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Biomedical subjects

W Mitzner

Publications and source records attributed to W Mitzner.

At least 73 records · Page 4Linked to original sources
PubMed1984

Lung compliance changes on high-frequency ventilation in normal dogs.

To test the hypothesis that high-frequency ventilation (HFV) promotes lung stability we compared the temporal course of dynamic lung compliance changes after two inflations on HFV with those occurring on conventional mechanical ventilation (CMV) at two different lung volumes, specifically with and without 5 cmH2O positive end-expiratory pressure (PEEP). In our first set of experiments we ventilated six anesthetized paralyzed dogs first with CMV, then with HFV, then again with CMV using tidal volumes of 15 ml/kg at rates of 16-18 times/min for CMV and less than 90 ml and a rate of 15 Hz for HFV. In our second set of experiments we ventilated six dogs for 4 h, the 1st h with CMV at 0 cmH2O end-expiratory pressure, the 2nd h with CMV with 5 cmH2O PEEP, the 3rd h with HFV at the same mean pleural pressure, and the 4th h again with CMV with 5 cmH2O PEEP. We found the decreases in dynamic compliance with time following hyperinflations were similar on HFV and CMV (P greater than 0.5) at both lung volumes. With the lower lung volume the initial dynamic compliance following hyperinflation also tended to fall progressively from one hour to the next despite the inflations. However, with PEEP the initial dynamic compliance over successive hours tended to rise from one hour to the next. We found that changes in dynamic compliance were not necessarily reflected in the venous admixture or alveolar to arterial O2 partial pressure gradients. We thus conclude that lung stability in normal dogs is not improved during HFV, and blood gases cannot be used to predict compliance changes.

Animals↗
PubMed1984

Physiological dead space during high-frequency ventilation in dogs.

Tidal volumes used in high-frequency ventilation (HFV) may be smaller than anatomic dead space, but since gas exchange does take place, physiological dead space (VD) must be smaller than tidal volume (VT). We quantified changes in VD in three dogs at constant alveolar ventilation using the Bohr equation as VT was varied from 3 to 15 ml/kg and frequency (f) from 0.2 to 8 Hz, ranges that include normal as well as HFV. We found that VD was relatively constant at tidal volumes associated with normal ventilation (7-15 ml/kg) but fell sharply as VT was reduced further to tidal volumes associated with HFV (less than 7 ml/kg). The frequency required to maintain constant alveolar ventilation increased slowly as tidal volume was decreased from 15 to 7 ml/kg but rose sharply with attendant rapid increases in minute ventilation as tidal volumes were decreased to less than 7 ml/kg. At tidal volumes less than 7 ml/kg, the data deviated substantially from the conventional alveolar ventilation equation [f(VT - VD) = constant] but fit well a model derived previously for HFV. This model predicts that gas exchange with volumes smaller than dead space should vary approximately as the product of f and VT2.

Animals↗
PubMed1984

Mean airway pressure and alveolar pressure during high-frequency ventilation.

Studies and applications of high-frequency ventilation (HFV) are often performed under conditions of controlled mean airway pressure (Paw). In the present study we tested the assumption that controlling Paw adequately controls lung volume during HFV by investigating the relationship between a reliably measured Paw and the mean alveolar pressure (Palv) of the lungs during HFV of healthy dogs. We minimized the errors of Paw measurement due to the Bernoulli effect and various technical factors by appropriate choice of transducers, amplifiers, and measurement site. Palv was estimated by clamping the ventilator tube during oscillation and measuring the equilibration pressure of the lung and airways. Paw and Palv were determined as functions of frequency (8-25 Hz), tidal volume (60-90 ml), Paw (-5 to 12 cmH2O), and position of the animal (supine vs. lateral). We found that Paw could significantly underestimate Palv and that the degree of underestimation increased at higher frequencies, larger tidal volumes, and lower Paw. Shifting the animal from the supine to the lateral position greatly accentuated this effect. The elevation of Palv above Paw was seen to be a function of mean flow and largely independent of the frequency-tidal volume combination which produced the flow. A possible explanation of this pressure difference is that it results from differences in inspiratory and expiratory airway impedances, which in turn depend on airway geometry, compliance, lung volume, and expiratory flow limitation.

