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Biomedical subjects

J Geiser

Publications and source records attributed to J Geiser.

At least 19 recordsLinked to original sources
PubMed2001

Training high--living low: changes of aerobic performance and muscle structure with training at simulated altitude.

This study was undertaken to test the hypothesis that endurance training in hypoxia is superior to training of the same intensity in normoxia. To avoid adaptation to hypoxia, the subjects lived under normoxic conditions when not training. A secondary objective of this study was to compare the effect of high- vs. moderate-intensity training on aerobic performance variables. Thirty-three men without prior endurance training underwent a cycle ergometer training of 6 weeks, 5 d/week, 30 minutes/d. The subjects were assigned to 4 groups, N-high, N-low, H-high and H-low based on the training criteria normoxia (N; corresponding to a training altitude of 600 m), vs. hypoxia (H; training altitude 3850 m) and intensity (high; corresponding to 80% and low: corresponding to 67% of VO2max). VO2max measured in normoxia increased between 8.5 to 11.1%, independent of training altitude or intensity. VO2max measured in hypoxia increased between 2.9 and 7.2%. Hypoxia training resulted in significantly larger increases than normoxia training. Maximal power that subjects could maintain over a thirty-minute period (measured in normoxia or hypoxia) increased from 12.3 - 26.8% independent of training altitude. However, subjects training at high intensity increased performance more than subjects training at a low intensity. Muscle volume of the knee-extensors as measured by magnetic resonance imaging increased significantly in the H-high group only (+ 5.0%). Mitochondrial volume density measured by EM-morphometry in biopsy samples of m. vastus lat. increased significantly in all groups with the highest increase seen in the H-high group (+ 59%). Capillary length density increased significantly in the H-high group only (+ 17.2%). The main finding of this study is that in previously untrained people, training in hypoxia while living at low altitude increases performance in normoxia to the same extent as training in normoxia, but leads to larger increases of aerobic performance variables when measured under hypoxic conditions. Training intensity had no effect on the gain of VO2max. On the level of skeletal muscle tissue, the combination of hypoxia with high training intensity constitutes the most effective stimulus for increasing muscle oxidative capacity.

Acclimatization↗
PubMed2001

Molecular adaptations in human skeletal muscle to endurance training under simulated hypoxic conditions.

This study was performed to explore changes in gene expression as a consequence of exercise training at two levels of intensity under normoxic and normobaric hypoxic conditions (corresponding to an altitude of 3,850 m). Four groups of human subjects trained five times a week for a total of 6 wk on a bicycle ergometer. Muscle biopsies were taken, and performance tests were carried out before and after the training period. Similar increases in maximal O(2) uptake (8.3-13.1%) and maximal power output (11.4-20.8%) were found in all groups. RT-PCR revealed elevated mRNA concentrations of the alpha-subunit of hypoxia-inducible factor 1 (HIF-1) after both high- (+82.4%) and low (+78.4%)-intensity training under hypoxic conditions. The mRNA of HIF-1alpha(736), a splice variant of HIF-1alpha newly detected in human skeletal muscle, was shown to be changed in a similar pattern as HIF-1alpha. Increased mRNA contents of myoglobin (+72.2%) and vascular endothelial growth factor (+52.4%) were evoked only after high-intensity training in hypoxia. Augmented mRNA levels of oxidative enzymes, phosphofructokinase, and heat shock protein 70 were found after high-intensity training under both hypoxic and normoxic conditions. Our findings suggest that HIF-1 is specifically involved in the regulation of muscle adaptations after hypoxia training. Fine-tuning of the training response is recognized at the molecular level, and with less sensitivity also at the structural level, but not at global functional responses like maximal O(2) uptake or maximal power output.

Acyl-CoA Dehydrogenase↗
PubMed1999

Expression of the mouse metallothionein-I and -II genes provides a reproductive advantage during maternal dietary zinc deficiency.

