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Biomedical subjects

R D Hubmayr

Publications and source records attributed to R D Hubmayr.

At least 19 recordsLinked to original sources
PubMed2001

Viscoelastic properties of the human colon.

Our objectives were to characterize colonic viscoelastic properties of the human descending colon by assessing pressure-volume (P-V) relationships during barostatic balloon distension. In 16 healthy subjects, a balloon was inflated to 44 mmHg and then deflated to 0 mmHg in 4-mmHg steps at 10, 30, and 60 ml/min, allowing volume fluctuations to stabilize at each pressure increment. Thereafter, these "quasi-static" P-V curves were compared with "dynamic" distensions to 300 ml, at 1 and 10 ml/s, before and after intravenous atropine in another five subjects. During quasi-static curves, balloon volume stabilized at each pressure increment. Quasi-static P-V curves were reproducible within individuals and approximated to a power exponential function and revealed hysteresis, indicative of viscoelasticity. Body mass index influenced quasi-static P-V curves during inflation but not during deflation. The colon was less compliant during dynamic distensions at 10 ml/s than during quasi-static distensions. Atropine increased quasi-static compliance and attenuated differences between quasi-static and rapid distensions. We conclude that colonic viscoelastic properties can be assessed by quasi-static P-V curves. Rapid colonic distension activated neural reflexes, thereby reducing colonic compliance compared with quasi-static distensions.

Adult↗
PubMed2001

Deformation-induced lipid trafficking in alveolar epithelial cells.

Mechanical ventilation with a high tidal volume results in lung injury that is characterized by blebbing and breaks both between and through alveolar epithelial cells. We developed an in vitro model to simulate ventilator-induced deformation of the alveolar basement membrane and to investigate, in a direct manner, epithelial cell responses to deforming forces. Taking advantage of the novel fluorescent properties of BODIPY lipids and the fluorescent dye FM1-43, we have shown that mechanical deformation of alveolar epithelial cells results in lipid transport to the plasma membrane. Deformation-induced lipid trafficking (DILT) was a vesicular process, rapid in onset, and was associated with a large increase in cell surface area. DILT could be demonstrated in all cells; however, only a small percentage of cells developed plasma membrane breaks that were reversible and nonlethal. Therefore, DILT was not only involved in site-directed wound repair but might also have served as a cytoprotective mechanism against plasma membrane stress failure. This study suggests that DILT is a regulatory mechanism for membrane trafficking in alveolar epithelia and provides a novel biological framework within which to consider alveolar deformation injury and repair.

Boron Compounds↗
PubMed2001

Mechanisms of recruitment in oleic acid-injured lungs.

Lung recruitment strategies, such as the application of positive end-expiratory pressure (PEEP), are thought to protect the lungs from ventilator-associated injury by reducing the shear stress associated with the repeated opening of collapsed peripheral units. Using the parenchymal marker technique, we measured regional lung deformations in 13 oleic acid (OA)-injured dogs during mechanical ventilation in different postures. Whereas OA injury caused a marked decrease in the oscillation amplitude of dependent lung regions, even the most dependent regions maintained normal end-expiratory dimensions. This is because dependent lung is flooded as opposed to collapsed. PEEP restored oscillation amplitudes only at pressures that raised regional volumes above preinjury levels. Because the amount of PEEP necessary to promote dependent lung recruitment increased the end-expiratory dimensions of all lung regions (nondependent AND dependent ones) compared with their preinjury baseline, the "price" for recruitment is a universal increase in parenchymal stress. We conclude that the mechanics of the OA-injured lung might be more appropriately viewed as a partial liquid ventilation problem and not a shear stress and airway collapse problem and that the mechanisms of PEEP-related lung protection might have to be rethought.

Animals↗
PubMed2001

Mechanics of edematous lungs.

Using the parenchymal marker technique, we measured pressure (P)-volume (P-V) curves of regions with volumes of approximately 1 cm3 in the dependent caudal lobes of oleic acid-injured dog lungs, during a very slow inflation from P = 0 to P = 30 cmH2O. The regional P-V curves are strongly sigmoidal. Regional volume, as a fraction of volume at total lung capacity, remains constant at 0.4-0.5 for airway P values from 0 to approximately 20 cmH2O and then increases rapidly, but continuously, to 1 at P = approximately 25 cmH2O. A model of parenchymal mechanics was modified to include the effects of elevated surface tension and fluid in the alveolar spaces. P-V curves calculated from the model are similar to the measured P-V curves. At lower lung volumes, P increases rapidly with lung volume as the air-fluid interface penetrates the mouth of the alveolus. At a value of P = approximately 20 cmH2O, the air-fluid interface is inside the alveolus and the lung is compliant, like an air-filled lung with constant surface tension. We conclude that the properties of the P-V curve of edematous lungs, particularly the knee in the P-V curve, are the result of the mechanics of parenchyma with constant surface tension and partially fluid-filled alveoli, not the result of abrupt opening of airways or atelectatic parenchyma.

