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K S Deoras

Publications and source records attributed to K S Deoras.

10 recordsLinked to original sources

Comparison of gas and liquid ventilation: clinical, physiological, and histological correlates.

To differentiate the effects of gas and liquid ventilation on cardiopulmonary function during early development, we compared the clinical, physiological, and histological profiles of gas- and liquid-ventilated preterm lambs (n = 16; 108-116 days gestation). Immediately after cesarean section delivery, ventilation commenced using gas delivered by a volume ventilator (n = 9) or liquid perfluorochemical (n = 7) delivered by a mechanically assisted liquid ventilation system. Pulmonary gas exchange, acid-base status, vital signs, and respiratory compliance were assessed during the 3-h protocol; sections of the lungs were obtained for histological analyses when the animals were killed. Six of nine gas-ventilated lambs expired from respiratory failure before 3 h, with the remaining animals experiencing severe respiratory insufficiency, pneumothoraces, and cardiovascular deterioration. Six of seven liquid-ventilated lambs survived with good gas exchange and cardiovascular stability and without fluorothorax; one experienced ventricular fibrillation before 1 h and expired despite pulmonary stability. Respiratory compliance was significantly greater in the liquid- than in the gas-ventilated lambs. Histological analyses of gas-ventilated lungs demonstrated nonhomogeneous lung expansion, with thick-walled gas exchange spaces containing proteinaceous exudate, hemorrhage, and hyaline membranes. In contrast, liquid-ventilated lungs appeared clear, with thin-walled and uniformly expanded gas exchange spaces that were free of hyaline membranes and luminal debris. Morphometric analyses demonstrated that surface area and gas exchange index were greater in the liquid- than in the gas-ventilated lambs. These results indicate that elimination of surface active forces by liquid ventilation during early development provides more effective gas exchange with less barotrauma compared with gas ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effect of position on the mechanical interaction between the rib cage and abdomen in preterm infants.

To determine the influence of body position on chest wall and pulmonary function, we studied the ventilatory, pulmonary mechanics, and thoracoabdominal motion profiles in 20 preterm infants recovering from respiratory disease who were positioned in both the supine and prone position. Thoracoabdominal motion was assessed from measurements of relative rib cage and abdominal movement and the calculated phase angle (an index of thoracoabdominal synchrony) of the rib and abdomen Lissajous figures. The ventilatory and pulmonary function profiles were assessed from simultaneous measurements of transpulmonary pressure, airflow, and tidal volume. The infants were studied in quiet sleep, and the order of positioning was randomized across patients. The results demonstrated no significant difference in ventilatory and pulmonary function measurements as a function of position. In contrast, there was a significant reduction (-49%) in the phase angle of the Lissajous figures and an increase (+66%) in rib cage motion in prone compared with the supine position. In addition, the degree of improvement in phase angle in the prone position was correlated to the severity of asynchrony in the supine position. We speculate that the improvement in thoracoabdominal synchrony in the prone position is related to alterations of chest wall mechanics and respiratory muscle tone mediated by a posturally related shift in the area of apposition of the diaphragm to the anterior inner rib cage wall and increase in passive tension of the muscles of the rib cage. This study suggests that the mechanical advantage associated with prone positioning may confer a useful alternative breathing pattern to the preterm infant in whom elevated respiratory work loads and respiratory musculoskeletal immaturity may predispose to respiratory failure.

Abdominal Muscles

Maturational changes in airway smooth muscle structure-function relationships.

Airways become less compliant with age. When examined at either extreme of the developmental spectrum, airway smooth muscle (ASM) undergoes changes that parallel the trachea: both passive and active stress increase from preterm to adult. To determine how ASM changes throughout maturation, trachealis muscles from sheep airways of five age groups (group 1, less than 110 d gestation; group 2, 110-124 d gestation; group 3, 125-140 d gestation; group 4, newborn; and group 5, adult) were separated from their cartilaginous supports and cleaned of their mucosa and serosa. The length at which active stress was optimal was determined and passive and active stress were measured. Concentration-effect curves for acetylcholine (ACh) and KCl were performed at the length at which active stress was optimal. Morphometric analysis of the muscle was performed by computerized image analysis. At the length at which active stress was optimal, both passive and active stress increased with maturation (p less than 0.001). Concentration-effect curves for both ACh and KCl also showed a significant increase in active stress as a function of dose and of age (p less than 0.002), and the ED50 for ACh decreased with maturation (p less than 0.005). Although muscle length, thickness, and area increased with age (p less than 0.005), the ratio of contractile to connective tissue within the muscle bundle remained constant throughout maturation. These data demonstrate that ASM undergoes a progressive increase in contractility and sensitivity to ACh throughout maturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine

Structure-function of airway generations 0 to 4 in the preterm lamb.