The function of metallothionein in zinc homeostasis was examined by using mice homozygous for knockout (KO) of the metallothionein-I or -II (MT-I and MT-II) genes. Pregnant MT-I/II KO mice or control mice were fed a zinc-deficient (1 microg/g or 5 microg/g) diet or a zinc-adequate (50 microg/g) diet during specific periods of pregnancy, and the effects on morphogenesis of the embryos were determined at day 14 of pregnancy (day 1 = vaginal plug). In the homozygous MT-I/II KO, as well as in the nontransgenic control mice, severe dietary zinc deficiency (1 microg/g) beginning on day 1 of pregnancy was embryotoxic and teratogenic, and the majority of the embryos in both strains were dead by mid-gestation. However, 53% of the surviving embryos in the MT-I/II KO mice were morphologically abnormal compared to only 32% of the embryos in the control mice. In subsequent experiments, moderate dietary zinc deficiency (5 microg/g beginning on day 1 of pregnancy or 1 microg/g dietary zinc beginning on day 8 of pregnancy) exerted teratogenic, but not embryotoxic effects. Embryos in the MT-I/II KO mice were 260 to 290% as likely to develop abnormally than were embryos in the control mice fed these same diets. These results demonstrate that the expression of the MT-I and -II genes in pregnant females improves reproductive success during maternal dietary zinc deficiency.

Animals↗
PubMed1995

Effect of RBC shape and deformability on pulmonary O2 diffusing capacity and resistance to flow in rabbit lungs.

Isolated rabbit lungs were perfused with washed and resuspended human red blood cells (RBCs) in the presence of drugs known to change the shape and deformability of RBCs. With sodium salicylate (0.5-2 g/l), which causes echinocytosis and increases RBC deformability, lung diffusing capacity for O2 (DLO2) increased by 21%. When chlorpromazine, which induces stomatocytosis and stiffens RBCs, was given (50 mg/l), DLO2 decreased by 18%. With sodium salicylate, the mean pulmonary artery pressure dropped by 14% from control values, whereas it increased by 18% under chlorpromazine. Comparative experiments with hemoglobin solutions did not reveal any effect of those two drugs either on DLO2 or on pulmonary arterial pressure, which indicates that the effects of sodium salicylate and chlorpromazine were due to changes in RBC shape and deformability. It is concluded that RBC shape and deformability affect pulmonary artery pressure and oxygen diffusing capacity, which may have an influence on oxygen transfer to tissue and hence be of clinical relevance.

Animals↗
PubMed1991

Lung diffusing capacity and red blood cell volume.

The aim of this study was to test whether a large surface to volume ratio of the red blood cells is advantageous for O2 transfer in lungs. Suspensions of washed large (human) and small (sheep) red blood cells were used to perfuse in random order isolated cat lungs (n = 7). The lungs were kept at 27 degrees C, ventilated with 1.0 l/min and perfused with 110 ml/min. Hemoglobin concentration was 70 g/l. Assuming an inhomogeneous lung with an alveolar dead space compartment, pulmonary diffusing capacity for O2 (DLO2) was 0.53 +/- 0.10 ml.min-1.mmHg-1 (mean +/- SD) when perfusing with sheep red cells and 0.52 +/- 0.13 with human red cells. On the basis of a lung model with a low VA/Q and a high VA/Q compartment the values were 0.86 and 0.93. Thus, DLO2 was not larger with smaller red blood cells, i.e. with higher red cell surface area per blood volume. Possible explanations for this unexpected result are discussed.

Animals↗
PubMed1989

Gas transfer in isolated lungs perfused with red cell suspension or hemoglobin solution.

Rapid mixing experiments have shown that the reaction between oxygen and hemoglobin is faster in hemoglobin solutions than in red cell suspensions. In this study we tested whether this observation can also be made in the lung. Excised rabbit lungs were perfused either with washed human red cell suspensions or with hemoglobin solutions, each with 50 g hemoglobin/L, and steady-state diffusing capacities (DLO2) for oxygen elimination measured. Mean settings were a temperature of 29.5 degrees C of the inflowing and outflowing perfusate of the lung, a total ventilation of 1.7 L.min-1, and a perfusion rate of 116 ml.min-1. Under those conditions resulted a DLO2 with hemoglobin solution of 0.68 +/- 0.18 ml.min-1.mm Hg-1, and a significantly lower value of 0.50 +/- 0.06 ml.min-1.mm Hg-1 with red cell suspension (P less than 0.01). An extraerythrocytic diffusing resistance, formed by a plasma layer and/or arising from a dynamic diffusion boundary layer, which is also known as unstirred layer, could explain the lower value with red cell suspensions.

