between microcirculatory dysfunction and inflammatory responses in rodent models of sepsis.

Sequential V(A)/Q distributions in the normal rabbit by micropore membrane inlet mass spectrometry.

We developed micropore membrane inlet mass spectrometer (MMIMS) probes to rapidly measure inert-gas partial pressures in small blood samples. The mass spectrometer output was linearly related to inert-gas partial pressure (r(2) of 0.996-1.000) and was nearly independent of large variations in inert-gas solubility in liquid samples. We infused six inert gases into five pentobarbital-anesthetized New Zealand rabbits and used the MMIMS system to measure inert-gas partial pressures in systemic and pulmonary arterial blood and in mixed expired gas samples. The retention and excretion data were transformed into distributions of ventilation-to-perfusion ratios (V(A)/Q) with the use of linear regression techniques. Distributions of V(A)/Q were unimodal and broad, consistent with prior reports in the normal rabbit. Total blood sample volume for each VA/Q distribution was 4 ml, and analysis time was 8 min. MMIMS provides a convenient method to perform the multiple inert-gas elimination technique rapidly and with small blood sample volumes.

The effectiveness of rapidly infused intravenous fluids for inducing moderate hypothermia in neurosurgical patients.

UNLABELLED: Moderate hypothermia is often used for cerebral protection during anesthesia for cerebral aneurysm clipping. No reliable, rapid, and practical noncardiopulmonary bypass methods for the induction of hypothermia to core temperatures <34 degrees C have been reported. We assessed the effects of IV administration of chilled 5% albumin (5 mL/kg at 1-6 degrees C) on core temperature after surface cooling to approximately 34 degrees C. We calculated thermal distribution volume from the change in core temperature after the chilled fluid infusions. We also compared rapid administration (5 mL/kg over 30 min) with very rapid administration (5 mL/kg over 3-5 min). Chilled albumin 5 mL/kg infused over 5 min reduced core temperature by 0.6+/-0.1 degrees C. The same volume of chilled albumin infused over 30 min reduced core temperature by 0.4+/-0.1 degrees C. The calculated thermal distribution volume was less than one third of total body volume. Because the thermal distribution volume in these hypothermic patients was much lower than total body volume, the chilled IV fluids in this study were 3 times more effective in inducing hypothermia than suggested by a simple calculation. To achieve maximal effectiveness, however, chilled fluids must be administered very rapidly (>100 mL/min) to avoid heat gains in standard IV tubing that occur even with rapid administration. IMPLICATIONS: Chilled IV fluids can be much more effective for the induction of hypothermia than commonly assumed, but they must be administered very rapidly to avoid heat gains in IV tubing.

Countercurrent extraction of sparingly soluble gases for membrane introduction mass spectrometry.

Membrane introduction mass spectrometry has been applied to inert gas measurements in blood and tissue, but gases with low blood solubility are associated with reduced sensitivity. Countercurrent extraction of inert gases from a blood sample into a water carrier phase has the potential to extract most of the gas sample while avoiding dependence of signal on blood solubility. We present the design of a membrane countercurrent exchange (CCE) device coupled with a conventional direct insertion membrane probe to measure partial pressure of low solubility inert gases in aqueous samples. A mathematical model of steady-state membrane CCB predicts that countercurrent extraction with appropriate selection of carrier and sample flow rates can provide a mass spectrometer signal nearly independent of variations in solubility over a specified range, while retaining a linear response to changes in gas partial pressure over several orders of magnitude. Experimental data are presented for sulfur hexafluoride and krypton in water samples. Optimal performance is dependent on adequate equilibration between the sample and carrier streams, and the large resistance to diffusion in the aqueous phase for insoluble gases presents a substantial challenge to the application of this principle.

The importance of a source term in modeling multibreath inert gas washout.

