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.

Physical activity and functional abilities in adult males with haemophilia: a cross-sectional survey from a single US haemophilia treatment centre.

Physical activity and functional ability are important determinants of quality of life and these metrics are affected by both haemophilia and ageing. Outside haemophilic arthropathy, risk factors leading to reduced physical activity and function in people with haemophilia (PWH) are under-explored. The purpose of this analysis was to determine risk factors for reduced physical activity and functional limitations in PWH. A secondary analysis was conducted on data indexing physical activity and functioning of 88 PWH using data originally collected as part of a cross-sectional study at a single large haemophilia treatment centre. The Framingham Physical Activities Index (PAI), the Hemophilia Activities List (HAL) and the Timed Up-and-Go Test (TUG) were the outcome measures. The World Federation of Haemophilia (WFH) orthopaedic joint score was used as a measure of arthropathy. Multiple linear regression analysis was used to assess the relationship between the outcome measures and covariates. Worsening WFH joint score was independently associated with all three outcome measures (P < 0.05). Increasing age was associated with reduced PAI and increased TUG time (P < 0.05). The HAL summary score was decreased in patients with chronic liver disease (P = 0.006). The adjusted R(2) for each model was ≤ 0.35. This study provides evidence for the relationship between arthropathy and reduced physical functioning/activity, but also highlights that much of the variation in physical functioning/activity is not explained by haemophilia-related characteristics.

Dietary fat source alters hepatic gene expression profile and determines the type of liver pathology in rats overfed via total enteral nutrition.

To determine if dietary fat composition affects the progression of nonalcoholic fatty liver disease (NAFLD), we overfed male Sprague-Dawley rats low (5%) or high (70%) fat diets with different fat sources: olive oil (OO), corn oil (CO), or echium oil (EO), with total enteral nutrition (TEN) for 21 days. Overfeeding of the 5% CO or 5% EO diets resulted in less steatosis than 5% OO (P < 0.05). Affymetrix array analysis revealed significant differences in hepatic gene expression signatures associated with greater fatty acid synthesis, ChREBP, and SREBP-1c signaling and increased fatty acid transport (P < 0.05) in the 5% OO compared with 5% CO group. The OO groups had macrosteatosis, but no evidence of oxidative stress or necrosis. The 70% CO and 70% EO groups had a mixture of micro- and macrosteatosis or only microsteatosis, respectively; increased oxidative stress; and increased necrotic injury relative to their respective 5% groups (P < 0.05). Oxidative stress and necrosis correlated with increasing peroxidizability of the accumulated triglycerides. Affymetrix array analysis comparing the 70% OO and 70% CO groups revealed increased antioxidant pathways and lower expression of genes linked to inflammation and fibrosis in the 70% OO group. A second study in which 70% OO diet was overfed for 50 days produced no evidence of progression of injury beyond simple steatosis. These data suggest that dietary fat type strongly influences the progression of NAFLD and that a Mediterranean diet high in olive oil may reduce the risk of NAFLD progressing to nonalcoholic steatohepatitis.

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.

Mantle-circulation models with sequential data assimilation: inferring present-day mantle structure from plate-motion histories.

