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Biomedical subjects

H Heller

Publications and source records attributed to H Heller.

At least 37 records · Page 2Linked to original sources
PubMed1998

Nitric oxide used to test pulmonary gas exchange in rabbits.

To evaluate whether nitric oxide (NO) is an appropriate test gas for assessing pulmonary gas exchange, we determined the rates of disappearance from the alveolar space (lambda) of NO and singly and doubly 18O-labelled carbon dioxide (C16O18O, C18O2) by performing single-breath manoeuvres on seven artificially ventilated rabbits. By exploiting unique features of both isotopic species and by analysing pulmonary gas transport and lambda values with a commonly used model, we found that diffusion forms 98+/-6% (mean +/- SD) of the overall resistance to alveolar-capillary NO transfer. This means that measurements of pulmonary NO uptake reveal the entire diffusive properties of the alveolar-capillary membrane, because the extremely fast binding of NO to haemoglobin negates the "reactive" component within red blood cells of pulmonary capillaries.

Animals↗
PubMed1998

Stratification does not limit O2 uptake in rabbit lungs.

This study was performed to assess the role of stratification, i.e. axial gas mixing deficit within alveolar space, in limiting alveolar gas exchange for oxygen. The single-breath method for varying breath-holding time with oxygen-labelled carbon dioxide, C18O2, was applied to 10 anaesthetized, paralysed and artificially ventilated rabbits. Alveolar partial pressure of C18O2 was analysed using respiratory mass spectrometry. Starting from residual volume, the lungs were rapidly inflated using 40 mL of indicator gas mixture (1% C18O2 in nitrogen). After executing breath-holding, the lungs were rapidly deflated. Pulmonary diffusing capacity of carbon monoxide was determined in the same way. On the basis of a serial compartment model, the lower limit of the stratificational conductance of oxygen was estimated, using the rate constant of C18O2 removal from alveolar space (4 s-1) and Graham's law. We found that the stratificational conductance in rabbits amounts to at least 13.5 mL mmHg-1 min-1. The pulmonary diffusing capacity of oxygen was calculated by multiplying the carbon monoxide diffusing capacity of rabbit lungs by a factor of 1.2, yielding a value of 0.77 mL mmHg-1 min-1. These results show that stratificational conductance is at least 17.5 times higher than pulmonary oxygen diffusing capacity, indicating that stratification does not limit oxygen uptake in rabbit lungs.

Animals↗
PubMed1998

Respiratory physiology teaching: determination of residual volume by applying the indicator-dilution technique.

Apart from the current teaching of spirometric methods in laboratory courses on respiratory physiology, we have included an experiment in which medical students determine their own residual volume by applying the indicator-dilution technique. For hygienic reasons we used a bag-in-the-box system to dilute helium within alveolar space by performing the single-breath method. Although each participant independently underwent only one single-breath maneuver, we gained a reliable relationship between residual volume and subjects' height and body weight in 68 female (r = 0.6, P < 0.0001) and 99 male (r = 0.42, P < 0.0001) students. From this successful outcome and with the opportunity to discuss the limitations of the single-breath method as well, we inferred that this experiment affords a transparent and instructive approach to interpreting the determination of lung volumes on the basis of the indicator-dilution technique.

Adult↗
PubMed1998

Theta values for C16O18O and C18O2 related to respective pulmonary diffusing capacities.

The single-breath diffusing capacities for singly and doubly 18O-labeled CO2, DLC16O18O and DLC18O2, as well as for NO, were determined in seven anesthetized rabbits to investigate whether the theoretically predicted ratio of specific blood uptake rates of both isotopic CO2 species, theta C18O2/theta C16O18O = 2.0, can be derived from the measured values of DLC16O18O and DLC18O2. Data of DL were obtained by inflating the lungs with gas mixtures containing 0.35% C16O18O or 0.8% C18O2 or 0.05% NO in nitrogen, with breath-holding periods of 0.05-0.5 s and 2-12 s for the CO2 and NO tests, respectively. theta C18O2/theta C16O18O was calculated by applying the double-reciprocal Roughton-Forster equation to DL values obtained in each animal and by assuming that NO diffusing capacity represents the gas conductance of the alveolar-capillary membrane. The measured ratio was theta C18O2/theta C16O18O = 1.9 +/- 0.2 (mean +/- SD), thus comparing reasonably with the predicted one. Therefore, our findings provide evidence that the greater value of DLC18O2 is mainly due to the twofold higher probability (or theta value) for C18O2 than for C16O18O to disappear within red blood cells via isotopic exchange reactions.

