Biomedical subjects
M A Schroeder
Publications and source records attributed to M A Schroeder.
A clinical pathway for congestive heart failure.
This study has shown improved outcomes with the use of a clinical pathway. However, under PPS additional ways for coordination among healthcare providers and patients need to be developed to ensure improved care beyond those focusing on the use of the pathway. One recommendation is the use of telehealth.
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.
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.
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.
Predictors of hospital readmission among the elderly with congestive heart failure.
This study compared elderly patients with congestive heart failure discharged from home healthcare to the home vs. those rehospitalized. The rate of rehospitalization in this sample of 117 was 27%. Significant predictors of rehospitalization included number of home healthcare days, number of previous hospitalizations, and the services of a home health aide. Implications include the timing and nature of home health visits.
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.
Major influences on maternal responsiveness to infants.
Thirty healthy, middle-class mothers were interviewed during their postpartum hospital stay to identify major influences on mothers' responses to their infants. Sullivan's theorem of tenderness served as a guide for exploring maternal responsiveness. Three major categories, infant tenderness needs, maternal perception, and maternal needs, and their related properties, were described. Support persons were viewed as very important. Mothers also believed that some infant needs were more important than others. Finally, mothers felt that they were constantly faced with priorities, and that the emotional state of the mother and infant often influenced their interaction.
Regional adaptations of rabbit diaphragm muscle fibers to unilateral denervation.
We hypothesized that adaptations of the rabbit diaphragm (Dia) after unilateral denervation (DNV) result from removal of a neural influence rather than from passive stress. Length changes of midcostal and sternal Dia regions were measured before and after DNV by using sonomicrometry. Midcostal fibers passively lengthened after DNV, whereas sternal fibers shortened. In both regions, these length changes were associated with minimal stress, as estimated from passive force-length relationships. Morphological and contractile adaptions of midcostal and sternal Dia regions were examined after 1 and 4 wk of DNV. In both Dia regions, type I fibers progressively hypertrophied, whereas type IIb fibers atrophied. After DNV, changes in isometric contraction were similar in both Dia regions. Twitch contraction and half-relaxation times increased, force-frequency relationships shifted leftward, and maximum tetanic force decreased. We conclude that passive length changes and mechanical stress are not the main determinants of the morphological and contractile adaptations of the Dia after unilateral DNV but that these adaptations result from DNV itself.
Achieving network-wide integration.
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Experimental emphysema.
This animal model of emphysema exhibits the same abnormalities in respiratory mechanics as those seen in human emphysema. The histologic and radiographic findings also closely resemble changes of panacinar disease. Moreover, the progressive hypoxemia preceding hypercarbia also parallels the clinical course seen in human disease. Drawbacks of this model include the long time period required to develop significant changes and the cost of maintaining the animals for such a time period. Large cystic areas were not noted in our animals and one would have to turn to another model to address the problem of giant bullous emphysema. There is no ideal animal model of pulmonary emphysema, and the usefulness of an experimental model should be judged on how well it answers the specific questions. Significant information has been obtained using various animal models of emphysema in lung transplantation, diaphragmatic function, pulmonary hemodynamics, and in several other areas. The dog appears to be a suitable model for thoracic surgical research on emphysema.
Functional significance of expiratory muscles during spontaneous breathing in anesthetized dogs.
Recent electromyographic studies in awake and anesthetized dogs have demonstrated that spontaneous breathing in prone dogs is associated with an increased activation of the expiratory muscles compared with that recorded in supine dogs. On the basis of these observations, one would infer that the mechanical role and contribution of the expiratory musculature to the act of breathing are enhanced in the prone posture. The changes in length associated with these postural increases in expiratory muscle electrical activity, however, have not been investigated and formed the basis of our investigation. We examined the active and passive changes in length of expiratory muscles during spontaneous breathing in supine and prone anesthetized dogs and assessed the relative role of the expiratory musculature in the generation of tidal volume. The experiments were performed on eight mongrel dogs anesthetized with pentobarbital sodium. In all eight animals, spontaneous breathing in the prone posture was associated with an increased activation (electromyogram) of the triangularis sterni, external oblique, and transversus abdominis muscles compared with that recorded in the supine posture. We quantitated the role of the expiratory muscles in both postures by measuring the volume difference between relaxation volume of the respiratory system and the end-expiratory lung volume. In the supine animal, 93 ml were attributed to the expiratory musculature, whereas in the prone animal, we noted that 186 ml (P < 0.01) were displaced during expiration, representing 43 and 52% (NS) of tidal volume, respectively. During spontaneous breathing in the supine or prone posture, all three expiratory muscles underwent significant length changes.(ABSTRACT TRUNCATED AT 250 WORDS)
Static lung-lung interactions in unilateral emphysema.
Motivated by the introduction of single-lung transplantation into clinical practice, we compared the static mechanical properties of the respiratory system in six supine dogs before (at baseline) with those after the induction of unilateral emphysema. Relaxation volume (Vrel), total lung capacity (TLC), and static compliance of the emphysematous lung increased to 214 +/- 68, 186 +/- 39, and 253 +/- 95% (SD) of baseline, respectively. Vrel of the nonemphysematous lung fell to 81 +/- 28% of baseline, with no significant change in TLC of the nonemphysematous lung or its pressure-volume relationship, indicating that unilateral hyperinflation does not cause dropout of contralateral lung units. After unilateral emphysema, the chest wall shifted to a higher unstressed or neutral volume (when pleural pressure equals atmospheric pressure) in three of six animals, minimizing the anticipated decrease in lung recoil pressure at the higher respiratory system Vrel. The pattern of relative lung emptying in the intact dog and in the excised lungs was similar during stepwise deflations from TLC, suggesting that mean pleural pressure of the hemithoraces is equal. We conclude that in the dog the static volume distribution between emphysematous and nonemphysematous lungs is determined only by differences in lung recoil and compliance.
