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R D Hubmayr

Publications and source records attributed to R D Hubmayr.

At least 19 recordsLinked to original sources
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↗
PubMed1997

The determinants of respiratory rate during mechanical ventilation.

The independent and interactive effect of feedback related to volume, CO2, inspiratory flow, and arousal state on the regulation of respiratory rate in mechanically ventilated humans is not well characterized. We examined the rate response of eight normal volunteers during both quiet wakefulness and non-rapid-eye-movement (NREM) sleep, while mechanically ventilated through a nasal mask in an assist/control mode with a machine back-up rate of 2 breaths/min. Tidal volume (VT) was set slightly above spontaneous VT and then increased by 0.2 L every 3 min up to 1.8 L or 25 ml/kg. Either an inspiratory flow of 40 L/min or an inspiratory time of 2 s (iso-T(I)) was set, with CO2 added (F(I)CO2 > 0) or F(I)CO2 = 0. Measurements were made during both quiet wakefulness and NREM sleep. We found that as VT increased, the respiratory rate decreased; the rate decline was observed during wakefulness and sleep, and under isocapnic as well as hypocapnic conditions. Increasing inspiratory flow raised the respiratory rate during wakefulness and NREM sleep. During NREM sleep, hypocapnia resulted in wasted ventilator trigger efforts. In summary, both VT and inspiratory flow settings affect the respiratory rate, and depending on state, can affect CO2 homeostasis. Ventilator settings appropriate for wakefulness may cause ventilatory instability during sleep.

Adolescent↗
PubMed1997

The Mayo Ventilator-Dependent Rehabilitation Unit: a 5-year experience.

OBJECTIVE: To describe the outcomes of 206 patients admitted to the Mayo Ventilator-Dependent Rehabilitation Unit (VDRU) during a 5-year study period. DESIGN: We analyze the patient data for 1990 through 1994, which had been prospectively entered into a computer database for a cohort of 206 patients who had become ventilator dependent during their current hospitalization. MATERIAL AND METHODS: Patients in the VDRU were classified into one of six categories that reflected the reasons for ventilator dependence. Ability to be weaned from mechanical ventilation, duration of hospital stay and ventilator dependence, outcome, disposition, demographics, and long-term survival were analyzed. The VDRU patient group was compared for hospital and follow-up outcomes with a group of historical control patients previously described by us. RESULTS: The Mayo VDRU was established in January 1990. During the first 5 years of its operation, 206 newly ventilator-dependent patients were admitted to the VDRU, 190 (92%) of whom survived to be dismissed; 16 patients (8%) died in the hospital. Of the 190 patients dismissed, 77% were able to return to their homes. Overall, 153 patients were liberated from mechanical ventilation, whereas 37 remained either completely or partially ventilator dependent. Of these 37 patients, 27 (73%) were receiving nocturnal mechanical ventilation only. The 4-year survival was 53%. CONCLUSION: The Mayo VDRU has been highly successful in liberating newly ventilator-dependent patients from mechanical ventilation. The long-term survival after management in the VDRU has been excellent. In addition, the medical charges for care in the VDRU are less than intensive-care unit charges.

Adolescent↗
PubMed1996

Pharmacological activation changes stiffness of cultured human airway smooth muscle cells.

Using magnetic twisting cytometry (MTC), we measured the cytoskeletal stiffness of adherent human airway smooth muscle (HASM) cells. We hypothesized that modulation of actin-myosin interactions by application of contractile agonists would induce changes in cytoskeletal stiffness. In cells plated on high-density collagen, bradykinin (10(-6) M) and histamine (10(-4) M) increased stiffness by 85 +/- 15 and 68 +/- 16%, respectively. Increases in cell stiffness were also consistently observed after acetylcholine, substance P, and KCl. The bronchodilator agonists isoproterenol, prostaglandin E2, forskolin, dibutryl adenosine 3', 5'-cyclic monophosphate, and 8-bromoguanosine 3', 5'-cyclic monophosphate each caused a dose-dependent decrease in cell stiffness in unstimulated as well as bradykinin-treated cells. HASM cells plated on high-density collagen were stiffer than cells plated on low-density collagen (126 +/- 16 vs. 43 +/- 3 dyn/cm2) and developed more pronounced increases in stiffness in response to bradykinin as well as more pronounced decreases in stiffness in response to isoproterenol. These results are consistent with the hypothesis that modulation of actin-myosin interactions by application of contractile agonists causes changes in cytoskeletal stiffness of HASM cells. MTC may be a valuable tool for evaluating the mechanisms of pharmacomechanical coupling in airway smooth muscle cells in culture.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Nonuniform expansion of constricted dog lungs.

