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Biomedical subjects

J R Rodarte

Publications and source records attributed to J R Rodarte.

At least 37 records · Page 2Linked to original sources

Breathing by double-lung recipients during exercise: response to expiratory threshold loading.

Ventilation during exercise is near-normal in double-lung transplant recipients despite lung denervation. We tested the hypothesis that denervation effects might be unmasked during exercise by exposing these patients to an expiratory load. Eight double-lung recipients and nine intact control subjects were exercised to exhaustion. Ergometer work increased 20 Watt every 2 min; expiratory threshold loading (4 cm H2O) was imposed for five to six breaths at each exercise level; ventilation and O2 consumption were measured. Transplant recipients and control subjects increased ventilation similarly for comparable fractions of maximal work. At maximal exercise, transplant recipients achieved lower work (62 versus 155 W; p < 0.001) and O2 consumption (0.88 versus 2.26 L/min; p < 0.001) than control subjects, with proportional reductions in tidal volume (1.6 versus 2.6 L; p < 0.05) and ventilation (38 versus 79 L/min; p < 0.01). Threshold loading decreased expiratory flow, breathing frequency, and minute ventilation in both groups (p < 0.05). Unlike control subjects, transplant recipients also slowed inspiratory flow (p < 0.05) and prolonged inspiration (p < 0.01), exaggerating the fall in breathing frequency and ventilation (p < 0.01). We conclude that afferent information from pulmonary receptors modulates inspiration during expiratory loading; bilateral denervation disrupts these pathways, causing double-lung recipients to inspire more slowly.

Adult↗

Assessing the reversibility of airway obstruction.

STUDY OBJECTIVE: To determine whether changes of partial expiratory flow-volume curve (PEFV) and inspiratory capacity (IC) detect functional responses to bronchodilator in patients who do not meet the FEV1 criteria for reversibility of airway obstruction. DESIGN/METHODS: The effects of salbutamol (200 microg by metered-dose inhaler) on lung function were examined in 50 patients with asthma and 28 patients with COPD. Measurements evaluated were FEV1, forced expiratory flow at 30% of control FVC from maximal expiratory flow-volume curve (Vm30), forced expiratory flow at 30% of control FVC from PEFV (Vp30), and IC. On a separate occasion, a representative sample of 26 subjects inhaled placebo to determine the 95% confidence limits (CLs) of each of the parameters. RESULTS: A percent and absolute increment of FEV1 above the upper CL was recorded in 28 patients. Of these, 26 had a percent and absolute increase of Vp30, 21 of Vm30, 9 of FVC, and 11 of IC above the 95% CL. Of the 50 patients who did not have an increase in FEV1 above the 95% CL, 25 had a percent and absolute increase in Vp30, 15 of Vm30, 3 of FVC, and 13 of IC above the 95% CL. On average, the percent and absolute increase Vp30 above the 95% CL significantly identified more responders than every other parameter. CONCLUSION: Increases in maximal flow detected by PEFV and/or changes in IC may be substantially obscured by the effects of inspiration to total lung capacity required for the measurement of FEV1 in patients with chronic bronchoconstriction. Decreases in functional residual capacity (FRC) manifested by an increase of IC occur because, in patients whose FRC is dynamically determined, bronchodilatation that increases maximal flow in the tidal breathing range allows patients to breathe at lower lung volumes. Changes of FEV1 frequently fail to detect significant functional response to bronchodilators in patients with chronic airflow obstruction.

Adult↗

Effects of transverse fiber stiffness and central tendon on displacement and shape of a simple diaphragm model.