The single path model (SPM) of airway gas transport with a distributed blood source term was used to simulate multiple breath inert lung gas washout of N2, He, and SF6 after total body equilibration with these gases. Normalized phase III inert gas washout slopes were computed for each breath and compared with published experimental data obtained under similar conditions on human subjects. The model predicts a normalized slope asymptote which agrees with experimental results within two standard deviations or less of the mean, depending on the lengths and diameters assumed in the acinar airways of the SPM. In the model and in the human subject data, the asymptote represents the development of a quasi-steady state in which the volume of inert gas exhaled at the mouth is equal to the volume transported into the acinar airways by the pulmonary blood during each breath. The present study indicates that at least in the steady state, airway inhomogeneity is not essential to model lung washout data, and that a distributed blood source term in the SPM yields good agreement with experiment.

Noninvasive recovery of acinar anatomic information from CO2 expirograms.

A numerical single path model of respiratory gas exchange with distributed alveolar gas sources was used to estimate the anatomical changes in small peripheral airways such as occur in chronic obstructive pulmonary diseases (COPD). A previous sensitivity analysis of the single path model showed that decreasing total acinar airway cross-sectional area by an area reduction factor, R, results in computed gas expirograms with Phase III steepening similar to that observed in COPD patients. From experimental steady state CO2 washout data recorded from six healthy subjects and six COPD patients, optimized area reduction factors for the single path model were found that characterize peripheral airway anatomy for each subject. Area reduction factors were then combined with measured functional residual capacity data to calculate the normalized peripheral airspace diameters in a given subject, relative to the airspace diameters in the generations of an idealized standard lung. Mean area reduction factors for the patient subgroup were 63% of those for the healthy subgroup, which is related to the gas transport limitation observed in disease. Mean airspace sizes for the patient subgroup were 235% of the healthy subgroup, which characterizes the increase in size and reduction in number of peripheral airspaces due to tissue erosion in emphysema. From these results, the air-phase diffusive conductance in COPD patients was calculated to be 32% of the mean value in the healthy subjects. These findings correlated well with standard pulmonary function test data for the patients and yield the recovery of acinar airway information from gas washout by combining the single path model with experimental measurements.

Modelling steady state pulmonary elimination of He, SF6 and CO2: effect of morphometry.

We studied the influence of acinar morphometry on the shape of simulated expirograms computed from a single path convection-diffusion model that includes a source term for gas evolution from the blood (Scherer et al., J. Appl. Physiol. 64: 1022-1029, 1988). Acinar structure was obtained from published data of 3 different lung morphometries. The simulations were performed over a range of tidal volumes (VT) and breathing frequencies (f) comparable to those observed in a previously reported human study. Airways dead space (VDaw) increased with VT in all the morphometric models tested and in the experimental data. The increase in VDaw with VT was inversely related to the diffusivity of the evolving gas and to the rate of increase in airway cross-section of the most mouthward (proximal) alveolated generations of the models. Normalized phase III slope for all the gases decreased with increasing VT in all the models as was previously reported for healthy human subjects. In the model simulations, the greatest sensitivity of phase III slope to VT was seen with the least diffusible gas using the airway morphometry with the smallest cross-sectional areas in the proximal alveolated generations. We conclude that both VDaw and phase III slope of an evolving gas are sensitive to the geometry of the proximal acinar airways and that this is manifest by their dependence on tidal volume, breathing frequency, molecular diffusivity and alveolar/blood source emission rate. The model simulations indicate that heterogeneity of gas washout is not required to explain the magnitude of the phase III slope in healthy human subjects.

Diffusivity, respiratory rate and tidal volume influence inert gas expirograms.

We modified, and developed software for, a computer-controlled quadrupole mass spectrometer to measure complete breath-by-breath expirograms of helium (He) and sulfur hexafluoride (SF6) exhaled during the infusion of saline saturated with the inert gases. He and SF6 have similar blood solubilities but very different gas phase diffusivities allowing examination of the influence of gas phase diffusivity on steady state inert gas expirograms. We studied six normal human volunteers in nine separate studies and examined the influence of tidal volume (VT) and breathing frequency (f) on the airways dead space (VDaw) and alveolar plateau slope (phase III) for the inert gases and CO2. The experimental data showed a reduction in VDaw with rapid shallow breathing, while phase III slope increased by a factor of two to three. We critically evaluated the data and methodology of these and previously reported studies of continuous and single breath washout of He and SF6. In general the 15 to 20 ml differences in VDaw between He and SF6 were in keeping with previous studies by others. The ratio of phase III slopes of SF6 to He reported by us previously (Scherer et al., J. Appl. Physiol. 64: 1022-1029, 1988) was 3.13. In the current study, which includes the analysis of more than 400 He and SF6 breaths, the ratio of SF6 to He slope was 1.85. The difference between the two studies was largely related to the improved methodology of the current study, particularly for the measurement of He. The results support the conclusion that diffusivity is an important component of both phase II and phase III of the expirogram. However, the difference in phase III between He and SF6 is somewhat less than previously reported.

