Search PubMed⌕ Search

Biomedical subjects

W Mitzner

Publications and source records attributed to W Mitzner.

At least 109 records · Page 6Linked to original sources
PubMed1983

Pulmonary hemodynamics and gas exchange properties during progressive edema.

In this investigation we have studied the effect of increments of pulmonary edema on pulmonary hemodynamics, and physiological and hemodynamic shunt in an isolated lung preparation. Hemodynamic shunt was defined by the slope of the relationship between pulmonary arterial and airway pressures; when the slope decreases, there is a greater degree of shunt. Cardiovascular changes were analyzed using a Starling resistor model of the pulmonary circulation where the effective downstream pressure to flow as seen from the pulmonary artery exceeds the pulmonary venous outflow pressure. This effective downstream pressure is referred to as the critical pressure (Pc), and at low lung inflation the locus of this critical pressure is in extra-alveolar vessels. With 3-4 h of progressive edema to an average of 185% initial lobe weight we found a progressive rise in pulmonary arterial pressure (Ppa) from 12.1 to 21.5 cmH2O. About one-third of this increase in Ppa resulted from an increased Pc and the remainder resulted from an increased resistance upstream from the locus of Pc. These results are consistent with the hypothesis that the interstitial accumulation of fluid creates enough of an increase in interstitial pressure to compress extra-alveolar vessels. There was no significant correlation between the amount of edema and the measured physiologic shunt, but the hemodynamic shunt showed a highly significant correlation. The hemodynamic shunt theoretically measures the extent of obstructed airways and may be a useful index of the degree of pulmonary edema.

Animals↗
PubMed1983

Role of alveolar recruitment in lung inflation: influence on pressure-volume hysteresis.

The behavior of terminal lung units (alveoli) with changes in lung volume is controversial. For example, different investigators using similar techniques have suggested that alveoli expand homogeneously or, conversely, get smaller with increases in lung volume. We studied this problem by filling excised dog lobes with monodisperse aerosol and observing deposition at zero airflow. Under these conditions, the deposition of particles is inversely proportional to a mean alveolar linear dimension (ALD). With this technique, changes in ALD were assessed as the lung ventilated along its pressure-volume (PV) curve. PV curves were generated using a rapid cycling technique that minimized trapping and allowed reversible regulation of inflation-deflation hysteresis. Irreversible changes in PV hysteresis were assessed by rinsing the lung with Tween. With significant PV hysteresis, the ALD progressively decreased with inflation to total lung capacity (TLC). With deflation from TLC, the ALD was unchanged until low volumes were reached, when it decreased markedly. When PV hysteresis was minimized (reversibly or irreversibly), inflation and deflation ALD were superimposed. These data are consistent with progressive alveolar recruitment with inflation to TLC and derecruitment with deflation. The correlation between alveolar dimensions and PV hysteresis suggests that shifts in the PV curve can be accounted for by changes in the population of units. The number open at any given point is determined by the dynamic history of inflation.

Aerosols↗
PubMed1982

A new system for ventilating with high-frequency oscillation.

We describe simple high-frequency oscillation systems that incorporate a CO2 absorber and supply O2 on a need basis. These systems have the advantage of easy control of mean airway pressure and airway hydration and negligible loss of oscillatory tidal volume. Experiments done at constant tidal volume showed that as frequency (and hence total ventilation) increased, arterial CO2 tension (PaCO2) decreased. The fall in PaCO2 occurred until frequency reached approximately 20 Hz; above 20 Hz further increases in frequency had little or no effect on PaCO2. Because of their practical advantages the techniques described here may be quite useful in a clinical setting where an oscillator, rather than jet-type high-frequency, ventilation system is desired.

Animals↗
PubMed1982

Influence of betamethasone on the development of mechanical properties in the fetal rhesus monkey lung.

Previous investigations of the effect of glucocorticoids on fetal lung development have suggested that changes in lung structural properties may be of greater functional significance than changes in lung surfactant. In this study we examined the mechanism of the glucocorticoid-induced change in lung structure and compared it with the changes that occur during normal development. Rhesus monkeys (Macaca Mulatta) were treated with betamethasone prior to 133 days gestational age and then delivered by cesarian section either at 133 days or near term at 160 days. Our results show that normal fetal lung development over the last month of gestation occurs with a 45% increase in lung dry weight and a 56% increase in the maximal air volume per gram lung (Vmax/g). The immediate effect of the steroid was to cause a similar percentage increase in Vmax/g but no increase in lung weight. In fact, there were significant decreases in lung weight at both 133 and 160 days in the treated animals. In addition, we found no significant changes in the mean alveolar size either with normal development or with the steroid treatment. We thus conclude that in the rhesus monkey, the lung maturation process involves both an increase in lung mass and an increase in the number of alveoli per gram of that mass. The betamethasone treatment results in accelerated recruitment of alveoli coupled with impaired growth of lung tissue.