Animals↗
PubMed1998

Single-breath CO diffusing capacity influenced by initial alveolar partial pressure of CO.

The purpose of this study was to assess the influence of incorrect determinations of the initial alveolar partial pressure of carbon monoxide (CO) at the beginning of breath holding (PIACO) on the pulmonary CO diffusing capacity of the lung (DLCO). Single-breath maneuvers were performed on 14 anesthetized and artificially ventilated rabbits, using 0.2% CO in nitrogen as the indicator gas mixture. Inflation and deflation procedures were carried out in an identical manner on each animal, with inflation always starting from residual volume. End-tidal partial pressure of CO was determined by respiratory mass spectrometry and was used to calculate DLCO values with the application of the three-equation (method 1), as well as the conventional (method 2), solution. In each rabbit, method 2 caused DLCO values to be overestimated when compared with method 1, and this overestimation decreased with increasing time intervals of CO uptake. Because we were able to recalculate this deviation using PIACO values that were obtained by taking the diffusive removal of CO during inflation into account, we concluded that errors in estimating PIACO by applying method 2 significantly contribute to the discrepancy between both methods.

Animals↗
PubMed1998

Pulmonary diffusing capacities for oxygen-labeled CO2 and nitric oxide in rabbits.

We determined the pulmonary diffusing capacity (DL) for 18O-labeled CO2 (C18O2) and nitric oxide (NO) to estimate the membrane component of the respective gas conductances. Six anesthetized paralyzed rabbits were ventilated by a computerized ventilatory servo system. Single-breath maneuvers were automatically performed by inflating the lungs with gas mixtures containing 0.9% C18O2 or 0.05% NO in nitrogen, with breath-holding periods ranging from 0 to 1 s for C18O2 and from 2 to 8 s for NO. The alveolar partial pressures of C18O2 and NO were determined by using respiratory mass spectrometry. DL was calculated from gas exchange during inflation, breath hold, and deflation. We obtained values of 14.0 +/- 1.1 and 2.2 +/- 0.1 (mean value +/- SD) ml.mmHg-1.min-1 for DL(C18O2) and Dl(NO), respectively. The measured DL(C18O2)/DL(NO) ratio was one-half that of the theoretically predicted value according to Graham's law (6.3 +/- 0.5 vs. 12, respectively). Analyses of the several mechanisms influencing the determination of DL(C18)2 and DL(NO) and their ratio are discussed. An underestimation of the membrane diffusing component for CO2 is considered the likely reason for the low DL(C18O2)/DL(NO) ratio obtained.

Animals↗
PubMed1998

Role of reaction resistance in limiting carbon monoxide uptake in rabbit lungs.

The contribution of reaction resistance to overall resistance to pulmonary carbon monoxide (CO) uptake [DLCO/(ThetaCO . Vc), where DLCO is lung CO diffusing capacity, ThetaCO is CO uptake conductance of erythrocytes, and Vc is pulmonary capillary blood volume] was determined in 10 anesthetized, paralyzed, and artificially ventilated rabbits. On the basis of the classical double-reciprocal equation of F. G. W. Roughton and R. E. Forster (J. Appl. Physiol. 11: 290-302, 1957), DLCO/(ThetaCO . Vc) was obtained by solving the relation DLCO/(ThetaCO . Vc) = 1 - 2/(DLNO/DLCO), where DLNO/DLCO represents the ratio between the respective single-breath diffusing capacities (DL) of nitric oxide (NO) and CO pulmonary capillary blood. The lungs of eight rabbits were inflated, starting from residual volume, by using 55 ml of indicator gas mixture (0.2% CO and 0.05% NO in nitrogen). DL values were calculated by taking the end-tidal partial pressures of CO and NO as analyzed by using a respiratory mass spectrometer. The overall value was DLCO/(ThetaCO . Vc) = 0.4 +/- 0.025 (mean +/- SD). Because of the use of O2-free indicator gas mixtures, the end-tidal O2 partial pressures were approximately 21 Torr. In one other rabbit, the application of 0.2% CO and 0.001% NO yielded DLCO/(ThetaCO . Vc) = 0.39; in the tenth rabbit, however, inspiratory volume was varied, and an identical value was found at functional residual capacity. We conclude that the contribution of reaction resistance to overall resistance to pulmonary CO uptake is independent of the inspiratory NO concentration used, including, with respect to the pertinent literature, the conclusion that in rabbits, dogs, and humans this contribution amounts to 40% when determined at functional residual capacity.