Air Pressure↗
PubMed2001

Validation of a new live cell strain system: characterization of plasma membrane stress failure.

Motivated by our interest in lung deformation injury, we report on the validation of a new live cell strain system. We showed that the system maintains a cell culture environment equivalent to that provided by conventional incubators and that its strain ouput was uniform and reproducible. With this system, we defined cell deformation dose (i.e., membrane strain amplitude)-cell injury response relationships in alveolar epithelial cultures and studied the effects of temperature on them. Deformation injury occurred in the form of reversible, nonlethal plasma membrane stress failure events and was quantified as the fraction of cells with uptake and retention of fluorescein-labeled dextran (FITC-Dx). The undeformed control population showed virtually no FITC-Dx uptake at any temperature, which was also true for cells strained by 3%. However, when the membrane strain was increased to 18%, ~5% of cells experienced deformation injury at a temperature of 37 degrees C. Moreover, at that strain, a reduction in temperature to 4 degrees C resulted in a threefold increase in the number of cells with plasma membrane breaks (from 4.8 to 15.9%; P < 0.05). Cooling of cells to 4 degrees C also lowered the strain threshold at which deformation injury was first seen. That is, at a 9% substratum strain, cooling to 4 degrees C resulted in a 10-fold increase in the number of cells with FITC-Dx staining (0.7 vs. 7.5%, P < 0.05). At that temperature, A549 cells offered a 50% higher resistance to shape change (magnetic twisting cytometry measurements) than at 37 degrees C. We conclude that the strain-injury threshold of A549 cells is reduced at low temperatures, and we consider temperature effects on plasma-membrane fluidity, cytoskeletal stiffness, and lipid trafficking as responsible mechanisms.

Cell Division↗
PubMed2001

Mechanical properties of alveolar epithelial cells in culture.

With the use of magnetic twisting cytometry, we characterized the mechanical properties of rat type II alveolar epithelial (ATII) cells in primary culture and examined whether the cells' state of differentiation and the application of deforming stresses influence their resistance to shape change. Cells were harvested from rat lungs as previously described (Dobbs LG. Am J Physiol Lung Cell Mol Physiol 258: L134-L147, 1990) and plated at a density of 1 x 10(6) cells/cm(2) in fibronectin-coated 96 Remova wells, and their mechanical properties were measured 2-9 days later. We show 1) that ATII cells form much stronger bonds with RGD-coated beads than they do with albumin- or acetylated low-density lipoprotein-coated beads, 2) that RGD-mediated bonds seemingly "mature" during the first 60 min of bead contact, 3) that the apparent stiffness of ATII cells increases with days in culture, 4) that stiffness falls when the RGD-coated beads are intermittently oscillated at 0.3 Hz, and 5) that this fall cannot be attributed to exocytosis-related remodeling of the subcortical cytoskeleton. Although the mechanisms of force transfer between basement membrane, cytoskeleton, and plasma membrane of ATII cells remain to be resolved, such analyses undoubtedly require definition of the cell's mechanical properties. To our knowledge, the results presented here provide the first data on this topic.

Animals↗
PubMed2000

Invited review: plasma membrane stress failure in alveolar epithelial cells.

In this review, we examine the hypothesis that plasma membrane stress failure is a central event in the pathophysiology of injury from alveolar overdistension. This hypothesis leads us to consider alveolar micromechanics and specifically the mechanical interactions between lung matrix and alveolar epithelial cell cytoskeleton and plasma membrane. We then explore events that are central to the regulation of plasma membrane tension and detail the lipid-trafficking responses of in vitro deformed and/or injured cells. We conclude with a reference to upregulation of stress-responsive genes after membrane injury and resealing.

Animals↗
PubMed2000

The prone position eliminates compression of the lungs by the heart.

The prone position improves gas exchange in many patients with ARDS. Animal studies have indicated that turning prone restores ventilation to dorsal lung regions without markedly compromising ventral regions. To investigate a potential mechanism by which this might occur, the relative volume of lung located directly under the heart was measured in the supine and prone positions in seven patients. Four axial tomographic sections between the carina and the diaphragm were analyzed (Sections 1 through 4). When supine, the percent of the total lung volume located under the heart increased from 7 +/- 4% to 42 +/- 8%, and from 11 +/- 4% to 16 +/- 4% in Sections 1 through 4, in the left and right lungs, respectively. When prone, the percent of left and right lung volume located under the heart was </= 1 and </= 4 %, respectively, in all four sections (p < 0.05 for each section, supine versus prone). Although a large fraction of the lung, particularly on the left, is located directly under the heart in supine patients, and would be subject to the compressive force resulting from heart weight, almost no lung is located under the heart when patients are prone and the compressive force of the heart is directed towards the sternum.