Data assimilation is an approach to studying geodynamic models consistent simultaneously with observables and the governing equations of mantle flow. Such an approach is essential in mantle circulation models, where we seek to constrain an unknown initial condition some time in the past, and thus cannot hope to use first-principles convection calculations to infer the flow history of the mantle. One of the most important observables for mantle-flow history comes from models of Mesozoic and Cenozoic plate motion that provide constraints not only on the surface velocity of the mantle but also on the evolution of internal mantle-buoyancy forces due to subducted oceanic slabs. Here we present five mantle circulation models with an assimilated plate-motion history spanning the past 120 Myr, a time period for which reliable plate-motion reconstructions are available. All models agree well with upper- and mid-mantle heterogeneity imaged by seismic tomography. A simple standard model of whole-mantle convection, including a factor 40 viscosity increase from the upper to the lower mantle and predominantly internal heat generation, reveals downwellings related to Farallon and Tethys subduction. Adding 35% bottom heating from the core has the predictable effect of producing prominent high-temperature anomalies and a strong thermal boundary layer at the base of the mantle. Significantly delaying mantle flow through the transition zone either by modelling the dynamic effects of an endothermic phase reaction or by including a steep, factor 100, viscosity rise from the upper to the lower mantle results in substantial transition-zone heterogeneity, enhanced by the effects of trench migration implicit in the assimilated plate-motion history. An expected result is the failure to account for heterogeneity structure in the deepest mantle below 1500 km, which is influenced by Jurassic plate motions and thus cannot be modelled from sequential assimilation of plate motion histories limited in age to the Cretaceous. This result implies that sequential assimilation of past plate-motion models is ineffective in studying the temporal evolution of core-mantle-boundary heterogeneity, and that a method for extrapolating present-day information backwards in time is required. For short time periods (of the order of perhaps a few tens of Myr) such a method exists in the form of crude 'backward' convection calculations. For longer time periods (of the order of a mantle overturn), a rigorous approach to extrapolating information back in time exists in the form of iterative nonlinear optimization methods that carry assimilated information into the past through the use of an adjoint mantle convection model.

Dynamic observation of pulmonary perfusion using continuous arterial spin-labeling in a pig model.

The continuous arterial spin-labeling (CASL) method of perfusion MRI is used to observe pulmonary perfusion dynamically in an animal model. Specifically, a respiratory-triggered implementation of the CASL method is used with approximate spatial resolution of 0.9 x 1.8 x 5.0 mm (0.008 cc) and 2-minute temporal resolution. Perfusion MRI is performed dynamically during repeated balloon occlusion of a segmental pulmonary artery, as well as during pharmacological stimulation. A total of three Yorkshire pigs were studied. The results demonstrate the ability of the endogenous spin-labeling method to characterize the dynamic changes in pulmonary perfusion that occur during important physiological alterations.

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.

Predicting response to regulatory change in the small group health insurance market: the case of association health plans and HealthMarts.

Lack of health insurance continues to be a concern for many people, even among those who are employed, and employees of small firms are much less likely to be insured than employees of larger firms. For several years, the U.S. Congress has considered legislation that would establish two new vehicles for offering health insurance coverage to small employers: association health plans (AHPs) and HealthMarts. In this paper, we present a model for estimating the impact the new entities would have on coverage and premiums in the small group health insurance market. The model produces a range of estimates based on assumptions, among others, about demand for insurance among small firms and their willingness to switch to less expensive, less generous benefit plans. We estimate that approximately 4.6 million people would obtain coverage through AHPs and HealthMarts, but fewer than half a million of them would be newly insured (based on 1999 population figures). Premiums would increase slightly for firms that continued to purchase coverage in the traditional market.

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.

Detection and localization of pulmonary air leaks using laser-polarized (3)He MRI.

Pulmonary air leaks were created in the lungs of Yorkshire pigs. Dynamic, 3D MRI of laser-polarized (3)He gas was then performed using a gradient-echo pulse sequence. Coronal magnitude images of the helium distribution were acquired during gas inhalation with a voxel resolution of approximately 1.2 x 2.5 x 8 mm, and a time resolution of 5 sec. In each animal, the ventilation images reveal focal high-signal intensity within the pleural cavity at the site of the air leaks. In addition, a wedge-shaped region of increased parenchymal signal intensity was observed adjacent to the site of the air leak in one animal. (3)He MRI may prove helpful in the management of patients with pulmonary air leaks.

Core cooling by central venous infusion of ice-cold (4 degrees C and 20 degrees C) fluid: isolation of core and peripheral thermal compartments.