Animals↗
PubMed1981

Long-term effects of betamethasone on fetal development.

In previous studies, we noted that treatment of pregnant rhesus monkeys with betamethasone resulted in a marked increase in fetal lung distensibility. The purpose of the present study was to determine whether these changes persisted during subsequent in utero development. Pregnant rhesus monkeys were treated with 2 mg of betamethasone intramuscularly from day 120 to day 133 and underwent delivery by cesarean section one month later. The treated fetuses were found to have smaller lungs (-31%; p less than 0.005), and lower alveolar stability (-14%; p less than 0.025) than the control fetuses. Additional findings included smaller weights for the brain (p less than 0.01), liver, pancreas, and heart (p less than 0.05). Smaller adrenal (p less than 0.025) and larger pituitary weights (p less than 0.05) and lower plasma corticoid concentrations (p less than 0.001) indicated long-standing adrenal insufficiency in the treated fetuses. These persistent sequelae caution the indiscriminate and prolonged use of these potent glucocorticoids during pregnancy.

Adrenal Cortex↗
PubMed1981

The relationship of amniotic fluid fluorescence polarization to neonatal lung function.

Steady-state fluorescence polarization (FP) of 1,6-diphenyl-1,3,5-hexatriene (DPH) in monkey and human amniotic fluid was studied over a wide range of gestational ages. In both of these systems, the fluorescence polarization decreased with advancing gestational age. In the monkey, these measurements were correlated with both biochemical and physiologic parameters of lung function, including maximal lung volume, alveolar stability, percentage of disaturated phosphatidylcholine in lung homogenate, and lecithin/sphingomyelin ratio of amniotic fluid. Fluorescence polarization values correlated well with the lung disaturated phosphatidylcholine content expressed as a percentage of phosphatidylcholine, thus suggesting that the fluorescent probe interacts with a fraction of the amniotic fluid which is closely related to development of the pulmonary surfactant. system. Comparison of monkey and human amniotic fluid fluorescence polarizations showed a greater anisotropy of DPH in the monkey fluid at all stages of gestation, thereby indicating a greater microviscosity in monkey pulmonary surfactant.

Amniotic Fluid↗
PubMed1981

Amniotic fluid absorbance at 650 nm: a comparison with fetal lung maturity characteristics.

Using the rhesus monkey as an animal model we measured several indices of fetal lung maturation including pressure-volume characteristics and phospholipid concentrations and correlated them with the absorbance of amniotic fluid at 650 nm (A650). Those parameters, which are indicative of the presence of surfactant (i.e., deflation stability, lecithin-sphingomyelin ratio, lung phosphatidylcholine, as well as disaturated phosphatidylcholine), correlate significantly with the amniotic fluid A650, even after correction for gestational age. Maximal lung volume changes, thought to be reflective of alterations in tissue forces, did not correlate with A650. These data in the rhesus fetus indicate that the A650 reflects pulmonary surfactant characteristics independent of gestational age. Accordingly, this test may prove to be an accurate predictor of the risk of the respiratory distress syndrome.

Amniotic Fluid↗
PubMed1981

Glucocorticoids, hyperinsulinemia, and fetal lung maturation.

Glucocorticoids are reported to accelerate fetal lung development, whereas insulin is alleged to interfere with this effect of glucocorticoids. A paradox exists, however, in that glucocorticoids also induce hyperinsulinemia. The purpose of this study was to explore the interrelationships of betamethasone, hyperinsulinemia, and hyperglycemia to fetal lung maturation. In this rhesus preparation, maternal betamethasone administration produced an alarming increase in maternal and fetal plasma insulin values. A significant increase in total lung volumes also occurred, but lung surfactant properties (as measured by amniotic fluid lecithin/sphingomyelin concentrations, lung alveolar deflation stability, and lung phosphatidylcholine concentrations) remained unchanged. These findings are consistent with the following hypotheses: (1) Betamethasone-induced hyperinsulinemia impairs acceleration of surfactant production but does not negate increases in maximum lung volume; (2) betamethasone-induced increases in maximum lung volume occur through mechanisms other than alveolar surfactant alterations.