Mechanical role of expiratory muscle recruitment during eupnea in supine anesthetized dogs.
To assess the mechanical role of the expiratory musculature during eupnea, we recorded the electromyographic (EMG) activity of the triangularis sterni, the external oblique, and the transversus abdominis in eight supine lightly anesthetized dogs and have measured the volume generated by the phasic activation of the expiratory muscles. Activation of the expiratory muscles was invariably associated with a decrease in lung volume below the relaxed position of the respiratory system, a volume equal to 41.3 +/- 8.4 ml. This volume represented roughly 20% of tidal volume generated during spontaneous breathing. The fractional expiratory contribution to the tidal volume was unrelated to the size of the animal. Traction on the forelimbs (limb extension), however, tended to enhance the phasic expiratory activation of both the triangularis sterni and the transversus abdominis in the majority of animals. Moreover, after limb extension, the fractional contribution of tidal volume attributed to the phasic activation of the expiratory muscles increased in all but one animal. During spontaneous breathing with the forelimbs extended, roughly 25% of tidal volume was found to be due directly to phasic expiratory muscle contraction. The present observations firmly establish that in supine lightly anesthetized dogs breathing at rest the expiratory component of tidal volume represents a substantial contribution.
Mechanical role of expiratory muscles during breathing in prone anesthetized dogs.
The purpose of the present study was to assess the mechanical role of the expiratory muscles during spontaneous breathing in prone animals. The electromyographic (EMG) activity of the triangularis sterni, the rectus abdominis, the external oblique, and the transversus abdominis was studied in 10 dogs light anesthetized with pentobarbital sodium. EMGs were recorded during spontaneous steady-state breathing in supine and prone suspended animals both before and after cervical vagotomy. We also measured the end-expiratory lung volume [functional residual capacity (FRC)] in supine and prone positions to assess the mechanical role of expiratory muscle activation in prone dogs. Spontaneous breathing in the prone posture elicited a significant recruitment of the triangularis sterni, the external oblique, and the transversus abdominis (P less than 0.05). Bilateral cervical vagotomy eliminated the postural activation of the external oblique and the transversus abdominis but not the triangularis sterni. Changes in posture during control and after cervical vagotomy were associated with an increase in FRC. However, changes in FRC, on average, were 132.3 +/- 33.8 (SE) ml larger (P less than 0.01) postvagotomy. We conclude that spontaneous breathing in prone anesthetized dogs is associated with a marked phasic expiratory recruitment of rib cage and abdominal muscles. The present data also indicate that by relaxing at end expiration the expiratory muscles of the abdominal region are directly responsible for generating roughly 40% of the tidal volume.
Diagnosing and dealing with multicollinearity.
The purpose of this article was to increase nurse researchers' awareness of the effects of collinear data in developing theoretical models for nursing practice. Collinear data distort the true value of the estimates generated from ordinary least-squares analysis. Theoretical models developed to provide the underpinnings of nursing practice need not be abandoned, however, because they fail to produce consistent estimates over repeated applications. It is also important to realize that multicollinearity is a data problem, not a problem associated with misspecification of a theorectical model. An investigator must first be aware of the problem, and then it is possible to develop an educated solution based on the degree of multicollinearity, theoretical considerations, and sources of error associated with alternative, biased, least-square regression techniques. Decisions based on theoretical and statistical considerations will further the development of theory-based nursing practice.
Effect of midline laparotomy on the cough reflex in dogs.
The present studies were designed to test the hypothesis that midline laparotomy promotes selective inhibition of the transversus abdominis muscle during cough as it does during expiratory threshold loading. Anesthetized dogs were studied in the supine posture, and cough was induced by mechanical stimulation of the airways. Midline laparotomy had virtually no effect on the cough-induced activation of the triangularis sterni or the external oblique. On the other hand, the activation of the transversus abdominis was markedly reduced in all animals. Despite this marked inhibition, however, peak pleural pressure and expiratory flow were preserved. This suggests that this inhibition does not play a significant role in determining the occurrence of bronchopulmonary infection after abdominal surgery.
Canine model of chronic bronchial injury. Lung mechanics and pathologic changes.
Bronchial injury was induced in 7 dogs by exposure to nebulized 1% nitric acid 3 days per week for 4 weeks. Lung mechanics were measured prior to exposure, at the completion of exposure, and at 1, 3, and 5 months postexposure. Airway obstruction persisted unabated throughout the postexposure period, with significant reductions in maximal expiratory flows. Pulmonary resistance, the slope of phase III, and the volume of isoflow were increased. Hyperresponsiveness to histamine developed between 3 and 5 months. Histologically, there was minimal damage to the cartilaginous airways. Widespread chronic inflammation with minimal fibrosis was seen in the membranous bronchi and respiratory bronchioles. Pathology scores for cartilaginous and noncartilaginous (small) airways were developed and correlated with tests of airway function. Small airways pathology scores correlated with flows at 50 and 25% of the vital capacity and with pulmonary resistance. Density dependence of maximal expiratory flow, closing volume, and closing capacity failed to correlate with either the airway obstruction or the small airways pathology scores.