Five generations of airways from 15 preterm lambs of 130-137 d (90% term) gestation were studied to investigate the effect of generation on structure-function of preterm airways. Airway rings were measured to determine the internal radius (r), and wall thickness (t). The ratio r/t was then calculated as a morphometric index used in the determination of wall stress. Airway rings from each generation were placed in tissue baths to compare passive, active, and total force development. Contraction via membrane depolarization (KCl) and muscarinic receptor stimulation (acetylcholine) were evaluated. As r and t decreased, r/t declined by a factor of 3.48 down the generations. At the optimal length for active force development, the passive, active, and total stresses decreased significantly as a function of generation. The receptor-mediated response to acetylcholine was significantly less in generations 0, 1, and 2 than in generations 3 and 4. No differences were found among the various generations in contractility as measured by the response to KCl. These data suggest that based on the interrelationship between airway morphometry and force development the trachea is exposed to greater wall stress than the lower airways during continuous positive airway pressure. Taken together, these data may help to explain the structural changes, such as tracheomegaly, as well as the physiologic changes in airway reactivity seen in the premature infant after mechanical ventilation.

Acetylcholine

Effects of inspiratory resistive loading on chest wall motion and ventilation: differences between preterm and full-term infants.

The ability to maintain effective tidal volume and minute ventilation during resistive loaded breathing depends on both adequate central neural respiratory output response and respiratory system mechanical properties such as respiratory muscle strength and chest wall stability. We hypothesized that chest wall instability limits the ability of the preterm (PT) infant to respond to inspiratory resistive loading (IRL) compared with full-term (FT) infants. To test this hypothesis, we subjected eight FT and 10 PT infants to IRL with loads of 1.3, 2, and 6 times intrinsic lung resistance and measured steady state tidal volume (VT), minute ventilation (VE), and chest wall motion. Thoracoabdominal asynchrony was measured by respiratory inductive plethysmography and quantitated by measuring the phase angle, theta, between rib cage and abdominal motion (0 degrees = synchronous motion, 180 degrees = paradoxic motion). At baseline, VT/kg (mL/kg, mean +/- SEM) was similar between PT (7.0 +/- 0.7) and FT (7.5 +/- 0.5) infants. VE/kg (mL/min/kg) was greater in PT (545 +/- 50) than in FT (385 +/- 33) infants (p < 0.05) as a result of increased respiratory frequency in the former. PT infants demonstrated significantly greater chest wall asynchrony (theta = 38 +/- 9 degrees) than FT infants (theta = 9 +/- 3 degrees) (p < 0.01). With the highest resistive loads, VT decreased significantly in the PT but not the FT infants. Furthermore, during IRL, VE decreased to 417 +/- 50 mL/min/kg (p < 0.05) and theta increased to 56 +/- 7 (p < 0.05) in the PT infants, whereas no significant change in either value was observed in the FT group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological

Interaction between chest wall motion and lung mechanics in normal infants and infants with bronchopulmonary dysplasia.

Asynchronous or paradoxic motion between the rib cage and abdomen may be seen in infants with lung disease. We have recently shown that after bronchodilator administration, the degree of asynchrony decreases proportionately to the improvement in lung mechanics. However, whether such thoraco-abdominal asynchrony (TAA) is a useful indicator of lung function in a cross-sectional population, i.e., whether asynchrony correlates with baseline lung mechanics, is unknown. Therefore, we quantitated the degree of TAA using respiratory inductive plethysmography during quiet sleep in ten infants with bronchopulmonary dysplasia (BPD) and six weight-matched control infants. We displayed abdominal wall (AB) and rib cage (RC) motion on an X-Y recorder, and from the tidal breathing loop we calculated a phase angle phi, between 0 degrees and 180 degrees as an index of asynchrony (synchronous RC/AB motion = 0 degrees, paradox = 180 degrees). Lung resistance (RL) and compliance/kg (CL/kg) were calculated from esophageal and mouth pressure, tidal volume, and tidal flow. As expected, BPD infants had abnormally high RL, and low CL/kg when compared to controls. All infants with BPD displayed marked thoraco-abdominal asynchrony (phi = 102 +/- 16 degrees, mean +/- SEM; range 35 degrees-160 degrees) with controls displayed synchronous chest wall motion (phi = 8 +/- 3 degrees, range 0 degrees-15 degrees) (P less than 0.001). The degree of TAA was significantly correlated with RL (r = 0.773, P less than 0.001) and inversely correlated with CL/kg (r = -0.67, P less than 0.01). We conclude that in infants of similar weight, TAA may be used as a cross-sectional index reflecting both resistive and elastic properties of the lungs.