Our previous experimental results (A. M. Boriek, S. Lui, and J. R. Rodarte. J. Appl. Physiol. 75: 527-533, 1993 and A. M. Boriek, T. A. Wilson, and J. R. Rodarte. J. Appl. Physiol. 76: 223-229, 1994) showed that 1) costal diaphragm shape is similar at functional residual capacity and end inspiration regardless of whether the diaphragm muscle shortens actively (increased tension) or passively (decreased tension); 2) diaphragmatic muscle length changes minimally in the direction transverse to the muscle fibers, suggesting the diaphragm may be inextensible in that direction; and 3) the central tendon is not stretched by physiological stresses. A two-dimensional orthotropic material has two different stiffnesses in orthogonal directions. In the plane tangent to the muscle surface, these directions are along the fibers and transverse to the fibers. We wondered whether orthotropic material properties in the muscular region of the diaphragm and inextensibility of the central tendon might contribute to the constancy of diaphragm shape. Therefore, in the present study, we examined the effects of stiffness transverse to muscle fibers and inextensibility of the central tendon on diaphragmatic displacement and shape. Finite element hemispherical models of the diaphragm were developed by using pressurized isotropic and orthotropic membranes with a wide range of stiffness ratios. We also tested heterogeneous models, in which the muscle sheet was an orthotropic material, having transverse fiber stiffness greater than that along the fibers, with the central tendon being an inextensible isotropic cap. These models revealed that increased transverse stiffness limits the shape change of the diaphragm. Furthermore, an inextensible cap simulating the central tendon dramatically limits the change in shape as well as the membrane displacement in response to pressure. These findings provide a plausible mechanism by which the diaphragm maintains similar shapes despite different physiological loads. This study suggests that changes of diaphragm shape are restricted because the central tendon is essentially inextensible and stiffness in the direction transverse to the muscle fibers is greater than stiffness along the fibers.

Animals↗

Kinematics and mechanics of midcostal diaphragm of dog.

Radiopaque markers were attached to the peritoneal surface of three neighboring muscle bundles in the midcostal diaphragm of four dogs, and the locations of the markers were tracked by biplanar video fluoroscopy during quiet spontaneous breathing and during inspiratory efforts against an occluded airway at three lung volumes from functional residual capacity to total lung capacity in both the prone and supine postures. Length and curvature of the muscle bundles were determined from the data on marker location. Muscle lengths for the inspiratory states, as a fraction of length at functional residual capacity, ranged from 0.89 +/- 0.04 at end inspiration during spontaneous breathing down to 0.68 +/- 0.07 during inspiratory efforts at total lung capacity. The muscle bundles were found to have the shape of circular arcs, with the three bundles forming a section of a right circular cylinder. With increasing lung volume and diaphragm displacement, the circular arcs rotate around the line of insertion on the chest wall, the arcs shorten, but the radius of curvature remains nearly constant. Maximal transdiaphragmatic pressure was calculated from muscle curvature and maximal tension-length data from the literature. The calculated maximal transdiaphragmatic pressure-length curve agrees well with the data of Road et al. (J. Appl. Physiol. 60: 63-67, 1986).

Animals↗

Theory of diaphragm structure and shape.

The muscle bundles of the diaphragm form a curved sheet that extends from the chest wall to the central tendon. Each muscle bundle exerts a force in the direction of its curvature; the magnitude of this force is proportional to the curvature of the bundle. The contribution of this force to transdiaphragmatic pressure is maximal if the direction of bundle curvature is orthogonal to the surface and the curvature is maximal. That is, the contribution of muscle tension to transdiaphragmatic pressure is maximal if the muscle bundles lie along lines that are both geodesics and lines of maximal principal curvature of the surface. A theory of diaphragm shape is developed from the assumption that all muscle bundles have these optimal properties. The class of surfaces that are formed of line elements that are both geodescis and lines of principal curvature is described. This class is restricted. The lines that form the surface must lie in planes, and all lines must have the same shape. In addition, the orientation of the lines is restricted. An example of this class that is similar to the shape of the canine diaphragm is described, and the stress distribution in this example is analyzed.

Animals↗

The relationship between maximal expiratory flow and increases of maximal exercise capacity with exercise training.