Amniotic Fluid↗
PubMed1981

Mechanical properties of contracted canine bronchial segments in vitro.

Airways of 2-5 mm in diameter were dissected from fresh dog lungs and mounted in a tissue bath so that they could be inflated and deflated with air. Length was held constant, and pressure and volume were monitored on an X-Y recorder. Pressure-volume curves were obtained for each airway at several difference degrees of constriction, by varying the concentration of acetylcholine (ACh) in the bath. Properties of the tissue were analyzed cy cycling airways at different speeds and by inflating them to various pressures. Circumferential length-tension curves were calculated from the inflation limbs of pressure-volume curves obtained by slow cycling (90 s for a complete cycle between -10 and 40 cmH2O). Administration of a series of increasing concentrations of ACh resulted in length-tension curves that were displaced to shorter lengths but not greatly altered in slope. These results suggest that slow inflation of the bronchus stretched only passive elements in series with a contractile element which shortened to the length determined by the concentration of ACh present.

Animals↗
PubMed1981

Hypoxic vasoconstriction and fluid filtration in pig lungs.

We have studied the effect of hypoxia [inspired partial pressure of O2 (Po2) 50 mmHg] on the relationships among pulmonary blood flow, pulmonary arterial pressure, and fluid filtration rates in isolated blood-perfused pig lungs. Our results indicate that hypoxia constricted the vasculature in a manner that caused a parallel shift of the pressure-flow curve to higher pressures. During normoxia, filtration rate was zero at flows less than 1.5 1/min but increased with increases in blood flow above this level. In both cases the shape of this relationship was similar, but during hypoxia it was shifted to higher filtration rates. These findings can be interpreted using a parallel-channel Starling resistor model of the lung with a distribution of critical pressures. All the effects of hypoxia found in this study could be explained simply by an increase in critical pressure. According to the model, this increase in critical pressure during hypoxia caused a greater filtration rate because of an increase in the mean intravascular filtration pressure and an increase in the mean filtration coefficient.

Animals↗
PubMed1981

Betamethasone and the rhesus fetus: effect on lung morphometry and connective tissue.

Pregnant rhesus monkeys (Macaca mulatta) at 67 to 85% of term pregnancy were treated with betamethasone for 3 days and then delivered by cesarean section. These treated fetuses had larger lung volumes (32.6 +/- 1.8 ml/kg of body weight) compared to gestational age-matched controls (22.9 +/- 3.2 ml/kg of body weight; P less than 0.025) but no alterations in surfactant properties as measured by amniotic fluid L/S ratios, alveolar deflation stability, or lung phosphatidylcholine. These findings suggest that betamethasone effects an increase in fetal lung volume by some method other than alteration in alveolar surfactant concentrations. Results also demonstrated an 11% increase in the collagen to elastin concentration in the treated fetuses as compared to the control animals (P less than 0.01), suggesting alterations in lung connective tissue. Morphometric studies done on the air-fixed inflated lung demonstrated a decrease in the number of alveoli per unit volume of lung among the treated animals (0.95 +/- 0.07 x 10(6)) compared to the control animals (1.19 +/- 0.08 x 10(6); P less than 0.025) and a reduction in the mean surface area of the lungs of the treated animals (506 +/- 10 cm2 per cm3) compared to the control animals (561 +/- 9 cm2 per cm3; P less than 0.005). These findings suggest that at least part of the increased maximal lung volumes is related to increased alveolar distensibility. Together, these pressure volume findings, biochemical studies, and morphometric analyses indicate that a major effect of betamethasone on the rhesus fetal lung is to alter lung connective tissue characteristics. Alterations in lung surfactant appear to be of less functional significance in this rhesus fetal model. The disparity between these findings and other animal studies might be due to differences in species, the preparation, or the method of glucocorticoid administration.

Animals↗
PubMed1980

Analysis of pulmonary vascular interdependence in excised dog lobes.