The parenchymal marker technique was used to measure regional tidal volumes of samples of lung parenchyma in four open-chest supine dogs. Radiopaque markers that had been implanted in the lower lobe were tracked by biplane video fluoroscopy during sinusoidal volume oscillations at tidal volumes of approximately 20% of total lung capacity and frequencies of 1-40 breaths/min before and after methacholine was administered by aerosol. The volumes of tetrahedrons with apexes at four markers were computed, and sine waves were fit to the data for volume vs. time for each tetrahedron. The ratio of mean regional volume to mean airway pressure decreased by 10-45% after exposure to methacholine. Dynamic lung elastance and resistance of the constricted lungs were larger than control, and both were frequency dependent. Regional elastance and resistance varied considerably among tetrahedrons, and these were also frequency dependent. The data were fit by a model in which tissue elastance was uniform and nearly equal to elastance in the control state, but small-airway resistance was high and variable. We conclude that the lung contracts under bronchoconstriction but that the increased dynamic elastance and resistance of the constricted lung may be primarily the result of nonuniform increased airway resistance at the level of the terminal bronchioles.

Air Pressure↗
PubMed1996

Regional lung volume trajectories during expiratory flow in dogs.

Parenchymal markers were placed in the left caudal lobes of anesthetized dogs, and the three-dimensional positions of the markers were tracked by biplane videofluoroscopy during expiration from total lung capacity (TLC) to approximately 30% TLC at steady expiratory flows of 0.3-7% TLC/s. Regional volumes of samples of parenchyma with volumes at TLC of 1-5 cm3 were obtained by computing the volumes of tetrahedral defined by taking the markers, four at a time, as apices of the tetrahedra, Regional volume (Vr), as a fraction of volume at TLC, was plotted against average volume (VL), as a fraction of volume at TLC, and Vr was fit by a quadratic function of VL. The initial slopes of the plots, dVr/dVL at VL = 1, varied by +/- 26% from the mean slope of 1. The curvatures were highly correlated with the slopes, and the Vr vs. VL plots formed a nest of "onion skins". The initial slopes were weakly correlated with the vertical position of the centroid of the tetrahedron, with the slope increasing by approximately 20%/cm, on average, in the dorsal direction in the supine dog. The vertical gradient in Vr accounted for approximately 30% of the total variability; small-scale heterogeneity contributed the remaining 70%. These results confirm earlier quasistatic measurements of nonuniform Vr and provide the first data on curvature of Vr trajectories. The mechanisms that cause the nongravitational component of Vr variability and the curvatures of the trajectories are unknown.

Animals↗
PubMed1996

Regional ventilation in statically and dynamically hyperinflated dogs.

Using the parenchymal marker technique in normal anesthetized dogs, we compared the dynamics of regional lung expansion between two ventilation strategies designed to increase mean thoracic volume. Dynamic hyperinflation (DH was produced by ventilating the lungs at a rate of 50 breaths/min and with a duty cycle of 0.5. Static hyperinflation (SH) was produced through the application of extrinsic positive end-expiratory pressure while the lungs were ventilated at a rate of 15 breaths/min and with a duty cycle of 0.15. Regional tidal volume (VT,r), regional functional residual volume, and the time delay between regional expansion and the flow signal at the common airway were computed for up to 100 regions/lobe in 5 animals. Ventilation strategy had no effect on the overall variance of VT,r within lobes. Although the VT,r measured during SH correlated with VT,r measured during DH, the average correlation coefficient was only 0.69. Ventilation rate-related differences in VT,r and regional functional residual capacity varied with the regional time delay in ways qualitatively consistent with parallel inhomogeneity of unit time constants. However, a large component of frequency-dependent behavior remains unexplained by established mechanisms. We conclude that DH and SH should not be considered equivalent lung unit recruitment strategies.