We previously reported that patients with mild to moderate airflow limitation have a lower exercise capacity than age-matched controls with normal lung function, but the mechanism of this reduction remains unclear (1). Although the reduced exercise capacity appeared consistent with deconditioning, the patients had altered breathing mechanics during exercise, which raised the possibility that the reduced exercise capacity and the altered breathing mechanics may have been causally related. Reversal of reduced exercise capacity by an adequate exercise training program is generally accepted as evidence of deconditioning as the cause of the reduced exercise capacity. We studied 11 asymptomatic volunteer subjects (58 +/- 8 yr of age [mean +/- SD]) selected to have a range of lung function (FEV1 from 61 to 114% predicted, with a mean of 90 +/- 18% predicted). Only one subject had an FEV1 of less than 70% predicted. Gas exchange and lung mechanics were measured during both steady-state and maximal exercise before and after training for 30 min/d on 3 d/wk for 10 wk, beginning at the steady-state workload previously determined to be the maximum steady-state exercise level that subjects could sustain for 30 min without exceeding 90% of their observed maximal heart rate (HR). The training workload was increased if the subject's HR decreased during the training period. After 10 wk, subjects performed another steady-state exercise test at the initial pretraining level, and another maximal exercise test. HR decreased significantly between the first and second steady-state exercise tests (p < 0.05), and maximal oxygen uptake (VO2max) and ventilation increased significantly (p < 0.05) during the incremental test, indicating a training effect. However, the training effect did not occur in all subjects. Relationships between exercise parameters and lung function were examined by regression against FEV1 expressed as percent predicted. There was a significant positive correlation between VO2max percent predicted and FEV1 percent predicted (p < 0.02), and a negative correlation between FEV1 and end-expiratory lung volume (EELV) at maximal exercise (p < 0.03). There was no significant correlation between FEV1 and maximal HR achieved during exercise; moreover, all subjects achieved a maximal HR in excess of 80% predicted, suggesting a cardiovascular limitation to exercise. These data do not support the hypothesis that the lower initial VO2max in the subjects with a reduced FEV1 was due to deconditioning. Although increased EELV at maximal exercise, reduced VO2max and a reduced VO2max response with training are all statistically associated with a reduced FEV1, there is no direct evidence of causality.

Case-Control Studies↗

Tolerance of volunteers to cyclosporine A-dilauroylphosphatidylcholine liposome aerosol.

Cyclosporine A (CsA) in liposomes of dilauroylphosphatidylcholine (DLPC), containing 118 micrograms of CsA/L of aerosol with a particle size of 1.6 to 1.7 micron diameter, was inhaled by 10 nonsmoking, normal volunteers each for 45 min. Aerosol was administered through an Aerotech II nebulizer (CIS-US, Inc., Bedford, MA) mouthpiece. Eight of the 10 volunteers had tracheal irritation and intermittent coughing following exposure. FEV1 and FVC values were mildly reduced, but returned to normal in 1 h. Blood chemical and hematologic values were unchanged at any time point after as opposed to before inhalation. Nine of the 10 volunteers later inhaled DLPC only, administered through the nebulizer mouthpiece. There was no change in FEV1 or FVC values, and there was no coughing or tracheal irritation. Subsequently, five of the volunteers who had previously had respiratory reactions inhaled CsA-DLPC liposome aerosol for 45-min, but through a mouth-only face mask. There was no tracheal irritation, coughing, or changes in spirometric measures. Blood concentrations of CsA at 15 min after the 45-min inhalation with a face mask averaged 83 +/- 42 ng/ml (mean +/- SD). At 24 h after treatment, CsA was undetectable in blood of the initial 10 volunteers. These studies indicate that CsA-DLPC liposome aerosol can be safely explored as a treatment for patients with moderately severe asthma.

Administration, Inhalation↗

Vital capacities in acute and chronic airway obstruction: dependence on flow and volume histories.

The aim of this study was to investigate whether measurements of vital capacity (VC) are affected by the direction of the manoeuvre (inspiratory vs expiratory) and by the rate of expiratory flow. The study was performed on 25 individuals with chronic airway obstruction (CAO) and a forced expiratory volume in one second (FEV1) (expressed in standardized residuals (SR)) of -2.0+/-1.4 SD (CAO group), and 10 asthmatic subjects with methacholine (MCh)-induced bronchoconstriction (FEV1 -23+/-1.02 SR) (MCh group). VCs were measured during fast inspiration following both slow (FIVCse) and forced (FIVCfe) expiration from end-tidal inspiration to residual volume (RV), and during slow (EVC) or forced (FVC) expiration from total lung capacity (TLC). In the CAO group, FVC was the smallest volume (3.75+/-1.03 L) and significantly different from the other three estimates of VC; FIVCse (4.03+/-0.91 L) was the largest volume and significantly different from FVC and FIVCfe (3.83+/-0.98 L). In the MCh group, FVC (4.16+/-0.94 L) and EVC (4.19+/-0.89 L) were the largest volumes, although only the difference between FVC and FIVCfe (3.76+/-0.81 L) reached statistical significance. These data suggest that both flow and volume histories contribute to decreased vital capacities during bronchoconstriction. However, whereas increasing expiratory flow always tends to decrease vital capacity, the volume history of full inflation has different effects in chronic and acute bronchoconstriction, probably due to different effects on airway calibre. These results stress the importance of using standardized manoeuvres in order to obtain comparable values of vital capacity.

