Comparisons of Noninvasive Methods Used to Assess Exercise Stroke Volume in Heart Failure with Preserved Ejection Fraction.

INTRODUCTION: Cardiopulmonary exercise testing (CPET) plays an important role in properly phenotyping signs and symptoms of heart failure with preserved ejection fraction (HFpEF). The prognostic value of CPET is strengthened when accompanied by cardiac hemodynamic measurements. Although recognized as the "gold" standard, cardiac catheterization is impractical for routine CPET. Thus, advancing the scientific/methodologic understanding of noninvasive techniques for exercise cardiac hemodynamic assessment is clinically impactful in HFpEF. This study tested the concurrent validity of noninvasive acetylene gas (C2H2) uptake, echocardiography (ECHO), and oxygen pulse (O2pulse) for measuring/predicting exercise stroke volume (SV) in HFpEF. METHODS: Eighteen white HFpEF and 18 age-/sex-matched healthy controls participated in upright CPET (ages, 69 ± 9 yr vs 63 ± 9 yr). At rest, 20 W, and peak exercise, SV was measured at steady-state via C2H2 rebreathe (SVACET) and ECHO (SVECHO), whereas O2pulse was derived (=V˙O2/HR). RESULTS: Resting relationships between SVACET and SVECHO, SVECHO and O2pulse, or SVACET and O2pulse were significant in HFpEF (R = 0.30, 0.36, 0.67), but not controls (R = 0.07, 0.01, 0.09), respectively. Resting relationships persisted to 20 W in HFpEF (R = 0.70, 0.53, 0.70) and controls (R = 0.05, 0.07, 0.21), respectively. Peak exercise relationships were significant in HFpEF (R = 0.62, 0.24, 0.64), but only for SVACET versus O2pulse in controls (R = 0.07, 0.04, 0.33), respectively. Standardized standard error of estimate between techniques was strongest in HFpEF at 20 W: SVACET versus SVECHO = 0.57 ± 0.22; SVECHO versus O2pulse = 0.71 ± 0.28; SVACET versus O2pulse = 0.56 ± 0.22. CONCLUSIONS: Constituting a clinically impactful step towards construct validation testing, these data suggest SVACET, SVECHO, and O2pulse demonstrate moderate-to-strong concurrent validity for measuring/predicting exercise SV in HFpEF.

An autopsy case of suicide by acetylene explosion: a case report.

We report an autopsy case of a male welder in his thirties who was found dead in an exploded truck cabin. The roof, windows and doors of the cabin had been blown up to 50 metres away. An oxygen cylinder and an acetylene cylinder, both unexploded, were found in the back of the truck. The deceased was lying on the driver's seat. His entire body was burnt, carbonised and partially skeletonised. There was a small amount of soot in his oesophagus and stomach and a large volume of bloody fluid in the trachea and bronchi. There was an extensive haemorrhage in the posterior thoracic wall. No drugs were detected in the blood. Hardly any carbon monoxide and combustion-related gases were detected in the blood, therefore he was not considered to have died from the fire. Acetylene was detected in his blood (21.5 microg/ml in the femoral vein blood) and urine (7.49 microg/ml), with marked haemorrhaging in his back. We therefore concluded that the victim died because of an acetylene explosion in the cabin and also that this was a suicide.

Analysis of acetylene in blood and urine using cryogenic gas chromatography-mass spectrometry.

A method for quantitative analysis of acetylene in blood and urine samples was investigated. Using cryogenic gas chromatography-mass spectrometry (GC-MS), acetylene was measured with isobutane as the internal standard in the headspace method, which revealed a linear response over the entire composite range with an excellent correlation coefficient, both in blood (R = 0.9968, range = 5.39-43.1 microg/ml) and urine (R = 0.9972, range = 2.16-10.8 microg/ml). The coefficients of variation (CV) for blood ranged from 2.62 to 11.6% for intra-day and 4.55 to 10.4% for inter-day. The CV for urine ranged from 2.38 to 3.10% for intra-day and 4.83 to 11.0% for inter-day. The recovery rate as an index of accuracy ranged from 83 to 111%. The present method showed good reliability, and is also simple and rapid. In actual samples from a charred cadaver due to acetylene explosion, the measured concentrations of acetylene by this method were 21.5 microg/ml for femoral vein blood, 17.9 microg/ml for right atrial blood, 25.5 microg/ml for left atrial blood and 7.49 microg/ml for urine. Quantification of acetylene provides important information, because the acetylene concentration is a vital reaction or sign. For example, when acetylene is filled in a closed space and then explodes, in antemortem explosion, the blood acetylene concentration of the cadaver might be significant. On the other hand, in postmortem explosion, acetylene is not detected in blood. Furthermore, when several victims are involved in one explosion, comparison of the sample concentrations can also provide useful information to establish the conditions at the accident scene; therefore, the present method is useful in forensics.

