In this study we determined reference values of total diffusing capacity of carbon monoxide (DLCO) and DLCO per liter alveolar volume (DLCO/VA) at total lung capacity (TLC) and at lung volumes below TLC in sitting position. In 55 healthy nonsmoking volunteers (20-85 yr old), we determined reference values at TLC level in which age was the only parameter. In a subgroup (n = 16) these references did not change by correction for normal variability in hemoglobin concentration. In all volunteers DLCO decreased and DLCO/VA increased with decreasing VA. The increase in DLCO/VA was linear and less in older subjects. We derived equations to calculate reference values of DLCO/VA for lung volumes at and below TLC with two methods: 1) "random coefficients linear" model, which calculates the reference values directly, and 2) a conversion method, which calculates DLCO/VA for lower VA levels from reference values at TLC. An advantage of the conversion method is the suitability of DLCO/VA reference values at TLC of other populations. A disadvantage is the greater standard deviation of these reference values compared with those obtained by the random coefficients linear method. DLCO can be found by multiplying DLCO/VA with VA.

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Normal subjects have a larger diffusing capacity normalized per liter alveolar volume (DL/VA) in the supine than in the sitting position. Body position changes total lung diffusing capacity (DL), DL/VA, membrane conductance (Dm), and effective pulmonary capillary blood volume (Qc) as a function of alveolar volume (VA). These functions were studied in 37 healthy volunteers. DL/VA vs. VA yields a linear relationship in sitting as well as in supine position. Both have a negative slope but usually do not run parallel. In normal subjects up to 50 yr old DL/VA and DL increased significantly when subjects moved from a sitting to a supine posture at volumes between 50 and 100% of total lung capacity (TLC). In subjects greater than 50 yr old the responses of DL/VA and DL to change in body position were not significant at TLC. Functional residual capacity (FRC) decreases and DL/VA increases in all normal subjects when they change position from sitting to supine. When DL/VA increases more than predicted from the DL/VA vs. VA relationship in a sitting position, we may infer an increase in effective Qc in the supine position. In 56% of the volunteers, supine DL was smaller than sitting DL despite a higher DL/VA at FRC in the supine position because of the relatively larger decrease in FRC. When the positional response at TLC is studied, an estimation obtained accidentally at a volume lower than TLC may influence results. Above 80% of TLC, Dm decreased significantly from sitting to supine. Below this lung volume the decrease was not significant. The relationship between Qc and VA was best described by a second-order polynomial characterized by a maximum Qc at a VA greater than 60% of TLC. Qc was significantly higher in the supine position than in the sitting position, but the difference became smaller with increasing age. In observing the sitting and supine positions, we saw a decrease in maximum Qc normalized per square meter of body surface area with age.

The reliability of cardiac output estimation by thermodilution during artificial ventilation was studied in anesthetized pigs at the right side of the heart. The estimates exhibited a cyclic modulation related to the ventilation. The amplitude of the modulation was independent of the level of positive end-expiratory pressure, ventilatory pattern and volemic loading of the animals. However, a non-constant phase relation existed between the ventilatory cycle and the modulation. Single observations at a fixed moment in the ventilatory cycle are therefore not appropriate for estimation of mean cardiac output nor for studying its relative changes. The averaging of estimates spread equally over the ventilatory cycle led to a much larger reduction in the deviation of the averages from the mean cardiac output than an averaging procedure of randomly selected estimates. The accuracy of estimation of mean cardiac output by two estimates equally spread in the ventilatory cycle was equal to the accuracy obtained by averaging five randomly selected estimates. Averaging four estimates, equally spread in the cycle, appeared to be the optimal procedure. For 89% of all averages an accuracy of 5% around the mean was obtained and for 99% an accuracy of +/- 10%.

Abstract. The application of the thermodilution method in conditions associated with variations in blood flow implies a misuse of the Stewart Hamilton equation. Therefore, we studied the reliability of the thermodilution method for the estimation of mean cardiac output (CO) during mechanical ventilation in patients (n = 9). Variation of the injection moment in the ventilatory cycle elicited a cyclic variation of CO estimates. This variation was not the same for all patients neither in phase nor in amplitude. Therefore, no specific phase in the ventilatory cycle could be selected for an accurate estimation of mean CO. Averaging CO estimates randomly distributed in the venfilatory cycle led to an improvement of accuracy with the square root of the number of observations. The averaging of CO estimates spread equally over the ventilatory cycle led to a much better result, e.g., the variation in the average of two estimates equally spread in the ventilatory cycle was similar to the variation in the average of four random estimates. We conclude that averaging of 3 or 4 estimates spread equally over the ventilatory cycle is an adequate strategy to estimate mean cardiac output in patients reliably. Key words: Cardiac output -Mechanical ventilationMultiple injections -ThermodilutionFor an accurate estimation of mean cardiac output using the thermodilution method several conditions have to be fulfilled: (i) no loss of indicator, (ii) complete mixing of indicator and blood, (iii) a constant bloodflow, and (iv) a constant baseline temperature. Under these conditions the Stewart-Hamilton equation, as incorporated in many commercial cardiac output computers, can be used. During mechanical ventilation, when bloodflow is modulated by cyclic changes in intra-thoracic pressure [1,2], the Stewart-Hamilton equation is misused. In practice this may lead to a considerable scatter in random estimates of cardiac output even when the measurements are performed during otherwise haemodynamically stable conditions. These cardiac output values are dependent on the moment of injection of indicator in the ventilatory cycle, in pigs [3][4][5], dogs [6,7], and men [8,9].Recommendations for an accurate estimation of mean cardiac output during mechanical ventilation are contradictory. Stevens et al. [9] recommended multiple injections at the end of expiration, whereas Okamoto et al. [8] recommended paired measurements at mid-inspiration and mid-expiration. From our animal studies [3][4][5] we concluded that mean cardiac output could be estimated accurately by calculating the averaged value of four measurements equally spread over the ventilatory cycle. Schneider and Powner [7] confirmed this conclusion in dogs and in one patient.The objective of the present clinical study was to evaluate the errors in the thermodilution cardiac output estimates during mechanical ventilation in patients in order to find an adequate strategy for a reliable estimation of mean cardiac output. MethodsNine male patients aged 55 to 67 years were studied after coronary a...