Adult↗
PubMed1999

Stretch induces cytokine release by alveolar epithelial cells in vitro.

Mechanical ventilation can injure the lung, causing edema and alveolar inflammation. Interleukin-8 (IL-8) plays an important role in this inflammatory response. We postulated that cyclic cell stretch upregulates the production and release of IL-8 by human alveolar epithelium in the absence of structural cell damage or paracrine stimulation. To test this hypothesis, alveolar epithelial cells (A549 cells) were cultured on a deformable silicoelastic membrane. When stretched by 30% for up to 48 h, the cells released 49 +/- 34% more IL-8 (P < 0.001) than static controls. Smaller deformations (20% stretch) produced no consistent increase in IL-8. Stretch of 4 h duration increased IL-8 gene transcription fourfold above baseline. Stretch had no effect on cell proliferation, cell viability as assessed by (51)Cr release assay, or the release of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha. We conclude that deformation per se can trigger inflammatory signaling and that alveolar epithelial cells may be active participants in the alveolitis associated with ventilator-induced lung injury.

Blotting, Northern↗
PubMed1999

Regional expansion of oleic acid-injured lungs.

It has been suggested that dependent regions of an injured lung are collapsed and subject to cyclic reopening and collapse during mechanical ventilation. To test this hypothesis, we measured both temporal and spatial heterogeneity of lobar expansion in oleic acid (OA)-injured dogs. Regional volumes were measured in nine dogs (seven supine and two prone) during closed loop sinusoidal oscillations of the lungs before and after OA injury using the parenchymal marker technique. In contrast to computer tomography, the parenchymal marker technique provides absolute measures of regional tissue dimensions as opposed to relative measures of regional air to liquid content. The experiments generated three major findings: (1) OA injury did not lead to the collapse of dependent lung units at FRC, (2) OA injury did not steepen the vertical gradient in regional lung volumes at FRC, and (3) during sinusoidal oscillation of the OA-injured lungs from FRC, dependent regions did not undergo cyclic reopening and collapse. On the basis of these results, we propose an alternative mechanism for the topographic variability in regional impedances and lung expansion after injury, namely liquid and foam in conducting airways.

Animals↗
PubMed1999

Entrainment of respiration in humans by periodic lung inflations. Effect of state and CO(2).

Lack of synchrony between a patient and the mechanical ventilator occurs when the respiratory rhythm of the patient fails to entrain to machine inflations. Entrainment implies a resetting of the respiratory rhythm such that a fixed temporal relationship exists between the onset of inspiratory activity and the onset of a mechanical breath. We examined the entrainment response to mechanical ventilation of normal humans over a range of machine rates during wakefulness and during isocapnic and hypercapnic NREM sleep. Wakefulness facilitated 1:1 entrainment of the respiratory rhythm to the mechanical ventilator over a wider range of machine frequencies than during NREM sleep (p < 0.001); isocapnic and hypercapnic conditions did not differ (p = 0.95). To evaluate the Hering-Breuer reflexes in the resetting of the respiratory rhythm during sleep, we examined changes in neural inspiratory time (TI) as the relationship between inspiratory efforts and onset of machine inflations changed. As inspiratory efforts extended into the machine inflation cycle, neural TI shortened. We conclude that entrainment responses of normal humans to mechanical ventilation differ depending on state, but mild increases in respiratory drive caused by CO(2) stimulation do not affect these entrainment responses. Furthermore, the changes in neural TI are consistent with observations in animal studies in which Hering-Breuer reflexes mediated entrainment.

Adult↗
PubMed1998

Lung volume reduction surgery for emphysema: out on a limb without a NETT.

Lung volume reduction surgery (LVRS) has recently been rediscovered and offers the potential of improving the quality of life of patients with advanced emphysema. In this article, we discuss the historical and contemporary versions of LVRS. Although initial enthusiasm has been substantial, existing data seem insufficient to demonstrate the safety and efficacy of the procedure in comparison with conventional medical therapy. Fundamental questions remain regarding the long-term effects of an operation versus medical therapy, the optimal selection criteria, the best measures of efficacy, the mechanisms of improvement, the cost-effectiveness of the procedure, and the optimal surgical technique. Until such questions are answered, advising patients about the best management their emphysema will be difficult. The National Emphysema Treatment Trial will address many of these issues and should be embraced by both health-care providers and patients.

Forced Expiratory Volume↗
PubMed1998

Patient-ventilator interactions.

The focus of this chapter has been the information contained in airway pressure, volume, and flow traces from mechanically-ventilated patients. It has not been our intention to make ventilator management recommendations. Practitioners willing to make the effort to interpret patient-ventilator interactions will find it difficult to manage ventilator-dependent patients without feedback from waveform analysis in the future.

Airway Resistance↗