The pressure-volume behavior of intraparenchymal extra-alveolar arteries and veins was measured at various lung inflation states by inflating and deflating the vasculatures with air. The vascular volumes at specific vascular pressures (Pv) and transpulmonary pressures (Ptp) were partitioned into components of axial length and cross-sectional area. An analysis of the interrelationships between the perivascular pressure (Px), the vascular pressure vs. cross-sectional area behavior, and the Ptp is presented. For in vivo values of Pv, at functional residual capacity, the vascular-parenchymal mechanical interaction was small and values of arterial and venous Px approximately Ppl. With increasing Ptp to 30 cmH2O, values of both the arterial and venous Px relative to Ppl (Px - Ppl) decreased to approximately -5 cmH2O, indicating that the magnitude of the vascular-parenchymal interaction with increasing Ptp is similar for both arteries and veins in the in vivo state. At any fixed Ptp, values of arterial and venous Px - Ppl decreased nearly linearly with decreasing vascular cross-sectional area. These results were generally consistent with a linear continuum elasticity solution relating stress and deformation in the perivascular parenchyma.

Animals↗
PubMed1979

Betamethasone and the rhesus fetus: multisystemic effects.

In this controlled study of betamethasone administration to pregnant rhesus monkeys, using dosages per gram of fetal body weight similar to those reported in several human clinical studies, the most significant fetal pulmonary changes observed were increases in maximum lung volumes. The fact that comparable increases in peak volumes were demonstrated on saline filling supports our contention that these changes are related primarily to lung structural alterations rather than surfactant effects. Additional findings in the treated animals included reduced fetal head circumference, thymus weight, adrenal weight, placental weight, and maternal postoperative weight and increased fetal hepatic weight. Any of these glucocorticoid-induced changes could portend serious side effects. Further studies are needed to delineate the risk:benefit ratio of such treatment.

Adrenal Glands↗
PubMed1979

Effect of betamethasone on pressure-volume relationship of fetal rhesus monkey lung.

We have investigated the acceleration of fetal lung maturity following glucocorticoid administration. Air-filling of saline-filling pressure-volume curves were obtained on fetal rhesus monkey lungs after treatment with betamethasone. With air filling there was a marked increase in the total lung capacity (ml air/g at 40 cmH2O) in the treated animals. By normalizing the curves and plotting volume as a percent maximal volume, we examined the shape of deflation curves, a common functional measure of surfactant activity. We found little difference in the shapes between control and steroid-treated animals. With saline filling there was also a similar increase in the lung capacity. As surface tension has a negligible effect on saline pressure-volume curves, we conclude that the primary functional effect of glucocorticoids on the fetal lung may not be an alteration of surface forces. Rather the glucocorticoids seem to accelerate maturity more by increasing lung compliance through structural changes that allow the lung to contain more air for equivalent transpulmonary pressures or pressure changes. This may occur either by increasing the distensibility of already inflatable alveoli or by recruiting new units.

Animals↗
PubMed1979

Reverse nitrogen gradients in the study of phase III and cardiogenic oscillations of the single-breath nitrogen test.

The slope of phase III, phase IV, the slope of phase IV, and cardiac oscillations were measured on tracings obtained by both the regular single-breath N2 test (Tech I) and by a reverse technique (Tech II) in 9 healthy volunteers. Tech II consisted of 3 consecutive vital capacities (VC) of 100% O2 followed by one VC of room air. Theoretically, this should create a reversed apicobasal N2 gradient quantitatively similar to that of Tech I. From the total lung capacity following the VC2 of air, we monitored N2 concentration continuously at the mouth during a slow expiration in a manner similar to that of the single-breath N2 test. With Tech II, it is possible to preserve phase IV and its reversed slope in the presence of an almost flat slope of phase III and markedly blunted cardiac oscillations. When compared to Tech I, the slope of phase III with Tech II decreased from 0.66+/-0.20% N2/L (mean +/-SD) to 0.19+/-0.12 (p is less than 0.001), and cardiac oscillations decreased from a mean % N2 change with each heart beat of 0.87+/-0.37 to 0.24+/-0.21 (p is less than 0.005), whereas phase IV, although reversed in direction, remained quantitatively unchanged (0.35+/-0.15 L with Tech I and 0.37+/-0.14 L with Tech II), and the slope of phase IV tended to increase (2.7+/-1.9% N2 with Tech I and 3.4+/-2.1% N2 with Tech II, p=NS). We conclude that the N2 gradients within the lungs responsible for the slope of phase III and cardiac oscillations are largely independent of the gradients that give rise to phase IV and the slope of phase IV.

Adult↗