Noninvasive measurement of cardiac output by an acetylene uptake technique and simultaneous comparison with thermodilution in ICU patients.

A simple, accurate, and noninvasive method of cardiac output measurement can be an extremely useful tool for the clinician and researcher. This study used the acetylene gas uptake technique to measure the absorption of acetylene into the pulmonary circulation during a constant exhalation, which is proportional to the pulmonary capillary blood flow and to the cardiac output, assuming no anatomic shunts. We compared cardiac output measured simultaneously by this and by the standard thermodilution (TD) technique in 21 patients in the ICU with a variety of medical and surgical conditions and a wide range of cardiac outputs. We also compared the two techniques in 19 ambulatory patients with a 2-h interval between the invasive and noninvasive test to assess variability over time. The two tests had an excellent correlation when done simultaneously with a correlation coefficient of 0.89 (p < 0.001). With a 2-h interval between the two tests, the correlation coefficient was 0.66 (p = 0.0018). Nine patients in the simultaneous group had cardiomyopathy. When they were excluded, the correlation coefficient increased to 0.96. Most of these patients had documented tricuspid regurgitation (TR), which may underlie the greater difference between acetylene uptake and TD values, with consistently higher TD values in these patients. This study confirms the correlation between the acetylene uptake and the standard invasive TD techniques in sick patients with various medical and surgical conditions and a wide range of cardiac outputs. Furthermore, we believe this would be a more accurate method for measuring cardiac output in patients with cardiomyopathy and TR because it is based only on pulmonary capillary blood flow.

In vivo quantitation of carbonic anhydrase and band 3 protein contributions to pulmonary gas exchange.

The contributions to pulmonary gas exchange of red blood cell (RBC) membrane band 3 protein HCO3(-)-Cl- exchange and carbonic anhydrase- (CA) catalyzed HCO3- dehydration have never been determined directly in the whole animal. We utilized an experimental and model approach to measure these by analysis of phase III exhaled CO2 and O2 profiles in anesthetized dogs. In this method, we inhibit RBC membrane band 3 protein and cytoplasmic CA in RBCs passing the pulmonary capillaries and lung vascular luminal membrane-bound CA during a single ventilatory cycle. This is achieved with appropriately timed right atrial infusions of 4,4'-dinitrostilbene-2,2'-disulfonate (DNDS) to inhibit band 3 protein, ethoxzolamide (a lipophilic CA inhibitor with rapid membrane penetrance) to inhibit RBC and lung tissue CA, and benzolamide (an extremely hydrophilic CA inhibitor with virtually no penetrance into RBC cytoplasm) to inhibit only lung vascular luminal membrane CA. DNDS caused a 15% reduction in CO2 production (VCO2) without any change in O2 consumption (VO2). The addition of benzolamide to DNDS did not cause any further decrease in VCO2. Inhibition of RBC CA by ethoxzolamide caused a 67% reduction in VCO2 and a 11.5% reduction in VO2. Inhibition of lung vascular CA by benzolamide alone caused no statistically significant changes in either VCO2 or VO2. These results are in general agreement with in vitro data and model calculations. The only exceptions are the higher than predicted effect of RBC CA inhibition on VO2 (Bohr effect) and the lack of any contribution to CO2 transfer in the dog by lung vascular CA with access to plasma as a possible consequence of an endogenous plasma CA inhibitor.

Measurement of cardiac output by automated single-breath technique, and comparison with thermodilution and Fick methods in patients with cardiac disease.