Animals↗
PubMed1997

Integration of foreign DNA and its consequences in mammalian systems.

The insertion of foreign DNA into the genomes of established cells and organisms and the consequences of this integration event are of significance for viral oncology, reverse genetics, transgenic organisms, human somatic gene therapy and evolution. This review summarizes recent experimental findings and focuses on the alteration of cellular DNA methylation at regions remote from the site of insertion. We also discuss experimental data demonstrating that foreign DNA ingested by mice is not completely degraded in their gastrointestinal tracts; fragments of this DNA have been found to be covalently linked to DNA with 70% homology to the mouse IgE receptor gene.

Animals↗
PubMed1997

Effect of inhaled nitric oxide on endotoxin-induced hypoxaemia in rabbits.

In five mechanically ventilated rabbits, we studied the property of inhaled nitric oxide in helping to treat hypoxaemia which was induced by intravenous endotoxin (Escherichia coli-derived lipopolysaccharide, serotype 0111: B4). We used measurements of arterial partial pressure of oxygen to check a therapeutic nitric oxide benefit. Pulmonary artery pressure was continuously monitored. Furthermore, we determined the single-breath diffusing capacity for nitric oxide. Measurements of plasma nitrite/nitrate concentration served as an indicator of endogenous nitric oxide output. The first infusion of endotoxin led to a transient pulmonary vasoconstriction, whereas arterial partial pressure of oxygen was permanently reduced by 30 +/- 10 mmHg (mean +/- SD), attaining minimal values of 48 +/- 3.4 mmHg due to additional endotoxin. Single-breath diffusing capacity for nitric oxide declined by 20 +/- 5.5% of baseline values until the experiments were concluded. Endotoxin induced an increase in plasma nitrite/nitrate concentration in the five rabbits as well as in the control animals (four rabbits) without exogenous nitric oxide supply. During the 25 inhalations of nitric oxide (3-50 ppm), arterial oxygenation did not change significantly. Thus endotoxin permanently impaired pulmonary gas exchange without inducing pulmonary hypertension. Inhaled nitric oxide did not improve arterial oxygenation during endotoxaemia.

Administration, Inhalation↗
PubMed1997

Convection as one of the limiting factors of human respiration during normoxic exercise.

Each of the pathways within respiration has been suspected of limiting maximal performance, suggesting that O2 transport may be affected by each single pathway. The use of the stable, isotopic O2 molecules 16O2 and 16O18O is presented as a novel method for assessing respiration. Because of their different molecular weights, 16O2 diffuses 3% more rapidly than 16O18O, whereas 16O2 is convectively transported as rapidly as 16O18O. This can be quantified by using the overall fractionation factor alpha O. The more diffusion becomes limiting, the more 16O2 is transported in preference to 16O18O and alpha O is increased to 1.03. By contrast, the more respiration is limited by convection, the closer alpha O comes to 1.0 during the entire O2 transport. Six untrained subjects underwent normoxic exercise on a cycle ergometer. Isotopic analysis was performed at rest and during exercise loads of 50, 100, 150, 200, and 250 W using respiratory mass spectrometry. With increasing workload, a decrease in alpha O from 1.0072 at rest to 1.0033 at 250 W was determined in all subjects. On the basis of a serial resistance model of respiration, we concluded that, in our subjects, O2 transport was increasingly affected by convection but decreasingly limited by diffusion. The relative contribution of convection to the entire resistance to O2 flow ranged from > or = 44.6% at rest to > or = 74.6% at the most strenuous level of exercise, whereas the diffusive pathways decreasingly contributed to resistance to O2 flow by < or = 24% at rest and < or = 11% at 250 W.