Animals↗
PubMed1996

Efficacy of nocturnal nasal ventilation in stable, severe chronic obstructive pulmonary disease during a 3-month controlled trial.

OBJECTIVE: To evaluate the efficacy of nocturnal nasal ventilation (NNV) in patients with rigidly defined, severe but stable chronic obstructive pulmonary disease (COPD) and hypercapnia. DESIGN: By randomization, eligible patients were assigned to an active or a sham treatment arm. Data from these two groups were analyzed statistically. MATERIAL AND METHODS: Initially, 35 patients with severe COPD (forced expiratory volume in 1 second [FEV1] of less than 40% predicted) and daytime hypercapnia (arterial carbon dioxide tension [PaCO2] of more than 45 mm Hg) were enrolled in a 3-month NNV trial. After a minimal observation period of 6 weeks, 13 patients were judged to be clinically stable and were randomized to NNV (N = 7) or sham (N = 6) treatment, consisting of nightly use of a bilevel positive airway pressure (PAP) device set to deliver an inspiratory pressure of either 10 or 0 cm of water (H2O). The device was used in the spontaneous or timed mode and set to a minimal expiratory pressure of 2 cm H2O. Patients underwent extensive physiologic testing including polysomnography and were introduced to the bilevel PAP system during a 2.5-day hospital stay. RESULTS: The NNV and sham treatment groups were similar in mean age (71.0 versus 66.5 years), PaCO2 (54.7 versus 48.5 mm Hg), and FEV1 (0.62 versus 0.72 L). Only four of seven patients in the NNV group were still using the bilevel PAP device at the completion of the trial, as opposed to all six patients in the sham group. Only one patient had a substantial reduction in PaCO2 - from 50 mm Hg at baseline to 43 mm Hg after 3 months of NNV. He declined further NNV treatment with bilevel PAP. Sham treatment did not lower PaCO2. Lung function, nocturnal oxygen saturation, and sleep efficiency remained unchanged in both groups. CONCLUSION: Disabled but clinically stable patients with COPD and hypercapnia do not readily accept and are unlikely to benefit from NNV.

Aged↗
PubMed1996

The importance of patient/ventilator interactions during non-invasive mechanical ventilation.

A number of inferences about diagnostic and therapeutic implications of PVA during non-invasive ventilation may be drawn from these observations. 1. Augmentation of ventilation above spontaneous breathing requires coordination between patient effort and machine output. 2. During sleep, hypocapnia limits the amount that ventilation can be augmented when the ventilator is set in the spontaneous (patient triggered) mode. 3. During wakefulness, it is easy to overventilate a patient because inspiratory drive is much less dependent on CO2 during wakefulness than it is during sleep. 4. The diagnostic and therapeutic implications of PVA and wasted triggering efforts differ depending on the level of inspiratory drive; in the presence of a low drive, PVA is a manifestation of relative hypocapnia and inspiratory unloading; changes in ventilator settings may not be required. In the presence of a high drive, PVA reflects machine sensing failure or abnormal lung mechanics. In this case, sedation or changes in ventilator settings may be required.

Carbon Dioxide↗
PubMed1995

Tidal volume maintenance during weaning with pressure support.

Ventilation was measured in 31 difficult-to-wean patients while pressure support (PS) was reduced by 5 cm H2O every 20 min. Weaning had to be aborted in 14 of 31 patients (Group F) because they met predefined distress criteria. The remaining 17 patients who were able to complete the "weaning test" (Group S) had larger static respiratory compliances (Cstat = 0.08 +/- 0.02 versus 0.05 +/- 0.01 L/cm H2O, p < or = 0.05) and a lower dead space to tidal volume ratio (0.55 +/- 0.05 versus 0.64 +/- 0.06, p < or = 0.05). Group S patients had a larger tidal volume (VT) than did those of Group F at most PS settings. The groups differed with respect to VT maintenance during PS withdrawal (p < 0.01). In Group S, VT fell exponentially with machine support and stabilized at PS levels between 5 and 10 cm H2O. In contrast, Group F patients defended VT at higher PS settings but were unable to maintain VT during distress. Ventilatory response parameters such as the rapid shallow breathing index were of limited value in predicting weaning outcome and yielded receiver operator curve area values between 0.66 and 0.82 over the range of PS settings tested. We conclude that the gradual withdrawal of machine support does not facilitate the recognition of impending respiratory failure.