Airway Resistance↗
PubMed1983

A re-evaluation of the hemodynamic consequences of intermittent positive pressure ventilation.

The hemodynamic effects of intermittent positive pressure ventilation (IPPV) have generally been considered straightforward, being dominated by the inspiratory reduction in systemic venous return. Paradoxically, there is considerable debate regarding the effects of PEEP. We have studied both right ventricular (RV) and left ventricular (LV) performance during a single IPPV respiratory cycle in dogs with intact circulatory systems or the right heart bypassed in open and closed chest conditions. We have found that the "reverse pulsus paradoxus" during inspiration reflects both transmission of the increased intrathoracic pressure to the thoracic aorta and an increase in LV stroke volume (SV). This inspiratory increase in LVSV has been found to be influenced by, but not dependent on: (a) respiratory variations in RVSV; (b) variations in functional residual capacity or tidal volume altering pulmonary venous return and the degree of physical compression of the heart by the lungs; (c) an inspiratory decrease in RV volume, increasing LV diastolic compliance and, thus, probably improving pulmonary venous return; (d) a decreased transmural aortic diastole pressure reflecting an effective decrease in LV afterload produced by both the general increase in intrathoracic pressure and the direct compression of the heart; and (e) variations in the pulmonary vascular volume as indicated by changes in the transmural LV end-diastolic pressure. An understanding of IPPV during a single respiratory cycle facilitates an appreciation of the steady state hemodynamic effects of IPPV with or without PEEP. Our results imply that measurements made only at end-expiration, ignoring inspiratory events, may have serious limitations. Furthermore, they suggest that IPPV with PEEP should be evaluated as a form of LV assist in LV failure.

Animals↗
PubMed1983

Hypoxic constriction of alveolar and extra-alveolar vessels in isolated pig lungs.

To examine whether hypoxia causes constriction of alveolar or extra-alveolar vessels, we determined the relationships among transpulmonary pressure, pulmonary arterial pressure (Ppa), blood flow (Q), and transvascular fluid filtration rate (W) during normoxia (PO2 = 200 Torr) and hypoxia (PO2 = 50 Torr) in isolated pig lungs perfused with autologous blood. Left atrial pressures were always subatmospheric. The effects of lung inflation and hypoxic vasoconstriction on the Ppa-Q relationship were similar; when transpulmonary pressure was greater than 5 Torr, both shifted the curve to higher pressures in a parallel fashion. When transpulmonary pressure was 0-5 Torr, however, inflation had no effect on the Ppa-Q relationship during either normoxia or hypoxia. During normoxia at a transpulmonary pressure of 3.5 Torr, the relationship between fluid filtration rate and flow was characterized by a W of zero at Q less than 1.5 l/min and a rapid increase in W with Q above this value. Both hypoxia and inflation shifted this relationship to higher filtration rates in a parallel fashion. Furthermore, the combined effects of hypoxia and inflation on filtration rate were additive. These results suggest that hypoxia caused constriction of both alveolar and extra-alveolar vessels, resulting in increased intraluminal pressure and filtration of fluid in vessels upstream from the sites of constriction.

Animals↗
PubMed1983

Elastic characteristics of the lung perivascular interstitial space.

An analysis of the elastic behavior of the lung perivascular interstitial space during interstitial fluid accumulation is presented. Fluid accumulation must deform the lung parenchyma and vascular walls that form the interstitial space boundaries. The deformations of these boundaries are predicted from previously published data on the elastic properties of the boundary materials. The analysis gives the relationships among the elastic properties of the boundaries, the compliance of the interstitium, the lung volume, and the lung elastic recoil pressure. Values of the interstitial compliance are predicted to decrease with increasing lung recoil pressure and are dependent on the lung pressure-volume history. At low recoil pressures over 70% of the interstitial compliance results from deformation of the parenchyma. As the recoil pressure increases, either with increasing lung volume or due to the lung pressure-volume history, the contributions of the parenchymal and vascular wall deformations become similar. The predictions are generally consistent with published data on interstitial compliance obtained from measurements of isolated lung weight gain during vascular fluid transudation. This correlation suggests that the elastic behavior of the interstitial space can be accounted for by the known elastic properties of the boundary materials.

Animals↗
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↗