Animals↗
PubMed1989

Resistance of mammalian red blood cells of different size to hypertonic milieu.

1. The resistance of different mammalian red blood cells (RBCs) to hyperosmotic environments was studied. RBCs of six mammalian species were exposed to 10 increasingly hyperosmotic NaCl solutions for 24 hr at 5 degrees C. 2. The osmolality at which the amount of liberated haemoglobin reached a preset level (e.g. 3-4% of the total haemoglobin) showed a linear correlation with negative slope with RBC volume. This indicates that small RBCs are more resistant to hyperosmotic milieu than large ones. 3. A similar relation can be found from literature data when maximal urinary tonicities are plotted as a function of RBC volume, i.e. animals with the ability to produce highly concentrated urine have small RBCs. 4. RBC volume and maximal urinary tonicity in mammals are therefore tightly linked. Future research will have to show whether this correlation is fortuitous or not and whether, as can be speculated, RBC size is directly or indirectly regulated by the kidney.

Adult↗
PubMed1986

Effects of altering dead space volume on respiration and air sac gases in geese.

Dead space volume (VD) was altered in spontaneously breathing, anesthetized geese from values far above (about 115 ml) to those far below (about 3 ml) the normal VD (approximately 40 ml). Respiratory gases were measured in cranial (CrS) and caudal air sacs (CdS) and in blood. The major findings were as follows: Ventilation increased linearly with VD, by increases in tidal volume (VT) at constant breathing rate (fresp); effective parabronchial ventilation, (VT-VD) X fresp, remained constant and so did arterial blood gases. No changes occurred in CrS gas composition. CdS PCO2 declined with decreasing VD, and the respiratory exchange ratio increased, reaching values above unity at the lowest VD. The gas composition in CrS, and particularly its relation to end-expired gas composition, is in agreement with current models of the gas flow pattern in the avian lung. The PCO2 values in CdS are higher than expected by simple models, e.g. by dead space re-inhalation. Neopulmonic gas exchange and incomplete gas mixing are suggested to contribute significantly to the gas composition of CdS.

Air Sacs↗
PubMed1984

Effects of increasing metabolism by 2,4-dinitrophenol on respiration and pulmonary gas exchange in the duck.

The effects of pharmacologically elevated metabolism on respiration and parabronchial gas exchange were studied in the anesthetized, spontaneously breathing duck using 2,4-dinitrophenol (DNP), injected in successive single doses of 1.2-2.5 mg per kg body mass. Oxygen uptake, MO2, increased with the cumulative amount of DNP, reaching a sevenfold resting level at the highest DNP level tolerated, 15 mg/kg. Ventilation increased nearly as much as MO2, mainly by an increase in respiratory frequency, fresp. Cardiac output increased somewhat less than MO2, mediated by increases in both cardiac frequency and stroke volume. Arterial blood-gases showed little change; however, mixed venous PO2 dropped significantly, and PCO2 increased significantly, with stimulated metabolism. Pulmonary diffusing capacity, DO2, showed a significant rise with MO2, beyond that expected from a reduction of functional lung heterogeneity. The results show that pharmacological stimulation of metabolism can evoke responses in the respiratory and circulatory systems that are comparable to those observed with exercise. The mechanism by which parabronchial diffusing capacity increases during elevated metabolism remains to be investigated.

2,4-Dinitrophenol↗
PubMed1983

Simultaneous O2 and CO diffusing capacity estimates from assumed lognormal VA, Q and DL distributions.

O2 and CO pulmonary transfer data obtained in dogs under steady-state conditions in hypoxia by Savoy et al. (Respir. Physiol. 42: 43-59, 1980) have been submitted to reevaluation and have yielded new estimates of the lung diffusing capacity, DL. For the proposed DL computation it has been assumed that functional inhomogeneity can be considered as resulting from lognormal distributions of the VA/Q and VA/DL ratios. The standard deviation, sigma, of the VA/Q distribution is computed from the measured (PA -Pa)CO2, and the same sigma value is assumed to prevail for the VA/DL distributions. This is equivalent to assume constant DL/Q ratios in the entire lung. With the so defined distributions, DL values, called D sigma O2 and D sigma CO, were sought, for which the model calculations yielded O2 partial pressures and CO fluxes equal to those measured. Compared with DL estimates computed with conventional procedures, these results show that D sigma O2 is twice as large as DLO2 computed with ideal alveolar PO2 and that D sigma CO lies between DLCO computed with the mean alveolar PCO and that computed with the ideal alveolar PCO. The D sigma O2/D sigma CO ratio was on the average 1.2, a value which, unlike the ratios obtained with conventional DLO2 and DLCO estimates, is in good agreement with the characteristics of diffusion and of chemical association of O2 and CO with blood.