Skin blood flow from gas transport: helium xenon and laser Doppler compared.

A study was designed to compare three independent measures of cutaneous blood flow in normal healthy volunteers: xenon-133 washout, helium flux, and laser velocimetry. All measurements were confined to the volar aspect of the forearm. In a large group of subjects we found that helium flux through intact skin changes nonlinearly with the controlled local skin temperature whereas helium flux through stripped skin, which is directly proportional to skin blood flow, changes linearly with cutaneous temperature over the range 33 degrees to 42 degrees. In a second group of six volunteers we compared helium flux through stripped skin to xenon-133 washout (intact skin) at a skin temperature of 33 degrees, and we found an essentially linear relationship between helium flux and xenon measured blood flow. In a third group of subjects we compared helium flux blood flow (stripped skin) to laser doppler velocimetric (LDV) measurements (intact skin) at adjacent skin sites and found a nonlinear increase in the LDV skin blood flow compared to that determined by helium over the same temperature range. A possible explanation for the nonlinear increases of helium flux through intact skin and of LDV output with increasing local skin temperature is that they reflect more than a change in blood flow. They may also reflect physical changes in the stratum corneum, which alters its diffusional resistance to gas flux and its optical characteristics.

Numerical and experimental study of steady-state CO2 and inert gas washout.

The predictions of a single-path trumpet-bell numerical model of steady-state CO2 and infused He and sulfur hexafluoride (SF6) washout were compared with experimental measurements on healthy human volunteers. The mathematical model used was a numerical solution of the classic airway convention-diffusion equation with the addition of a distributed source term at the alveolar end. In the human studies, a static sampling technique was used to measure the exhaled concentrations and phase III slopes of CO2, He, and SF6 during the intravenous infusion of saline saturated with a mixture of the two inert gases. We found good agreement between the experimentally determined normalized slopes (phase III slope divided by mixed expired concentration) and the numerically determined normalized slopes in the model with no free parameters other than the physiological ones of upper airway dead space, tidal volume, breathing frequency, and breathing pattern (sinusoidal). We conclude 1) that the single-path (Weibel) trumpet-bell anatomic model used in conjunction with the airway convection-diffusion equation with a distributed source term is adequate to describe the steady-state lung washout of CO2 and infused He and SF6 in normal lungs and 2) that the interfacial area separating the tidal volume fron from the functional residual capacity gas, through which gas diffusion into the moving tidal volume occurs, exerts a major effect on the normalized slopes of phase III.

Gas flux through human skin: effect of temperature, stripping, and inspired tension.

The flux of He and O2 through intact adult human skin was measured at various inspired concentrations and skin temperatures. The skin surface was then stripped with cellophane tape to alter the diffusional conductance of the stratum corneum. He flux for stripped skin was used to estimate skin perfusion as a function of local temperature, and diffusional conductance for O2 was estimated from O2 flux and perfusion. The flux of He or O2 at constant skin temperature can be related to inspired concentration by a simple linear model. Increasing surface temperature in the range 33-43 degrees C produced a much larger increase in O2 flux than in He flux for intact skin. Skin stripping greatly increased skin O2 flux. Estimated skin conductance for O2 showed a more marked temperature dependence than estimated skin perfusion. The results suggest that raising skin temperature in the range 38-43 degrees C has only a modest effect on skin perfusion and that stratum corneum conductance may have a major role in the large increase of O2 flux with temperature.