BACKGROUND: Central venous infusion of cold fluid may be a useful method of inducing therapeutic hypothermia. The aim of this study was to quantify systemic heat balance and regional distribution of body heat during and after central infusion of cold fluid. METHODS: The authors studied nine volunteers, each on two separate days. Anesthesia was maintained with use of isoflurane, and on each day 40 ml/kg saline was infused centrally over 30 min. On one day, the fluid was 20 degrees C and on the other it was 4 degrees C. By use of a tympanic membrane probe core (trunk and head) temperature and heat content were evaluated. Peripheral compartment (arm and leg) temperature and heat content were estimated with use of fourth-order regressions and integration over volume from 18 intramuscular thermocouples, nine skin temperatures, and "deep" hand and foot temperature. Oxygen consumption and cutaneous heat flux estimated systemic heat balance. RESULTS: After 30-min infusion of 4 degrees C or 20 degrees C fluid, core temperature decreased 2.5 +/- 0.4 degrees C and 1.4 +/- 0.2 degrees C, respectively. This reduction in core temperature was 0.8 degrees C and 0.4 degrees C more than would be expected if the change in body heat content were distributed in proportion to body mass. Reduced core temperature resulted from three factors: (1) 10-20% because cutaneous heat loss exceeded metabolic heat production; (2) 50-55% from the systemic effects of the cold fluid per se; and (3) approximately 30% because the reduction in core heat content remained partially constrained to core tissues. The postinfusion period was associated with a rapid and spontaneous recovery of core temperature. This increase in core temperature was not associated with a peripheral-to-core redistribution of body heat because core temperature remained warmer than peripheral tissues even at the end of the infusion. Instead, it resulted from constraint of metabolic heat to the core thermal compartment. CONCLUSIONS: Central venous infusion of cold fluid decreases core temperature more than would be expected were the reduction in body heat content proportionately distributed. It thus appears to be an effective method of rapidly inducing therapeutic hypothermia. When the infusion is complete, there is a spontaneous partial recovery in core temperature that facilitates rewarming to normothermia.

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.

Providing health insurance to the short-term unemployed.

This paper assesses the likely effects of proposed federal programs to provide temporary subsidies to unemployed people for purchasing health insurance. A simulation model, using the Survey of Income and Program Participation and data from other sources, was used to quantify various effects of a typical proposal. The model illustrates how changing eligibility rules and subsidy formulas would alter the cost and other measures of program performance. If the plan were fully operational in 1998, about 1.1 million people (including insured dependents) would get at least a month of new insurance sometime during the year. The program would reduce the number of uninsured by less than half a million people.

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.

Constraints on the origin of the Moon's atmosphere from observations during a lunar eclipse.

The properties of the Moon's rarefied atmosphere, which can be traced through observations of sodium and potassium, provide important insights into the formation and maintenance of atmospheres on other primitive Solar System bodies. The lunar atmosphere is believed to be composed of atoms from the surface rocks and soil, which might have been sputtered by micrometeorites, by ions in the solar wind, or by photons. It might also form by the evaporation of atoms from the hot, illuminated surface. Here we report the detection of sodium emission from the Moon's atmosphere during a total lunar eclipse (which occurs when the Moon is full). The sodium atmosphere is considerably more extended at full Moon than expected--it extends to at least nine lunar radii--and its brightness distribution is incompatible with sources involving either solar-wind or micrometeorite sputtering. This leaves photon sputtering or thermal desorption as the preferred explanations for the lunar atmosphere, and suggests that sunlight might also be responsible for the transient atmospheres of other primitive bodies (such as Mercury).

All-sky Doppler interferometer for thermospheric dynamics studies.

An efficient, all-sky input optical system has been mated to a 100-mm-aperture Fabry-Perot interferometer that employs a cooled (-150 °C) CCD as a photon detector to create an all-sky Doppler interferometer. The instrument is capable of simultaneously measuring Doppler shifts and widths of nightglow emission lines from many different points in the sky, thereby providing determinations of upperatmosphere neutral wind and temperature fields over a large region (to ≈2000 km in extent). For OI 630-nm (thermosphere) and OH 799.6-nm (mesopause) nightglow emissions, exposure times of 5-15 min provide good-quality interferometric images. The capability of the all-sky Doppler interferometer is illustrated by examples of thermospheric wind and temperature fields measured over Millstone Hill, Massachusetts.