Abdominal Muscles

Developmental changes in tracheal structure.

Mechanical properties of the proximal airways are known to change with development; the highly compliant airways of the immature animal become stiffer and less collapsible with increasing age. Although the relationship between tracheobronchial architecture and function has been described for adult physiology, little is known regarding this relationship during early development. This study was, therefore, designed to test the hypothesis that alterations in tracheal morphometry parallel developmental differences in tracheal functional properties. Tracheal segments obtained from 29 lambs ranging in age from 70% of gestation to full-term newborn lambs up to 6 d old were examined using anatomic, morphometric, and histochemical techniques. The results showed 1) progressive increases in the dimensions of the trachea and the tracheal wall components, 2) alterations in the geometric arrangement of the tracheal ring, and 3) changes in the compositional characteristics of the tracheal cartilage with maturation. These findings demonstrate alterations in tracheal architecture, each of which contribute to the greater stiffness of the trachea, in older animals. When considered together, these factors help explain the differences in tracheal functional characteristics with development.

Aging

Structural deformation of the preterm trachea during acute distention and collapse.

The compliant airways of the premature neonate undergo episodic distention and collapse in response to changes in transmural pressure such as occur during spontaneous breathing, mechanical ventilation, and various therapeutic maneuvers. To identify and quantitate the effects of distending and collapsing transmural pressures on the structure of immature airways, tracheal segments from fetal rabbits, fixed at 0, +30, and -30 cm H2O transmural pressure, were examined using histologic and morphometric techniques. In comparison to control sections fixed at 0 cm H2O transmural pressure, application of distending pressures led to evagination of the posterior tracheal wall and significantly increased (P less than 0.05) cross-sectional area, antero-posterior diameter, circumference and muscle length, and decreased muscle thickness. Collapsed tracheal segments (-30 cm H2O) demonstrated invagination of the posterior wall and significantly (P less than 0.05) lower cross-sectional area, and antero-posterior diameter compared to the control segments; all the other parameters remained relatively unchanged. These data demonstrate extreme changes in tracheal geometry in response to the acute application of transmural pressure. From a methodological perspective, these observations suggest that fixation pressures may present significant artifact in histological analyses. Functionally, the noted deformation may lead to alterations in anatomic dead space and airway resistance, and mechanical function of the airways; all of which may compromise respiratory status in ventilated premature infant.

Airway Resistance

Use of a touch sensitive screen and computer assisted image analysis for quantitation of developmental changes in pulmonary structure.

The extensive changes in pulmonary function occurring during early development may reflect variations in the anatomic structure of the respiratory apparatus during this period. Accurate definition of these alterations could yield important information concerning the structure-function correlations of the respiratory system. To facilitate the acquisition of morphometric data from histologic sections of pulmonary tissues, we propose the use of a computer assisted image analysis system with a touch sensitive screen as an interactive peripheral. This allows planimetric measurements and computation of the dimensions of areas of selected light intensities within an image. We present the description, design, and applications of such an image analysis system and report representative results regarding developmental changes in pulmonary structure. In addition, we correlate these results with previously published information regarding pulmonary mechanics during early development to help clarify the maturational changes in pulmonary structure-function relationships.

Animals

Structural changes in the tracheae of preterm lambs induced by ventilation.

Compliant immature airways sustain significant deformation following positive pressure ventilation. To evaluate the structural changes induced by in vivo positive pressure ventilation, tracheae of preterm lambs (107-116 d gestational age) were studied histologically. Nonventilated (group I: n = 7) and ventilated (group II: n = 7) tracheal segments were excised and studied by histologic and morphometric techniques. Computerized image analysis was used to measure dimensions of tracheal wall components and of the tracheal section. The circumference, diameter, and cross-sectional area of the section as well as the length of the trachealis muscle were significantly greater; although the thickness of the muscle and cartilage were seen to be significantly lower in group II sections compared to group I sections. Also, in comparison to group I, in group II sections there was lesser overlap of the posterior free ends of tracheal cartilage and the epithelial layer was flattened and focally abraded. Our findings demonstrate structural changes in the airway of preterm animals and characterize alterations in the geometric arrangement of muscle and cartilage after PPV. These results suggest possible structural mechanisms for the functional changes seen during and subsequent to mechanical ventilation.

Animals