Animals↗
PubMed1981

Gas tension profile of the lung of the viper, Vipera xanthina palestinae.

Oxygen and carbon dioxide concentrations along the lung of five awake, resting Palestine vipers were continuously measured by mass spectrometry. Ventilatory volumes, body wall movements and heart rate were also measured. In the anterior part of the faveolar (respiratory) lung, oxygen and carbon dioxide concentrations returned to within 1% of inspired composition with each inspiration. Between breaths, changes of 0.5-2% in gas concentrations were seen in the faveolar region but practically no changes occurred in the caudal, non-respiratory lung (air sac) where mean oxygen and carbon dioxide concentrations of 16.4% and 2.5% respectively were recorded. The respiratory exchange ratio dropped from near 1.5 in the anterior faveolar region to zero in the transition zone to the air sac. Instantaneous R values declined with breath-holding time in each location along the length of the lung. Gas exchange appears greatest in the posterior faveolar region near the heart and there is evidence of cardiogenic gas mixing in this region. The posterior air sac may either passively respond to air movements in the anterior lung or it may participate in ventilation. During periods of extended breath-holding (10-15 min) pronounced body wall movements were seen but there was no air flow from the mouth and gas exchange continued in the lung with rapidly decreasing R.

Animals↗
PubMed1981

Airflow in the avian respiratory tract: variations of O2 and CO2 concentrations in the bronchi of the duck.

Variations of CO2 and O2 concentrations within a respiratory cycle were recorded at various sites in the bronchial system of anesthetized, spontaneously ventilating ducks, using small metal cannulae introduced into the main bronchus (MB), a medioventral (MV) or mediodorsal (MD) secondary bronchus and connected to a mass spectrometer for continuous gas analysis. The following results were obtained and conclusions drawn. (1) Since during inspiration, CO2 concentration (FCO2) was close to zero all along MB and since FCO2 was nearly constant throughout the respiratory cycle in MV, it must be inferred that on inspiration, no significant amount of air passes directly either from MV to MB or in the opposite direction, there being thus a complete functional valving of the MV orifices. In particular the Hazelhoff loop mechanism (inspiratory reflux of lung gas into the MB) is not operative. (2) During expiration, FCO2 in MV was only slightly higher than that in the trachea, but substantially above FCO2 deep in MB. This suggests that most of the expiratory flow from caudal air sacs is diverted through the paleopulmo and only little exits directly through MB. It is shown that the functional valving of bronchial air flow is advantageous for gas exchange as it reduces air shunts and provides a nearly steady lung ventilation.

Animals↗
PubMed1980

Comparison of steady state pulmonary diffusing capacity estimates for O2 and CO in dogs.

In view of the fact that the inhomogeneity effects on pulmonary diffusing capacity (DL) estimates are quite different for O2 and for CO, simultaneous determinations of steady-state DLCO and DLO2 were attempted and compared. To this end, pulmonary gas exchange was measured in 17 anesthetized and artificially ventilated dogs, in hypoxia with and without carbon monoxide in inspired gas (FIO2 = 0.12, FICO = 0.0009 to 0.0016). The diffusing capacity estimates were computed by two conventional procedures, the first (Dapp) taking into account the mean alveolar partial pressures and the second (DVDA) the ideal alveolar partial pressures. It was found that the presence of COHb in blood, inevitable in the steady-state DLCO procedure, leads to a marked underestimation of DLO2; therefore DLCO values could only be adequately compared to DLO2 values obtained in the absence of CO from inspired gas. These DLO2 were 18.5 and 33.4 mumol . min-1 . Torr-1 . kg-1 for the mean DappO2 and DVDAO2, respectively, whereas the DLCO values obtained after 15 to 25 min CO inspiration were 30.0 and 83.4 mumol . min-1 . Torr-1 . kg-1 for the mean DappCO and the mean DVDACO, respectively. The salient feature is that with both procedures the mean value of DLCO estimate is higher than the corresponding DLO2 estimate. This finding suggests that in anesthetized, artificially ventilated dogs DappO2 and DVDACO estimates obtained by steady-state procedures in hypoxia are largely influenced by inhomogeneity effects and of limited value for assessment of the diffusing properties of the lung. DappCO and DVDAO2 are also affected by inhomogeneities but to a lesser degree.