Adolescent↗
PubMed1997

Single-breath diffusing capacity of NO independent of inspiratory NO concentration in rabbits.

Pulmonary diffusing capacity of NO (DLNO) was determined by performing single-breath experiments on six anesthetized paralyzed supine rabbits, applying inspiratory concentrations of NO (FINO) within a range of 10 parts per million (ppm) < or = FINO < or = 800 ppm. Starting from residual volume, the rabbit lungs were inflated by 50 ml of a NO-nitrogen-containing indicator gas mixture. Breath-holding time was set at 0.1, 1, 3, 5, and 7 s. Alveolar partial pressure of NO was determined by analyzing the end-tidal portion from expirates, with the use of respiratory mass spectrometry. In the six animals, pulmonary diffusing capacity of NO averaged DLNO = 1.92 +/- 0.21 ml.mmHg-1.min-1 (mean +/- SD value). Despite extreme variations in FINO, we found very similar DLNO values, and in three rabbits we found identical values even at such different FINO levels of 80 ppm or 500, 20, or 200 ppm as well as 10 or 800 ppm. There was also no dependence of DLNO on the respective duration of the single-breath maneuvers. In addition, the time course of NO removal from alveolar space was independent of applied FINO levels. These results suggest that DLNO determinations are neither affected by chemical reactions of NO in alveolar gas phase as well as in lung tissue nor biased by endogenous release of NO from pulmonary tissue. It is our conclusion that the single-breath diffusing capacity of NO is able to provide a measure of alveolar-capillary gas conductance that is not influenced by the biochemical reactions of NO.

Administration, Inhalation↗
PubMed1997

Spiral computerized tomography in the evaluation of acute flank pain: a replacement for excretory urography.

PURPOSE: We determined the value of noncontrast enhanced spiral computerized tomography (CT) in the evaluation of suspected renal colic. MATERIALS AND METHODS: Thin section (5 mm.) noncontrast enhanced CT was used to evaluate 100 patients presenting to the emergency room with flank pain. The 55 patients with ureteral obstruction were followed at the urology outpatient clinic and by telephone interview, while 45 without ureteral obstruction were followed by telephone interview and chart review. Sensitivity, specificity, and positive and negative predictive values for CT were determined, with passage, retrieval or identification of a stone on a retrograde study considered the gold standard for diagnosis. RESULTS: A total of 89 patients had adequate clinical followup to assess outcome accurately. Of 55 patients with ureteral obstruction on CT 11 underwent endoscopic stone removal, while 44 were treated conservatively with stone passage documented in 39. Of the 45 patients without ureteral stones identified 38 did not pass calculi and CT provided a definite diagnosis in 14. There was 1 false-negative study. The results yielded 98% sensitivity, 100% specificity, and 100% positive and 97% negative predictive values. CONCLUSIONS: Noncontrast enhanced spiral CT was accurate and reliable in detecting obstructing ureteral calculi in patients with flank pain.

Acute Disease↗
PubMed1996

Chromosomal distribution of the hamster intracisternal A-particle (IAP) retrotransposons.

The retrotransposon-like elements of the intracisternal A-particle (IAP) sequences occur in about 900 copies per haploid hamster cell genome. By applying the fluorescent in situ hybridization (FISH) technique and four different, cloned segments of the IAP element as hybridization probes, these elements were found to be distributed in specific patterns over many of the 44 hamster chromosomes. The hybridization patterns were very similar regardless of whether all four probes or only the IAPI probe carrying the long terminal repeat (LTR) region were used. The IAP elements were found most abundantly, though not exclusively, on the short arms of at least 12 of the autosomes. Of the sex chromosomes, the shorter Y chromosome was stained on both arms, and the X chromosome on one arm by the IAP probes. Primary Syrian hamster cells, the established Syrian hamster cell line BHK21, and the adenovirus type 12 (Ad12)-transformed BHK21 cell line T637 yielded very similar results. In Chinese hamster ovary (CHO) or 3T3 mouse cells, signals could not be elicited by FISH using the Syrian hamster IAP probes. On Southern blots, the DNAs from these cell lines hybridized very weakly, if at all, to the IAP sequences. Thus, IAP sequences were retroposed after Syrian hamster and mouse or Syrian and Chinese hamsters had diverged in evolution.

3T3 Cells↗