The metabolic properties and ultrastructure of mesophilic aggregates from a full-scale expanded granular sludge bed reactor treating brewery wastewater are described. The aggregates had a very high methanogenic activity on acetate (17.19 mmol of CH 4 /g of volatile suspended solids [VSS]⅐day or 1.1 g of CH 4 chemical oxygen demand/g of VSS⅐day). Fluorescent in situ hybridization using 16S rRNA probes of crushed granules showed that 70 and 30% of the cells belonged to the archaebacterial and eubacterial domains, respectively. The spherical aggregates were black but contained numerous whitish spots on their surfaces. Cross-sectioning these aggregates revealed that the white spots appeared to be white clusters embedded in a black matrix. The white clusters were found to develop simultaneously with the increase in diameter. Energy-dispersed X-ray analysis and back-scattered electron microscopy showed that the whitish clusters contained mainly organic matter and no inorganic calcium precipitates. The white clusters had a higher density than the black matrix, as evidenced by the denser cell arrangement observed by high-magnification electron microscopy and the significantly higher effective diffusion coefficient determined by nuclear magnetic resonance imaging. Highmagnification electron microscopy indicated a segregation of acetate-utilizing methanogens (Methanosaeta spp.) in the white clusters from syntrophic species and hydrogenotrophic methanogens (Methanobacterium-like and Methanospirillum-like organisms) in the black matrix. A number of physical and microbial ecology reasons for the observed structure are proposed, including the advantage of segregation for high-rate degradation of syntrophic substrates.The view of the structure of biofilms has dramatically changed during the last decade. Until the early 1990s, biofilms were considered more or less homogeneous layers of microorganisms embedded in a matrix of extracellular polymeric substances (23, 32). The application of one-dimensional models to calculate concentration profiles in these biofilms is straightforward. In general, an excellent agreement between observed concentration gradients (16) and predicted ones was obtained using one-dimensional models (34) for the biofilm systems studied.More-detailed investigations using advanced microscopic techniques revealed that biofilm morphology can be much more complex. Confocal scanning laser microscopy and computerized image analysis tools were used to show that glucosegrown P. aeruginosa biofilms were composed of cell clusters separated by interstitial voids and channels (6,7,26,39,46). Based on these observations, biofilms containing these clusters were referred to as having a cluster-and-channel morphology and the clusters were visualized as "mushrooms" (3). Also other aerobic, multispecies biofilms have been found to contain a structured cell cluster-and-channel arrangement (10).Anaerobic aggregates from anaerobic wastewater treatment plants are a special type of biofilms. These spherical biofilms are formed sp...

The feasibility of using the thermodilution method to monitor cardiac output during artificial ventilation was studied in anesthetized pigs. Normal saline (0.5 ml) at room temperature was injected into the left ventricle or the right atrium. The dilution curves were detected in the aortic arch and the pulmonary artery, respectively. The ventilation rate was 10 cycles/min at end-expiratory pressures of 0, 5, 10, and 15 cmH2O. For each level, 50 measurements of cardiac output were performed at regular intervals over the ventilatory cycle. The order of measurements were randomly selected. The average of each series of 50 measurements showed excellent correlation with the estimates of cardiac output based on the direct Fick method for oxygen. The maximum difference between the values of cardiac output randomly measured by the thermodilution method was 40% for the left side of the heart and 70% for the right side. However, when the values of cardiac output were sorted according to the specific phases of the respiratory cycle, there was a systematic variation with a small random error. For the left side of the heart, a satisfactory moment of injection for estimation of mean cardiac output appeared to be at the end of the spontaneous expiration. On the other hand, the analysis of cardiac output values at the right side did not reveal any satisfactory moment for injectate administration under changing circumstances, e.g., positive end-expiratory pressure.

The diffusing capacity, when normalized per liter of alveolar volume (DL,CO/VA) decreases in normal adults, whereas their total diffusing capacity (DL,CO) increases as alveolar volume (VA) increases. We studied these relationships in a group of normal children below 20 years of age. Diffusion variables were determined using the single breath technique. The effects of sex, age, and height on these relationships were estimated. DL,CO increased and DL,CO/VA decreased as alveolar volume increased. DL,CO and DL,CO/VA reference values at total lung capacity (TLC) appeared to be comparable to reference values at TLC in the literature. Reference values of DL,CO and DL,CO/VA derived from measurements at various alveolar volumes also predict similar values at TLC. The advantage of our reference equations is their applicability to patients with restrictive lung disease. Actual DL,CO/VA can be compared with reference DL,CO/VA at actual (restrictive) TLC instead of reference DL,CO/VA at reference TLC. This comparison extends the evaluation of a diffusion disorder. Pediatr Pulmonol. 1996; 21:84–89. © 1996 Wiley‐Liss, Inc.