Animals↗
PubMed1980

Incomplete gas mixing in air sacs of the duck.

During normal breathing, the CO2 concentration in caudal air sacs of birds is higher, and the O2 concentration lower, than expected on the basis of the known air flow pattern. We have experimentally tested two hypotheses which could explain this finding: (1) Preferential shunting of re-inspired dead space gas into caudal air sacs; (2) Incomplete mixing of inspired and residential air sac gas. - Different portions of the inspired air in anesthetized ducks were labeled by injecting a small bolus of argon (Ar) into the trachea. The resulting Ar concentration was recorded continuously in the caudal thoracic air sac at the ostium and in deeper regions.-The amount of Ar entering the sac was found to be independent of the volume inspired prior to injection of the label, and hypothesis (1) thus dismissed. However, during inspiration and subsequent expiration the Ar bolus was found to be neither perfectly mixed within the inspired gas nor with the air sac residential gas. More than 10 sec of breath-hold were necessary for air sac gas to approach an equilibrium value. Gas layering (stratification) in caudal air sacs gas is proposed to cause the high CO2 and low O2 levels during steady state breathing, as air sac residential gas equilibrates with a layer of dead space gas that enters the air sac on each breath and contains a higher CO2 and lower O2 concentration than the mixed inspirate.

Animals↗
PubMed1979

Pulmonary O2 diffusing capacity estimates from assumed log-normal VA/Q distributions.

Steady-state pulmonary gas exchange has been measured in hypoxia in 33 mongrel dogs with the aim of comparing DLO2 estimates obtained with three procedures differing by the models assumed for functional inhomogeneity. In the first procedure the lung was assumed to be homogeneous and the corresponding DLO2 estimate was 15 mumol . min-1. Torr-1 . kg-1. In the second procedure, which is the one commonly used in respiratory physiology, alveolar dead space was considered as the unique form of functional inhomogeneity and the corresponding DLO2 estimate was 31 mumol . min-1. Torr-1 . kg-1. In the third procedure, which has been specially worked out for this study, functional inhomogeneity was represented by a log-normal distribution of the VA/Q ratios and the corresponding DLO2 estimate was 50 mumol . min-1 . Torr-1 . kg-1. The relation between the DLO2 estimates by the second and by the third procedures was found to depend upon the blood pH. This could be explained on the basis of the effects of acidosis on the blood capacitances for O2 and for CO2. Analysis suggests that in hypoxia where normally the O2 capacitance is about half the CO2 one, the third procedure yields DLO2 estimates about twice as large as those obtained by the second one.

Animals↗
PubMed1978

[Unrecognized hyperthyroidism in hospital patients. Analysis of clinical symptoms compared to aged euthyroid goiter patients].

During a 14-month period hyperthyroidism has been diagnosed in 39 of 2916 inpatients of a general medical service. Graves' disease was present in only 8 cases. 21 patients had solitary autonomous nodules or multiple autonomous nodules (toxic multinodular goiter). In 10 patients the type of hyperthyroidism could not be established. The referring practitioner suspected hyperthyroidism in all 8 patients with Graves' disease, but in only 5 of the 31 remaining cases. The relative rarity of Graves' disease in inpatients reflects the fact that this form of hyperthyroidism is easily recognized by the practitioner and treated on an out-patient basis. Graves' disease patients and those with autonomous solitary or multiple nodules were of comparable age and had an identical serum free-thyroxin. Thus, neither higher age nor lower thyroxin is responsible for the atypical clinical presentation of autonomous nodules. A comparison with age- and sex-matched carriers of euthyroid goiters identified weight loss, resting pulse rate over 90 and auricular fibrillation as reliable clinical features. A thyroid function test is therefore indicated in every patient with a goiter and one of the three above clinical findings.

Adenoma↗