Acute Disease↗

Lung mechanics during induced bronchoconstriction.

To elucidate differences in lung mechanics, we investigated the relative changes of partial forced expiratory flows at 50 and 30% of vital capacity, pulmonary resistance (RL), dynamic elastance (Edyn), and the effects of a deep inhalation (DI) on maximal flows, Edyn, and RL in eight asthmatic and eight normal individuals during bronchial challenges with methacholine, histamine, and ATP. RL was partitioned into inspiratory and expiratory resistance. Different constrictor agents did not induce specific patterns of response. For a given decrement of flow at 50 and 30% vital capacity, RL increased significantly more in normal than in asthmatic individuals. The ratio of inspiratory to expiratory RL was always < 1 at baseline but became > 1 in the majority of asthmatic and normal individuals when RL exceeded 12.2 +/- 0.9 cmH2O.1-1.s, suggesting that tidal inspiration may have induced transient bronchodilation in more constricted subjects. In asthmatic individuals, DI had a significantly smaller effect on flow but not on RL compared with normal individuals. The recovery of RL and Edyn after DI was faster than Edyn for both normal and asthmatic individuals. These findings are consistent with the idea that asthmatic individuals have a stronger peripheral response to agonists than normal individuals.

Adenosine Triphosphate↗

Zone of apposition in the passive diaphragm of the dog.

We determined the regional area of the diaphragmatic zone of apposition (ZAP) as well as the regional craniocaudal extent of the ZAP (ZAPht) of the passive diaphragm in six paralyzed anesthetized beagle dogs (8-12 kg) at residual lung volume (RV), functional residual capacity (FRC), FRC + 0.25 and FRC + 0.5 inspiratory capacity, and total lung capacity (TLC) in prone and supine postures. To identify the caudal boundary of the ZAP, 17 lead markers (1 mm) were sutured to the abdominal side of the costal and crural diaphragms around the diaphragm insertion on the chest wall. Two weeks later, the dogs' caudal thoraces were scanned by the use of the dynamic spatial reconstructor (DSR), a prototype fast volumetric X-ray computer tomographic scanner, developed at the Mayo Clinic. The three-dimensional spatial coordinates of the markers were identified (+/- 1.4 mm), and the cranial boundary of the ZAP was determined from 30-40 1.4-mm-thick sagittal and coronal slices in each DSR image. We interpolated the DSR data to find the position of the cranial and caudal boundaries of the ZAP every 5 degrees around the thorax and computed the distribution of regional variation of area of the ZAP and ZAPht as well as the total area of ZAP. The ZAPht and area of ZAP increased as lung volume decreased and were largest near the lateral extremes of the rib cage. We measured the surface area of the rib cage cephaled to the ZAP (AL) in both postures in another six beagle dogs (12-16 kg) of similar stature, scanned previously in the DSR. We estimated the entire rib cage surface area (Arc = AZAP + AL). The AZAP as a percentage of Arc increased more than threefold as lung volume decreased from TLC to RV, from approximately 9 to 29% of Arc.

Anesthesia, General↗

Displacements and strains in the costal diaphragm of the dog.

Radiopaque markers were attached at 1- to 2-cm intervals along three nearby muscle bundles to cover rectangular regions of the mid-costal diaphragms of seven dogs. The markers were tracked by biplane video fluoroscopy during spontaneous breathing (SB), mechanical ventilation with the same tidal volume (MV), and at inflation to total lung capacity (TLC) in the prone and supine positions. The three-dimensional positions of the markers at functional residual capacity (FRC), at end inspiration during SB and MV, and at TLC were determined, and the strains in the plane of the diaphragm relative to FRC were calculated. The principal strains were found to lie nearly along the muscle bundle direction and perpendicular to it. The principal strains along the muscle bundles, which describe muscle shortening, were uniform among the three bundles and uniform along the bundle for MV. For SB, in the prone and supine positions, shortening was approximately 30% greater in the middle of the bundle than near the central tendon and chest wall. Although the tidal volumes were the same for SB and MV, the shortening was larger for SB. The strains perpendicular to the bundle direction were not significantly different from zero. It appears that, for the loads that occur during tidal breathing, the diaphragm is inextensible in the direction perpendicular to the muscle direction. There is a very small displacement of the costal diaphragm at its insertion on the chest wall. The displacement at the central tendon is primarily a result of muscle shortening and rotation of the arc of the muscle around its insertion on the chest wall.