Accurate noninvasive methods are needed for determination of cardiac output. Current methods are generally complex or may be unreliable. A previously described method, based on absorption of acetylene gas during a constant exhalation that enables calculation of cardiac output by estimating pulmonary capillary circulation, is incorporated in a new, automated commercial product (SensorMedics 2200). In this study, cardiac output by single-breath acetylene blood flow measured with this device was compared with the standard thermodilution and direct Fick methods in 20 patients undergoing cardiac or pulmonary artery catheterization. Patients inhaled test gas mixture to total lung capacity and exhaled at a constant rate through an adjustable resistor. Lung volumes and noninvasive acetylene blood flow value were calculated automatically. Correlation between the automated single-breath technique and both thermodilution and Fick cardiac output determinations was very high (correlation coefficients were 0.90 and 0.92, respectively), regression slopes were close to identity (0.98 and 0.90), and bias (-0.39 and -0.79 liter/min) and precision (0.94 and 1.02) were good; when shunt correction was applied, bias was reduced to 0.06 and 0.35 liter/min, respectively. Rapid, accurate, noninvasive measurement of cardiac output was easily obtained using the automated device. This technique may have a wide applicability for noninvasive evaluation of patients with cardiac disease and for monitoring effects of therapeutic interventions.

Effects of environmental O2 on blood flow and diffusing capacity in amphibian skin.

The effects of local environmental PO2 on cutaneous blood flow (Q) and the membrane diffusing capacity of the skin (D) were investigated in the leopard frog, Rana pipiens, and the lungless salamander, Desmognathus quadramaculatus. Halothane anesthetized animals were equilibrated with Freon-22 (Fr) and acetylene (Ac) in a box. A gas mixture containing either 0, 20 or 40% O2, respectively, in N2 and initially free of Fr and Ac was drawn through a small sample chamber on the abdomen. The excretion of Fr and Ac into the chamber was analyzed with a mass spectrometer. These conditions allowed the determination of the cutaneous conductance to Fr (GFr) and Ac (GAc) at the 3 levels of local environmental O2. GFr and GAc of the isolated skin and the blood solubilities of the 2 gases were also determined. To estimate Q, DAc and DFr, the data were analyzed with a homogeneous single capillary model. In the frog, Q varied directly with sample chamber [O2], but chamber [O2] had no effect on D. In the salamander, O2 had no effect on either Q or D. The results indicate that regulation of cutaneous gas exchange in the frog by local environmental O2 only involves alterations in Q. Similar control of cutaneous gas exchange is absent in the lungless salamander.

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 hematocrit and temperature on solubility of acetylene and dimethyl ether.

Estimation of pulmonary capillary blood flow (Qc) and tissue volume (Vt) by rebreathing acetylene (Ac) and dimethyl ether (DME) is dependent on the blood-gas partition coefficient (lambda) of these gases. We investigated the effects of hematocrit (Hct) and temperature on lambda. Human and canine blood was equilibrated at different Hct for 40 min at 37.5 degrees C with 1% Ac and 1% DME in air. Gas concentration in the headspace was measured by gas chromatography. lambda Ac increased with increasing Hct, suggesting a slight lipid affinity, whereas lambda DME decreased with increasing Hct, displaying the known blood-water content dependence. The influence of temperature on lambda in the range of 32--47 degrees C was investigated also. lambda Ac and lambda DME decreased as the temperature was raised, in accordance with the Gibbs-Helm-holtz equation. Empirical equations were derived to relate lambda to to Hct and temperature.

Solubility of acetylene in human blood determined by mass spectrometry.

To measure the acetylene solubility (alpha C2H2) in human blood, a blood sample, which had been equilibrated with a gas mixture containing C2H2, was injected into an airtight acetylene-free vessel, and the gas partial pressure was measured by mass spectrometry after reequilibration. The system was calibrated by injecting into the vessel a known volume of the equilibrating gas mixture. At 37 degrees C, alpha C2H2 averaged 0.768 +/- 0.004 (SD) ml STPD.ml blood-1.atm-1, which is only slightly above the data from the literature.

Cardiac output determination by simple one-step rebreathing technique.

We have developed a rebreathing technique for measuring cardiac output in resting or exercising subjects. The data needed are the subject's CO2 dissociation curve, the initial volume and CO2 fraction of the rebreathing bag, and a record of CO2 at the mouth during the maneuver. From these one can obtain all the values required to solve the Fick equation. The combined error due to inaccuracy in reading the tracings and to the simplifying assumptions was found to be small (mean = 0.5%, SD ;.5%). Cardiac output values determined with this technique in normal subjects were on the average 2% higher than those obtained simultaneously with an acetylene rebreathing method (n = 49, SD = 11%). Among the advantages of the technique are that it requires analysis of a single gas, takes less than thirty seconds per determination, allows one to obtain repeated measurements at rapid intervals, is not affected by the ability of lung tissue to store CO2, and eliminates many of the assumptions usually made in non-invasive measurements of cardiac output.