Aged↗
PubMed1995

Outcome of patients cared for in a ventilator-dependent unit in a general hospital.

We describe our initial experience with the admission of 129 patients for 132 episodes of ventilator-dependence to a self-contained ventilator-dependent unit (VDU) in a general hospital and present a survival comparison between VDU patients and a historic control population from the same institution. Forty-three patients were screened and denied admission to the VDU because long-term ventilator dependence was not felt to be a probable outcome (56%); they were medically unstable, often requiring electrocardiographic monitoring (19%), they had poor rehabilitation potential because of markedly depressed mental status (13%), or they preferred to be treated closer to their homes (12%). Thirteen (9.8%) of the VDU patients died in the hospital compared to 44 (42%) in the historic control group. After exclusion of patients with multiorgan failure (who made up 26% of the control group) and using a proportional hazard model to adjust for group differences in age and disease class, the difference in hospital mortality remained highly significant (p < or = 0.01). Ninety-one of the 119 VDU patients (77%) were ultimately able to return home; 16 (13%) continued to use a ventilator intermittently at night; 26 patients (22%) were permanently placed in nursing homes, all off of the ventilator. Overall, 88% of the 119 patients discharged had been liberated from mechanical ventilation. Ninety-seven (82%) and 86 (72%) remain alive 1 and 2 years after discharge, respectively. Some of the survival benefits may be directly attributed to the VDU. Others reflect a change in treatment philosophy, which was nevertheless reinforced by our VDU experience.

Adult↗
PubMed1994

Acute acid-base disorders associated with status epilepticus.

OBJECTIVE: To analyze the acid-base abnormalities in patients with status epilepticus. DESIGN: We retrospectively reviewed the acid-base disturbances in 38 consecutive patients who had been admitted to the emergency department at a Mayo-affiliated hospital because of status epilepticus between 1982 and 1993. MATERIAL AND METHODS: On the basis of results of arterial blood gas analyses, the acid-base disorders were categorized. In addition, chest roentgenograms and electrocardiograms were reviewed for pulmonary infiltrates and cardiac arrhythmias. RESULTS: Arterial blood gas analysis performed immediately after admission revealed an acid-base abnormality in 32 of 38 patients (84%). Respiratory acidosis was most common (N = 16; 42%) and occurred either alone or in combination with metabolic acidosis. Pulmonary infiltrates were not more common in patients with respiratory acidosis than in other patients. Although cardiac arrhythmias were more common in patients with respiratory or metabolic acidosis (42%) than in those with respiratory alkalosis or normal blood gas values (36%), this difference was not statistically significant. CONCLUSION: We conclude that respiratory acidosis with or without metabolic acidosis is common in patients who have status epilepticus. Respiratory acidosis was not predictive of the final outcome. In our study patients, all acid-base abnormalities resolved spontaneously.

Acid-Base Imbalance↗
PubMed1993

Interrupter mechanics of patients admitted to a chronic ventilator dependency unit.

We analyzed the results of interrupter mechanics tests of 73 consecutive patients who were admitted to a chronic ventilator dependency unit. The purposes of this study were (1) to establish guidelines for grading the severity of airway obstruction based on interrupter mechanics measurements; (2) to estimate the prevalence of airway obstruction in this population; (3) to compare interrupter test results with the clinical assessment of airway function; and (4) to characterize the distribution of bronchodilator-induced changes in isorecoil flow. Measurements from 65 of 73 patients (89%) were considered technically adequate. Of 65 patients, 29 (45%) showed signs of flow limitation during passive expiration. All patients with severe obstruction documented with spirometry during clinical stability were flow-limited and achieved maximal flows < or = 0.45 L/s at recoil pressures of 10 cm H2O. In contrast to measures of expiratory dynamics, the inspiratory resistance of the respiratory system was a poor index of severity of obstruction. In seven of 12 patients, interrupter testing failed to substantiate a clinical diagnosis of severe obstruction while revealing unsuspected obstruction in six of 25 (24%) patients. The administration of 270 micrograms of albuterol increased flows at comparable recoil pressures by > or = 0.1 L/s in 29% of 41 patients. Changes in flow were unimodally distributed and were not correlated with severity of obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