Animals↗

Finite-element analysis of stress in the canine diaphragm.

Stress in the diaphragm, transdiaphragmatic pressure, and diaphragm shape are interrelated by a balance of forces. Using precise in vivo measurements of diaphragm shape and transdiaphragmatic pressure distribution in combination with finite-element analysis (ANSYS), we determined the direction and magnitude of stress in the passive diaphragm at relaxation volume. Lead spheres sutured along muscle bundles identified muscle bundle location and orientation in vivo. The x, y, and z coordinates of the lead spheres and entire surface of the diaphragm, excluding the zone of apposition, were determined to within 1.4 mm. Thin shell elements were used to construct a finite-element model of the diaphragm with a 2.1- to 4.2-mm internodal spacing. The diaphragm was assumed to have a uniform thickness of 2.5 mm, and magnitude and direction of the principal stresses were computed. The results show that 1) diaphragm stress is nonuniform and anisotropic (i.e., varies both with location on diaphragm surface and direction examined), 2) largest stress (sigma 1) is aligned with muscle bundles and is two to four times larger than sigma 2 (perpendicular to sigma 1 in diaphragm plane), and 3) stress along the muscle bundles is larger in vivo under conditions of biaxial stress than at same length in vitro under uniaxial stress. Although diaphragm stress and tension have often been assumed to be uniform, our finding that stress is oriented primarily along the muscle fibers should be considered in future models of the diaphragm.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Inferences on passive diaphragm mechanics from gross anatomy.

The diaphragm is a relatively thin curved structure that is categorized in mechanics as a membrane. Tension in the membrane is given by the product of muscle thickness and stress parallel to the fiber bundles. If all muscle fibers were cylindrical and extended from origin to insertion, the ratio of thickness near the chest wall (CW) to thickness near the central tendon (CT) would vary inversely with the ratio of CW to CT perimeters. In freshly excised diaphragms of 36 mongrel dogs, the ratios of the perimeters (CT/CW) in the right and left costal diaphragm were 0.63 +/- 0.04 and 0.62 +/- 0.04, respectively. The means of the ratio of thickness near CW to that near CT in the right and left costal regions were 0.96 +/- 0.07 and 0.95 +/- 0.05, respectively, consistent with a nearly constant relationship between costal diaphragm membrane tension and muscle stress in the direction of the fibers. In the crural diaphragm, the average ratio of the perimeters of the insertions on CT to CW was 1.16 +/- 0.10. The average ratio of thickness of crural CW to CT was 1.25 +/- 0.11. The discrepancy between the perimeter ratio and thickness ratio in the costal diaphragm is incompatible with the muscle consisting of uniform fibers extending from CW to CT. Our data suggest that muscle fibers are either in series with a smaller number along the smaller perimeter or that they terminate by tapering within the muscle bundle. Both arrangements are consistent with previous anatomic studies (Gordon et al. J. Morphol. 201: 131-143, 1989). Having a nonuniform number of fibers mechanically in series is compatible with uniform stress in the fibers if the membrane is sufficiently curved as in a domed structure.

Animals↗

Estimation of ventilatory capacity during submaximal exercise.

There is presently no precise way to determine ventilatory capacity for a given individual during exercise; however, this information would be helpful in evaluating ventilatory reserve during exercise. Using schematic representations of maximal expiratory flow-volume curves and individual maximal expiratory flow-volume curves from four subjects, we describe a technique for estimating ventilatory capacity. In these subjects, we measured maximal expiratory flow-volume loops at rest and tidal flow-volume loops and inspiratory capacity (IC) during submaximal cycle ergometry. We also compared minute ventilation (VE) during submaximal exercise with calculated ventilatory maxima (VEmaxCal) and with maximal voluntary ventilation (MVV) to estimate ventilatory reserve. Using the schematic flow-volume curves, we demonstrated the theoretical effect of maximal expiratory flow and lung volume on ventilatory capacity and breathing pattern. In the subjects, we observed that the estimation of ventilatory reserve with use of VE/VEmaxCal was most helpful in indicating when subjects were approaching maximal expiratory flow over a large portion of tidal volume, especially at submaximal exercise levels where VE/VEmaxCal and VE/MVV differed the most. These data suggest that this technique may be useful in estimating ventilatory capacity, which could then be used to evaluate ventilatory reserve during exercise.

Adult↗