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Biomedical subjects

T H Shaffer

Publications and source records attributed to T H Shaffer.

At least 19 recordsLinked to original sources
PubMed1992

Caffeine potentiates airway responsiveness in the neonatal lamb.

In contrast to its effect on airway smooth muscle in the adult, in vitro studies have shown that caffeine significantly increases active tension in airway smooth muscle in the neonatal lamb. To determine if caffeine has a physiological effect on airway function during early development, we studied the effect of caffeine on acetylcholine-induced bronchoconstriction in two groups of neonatal lambs. The animals were anesthetized, paralyzed, and maintained normoxic and normocapnic with mechanical ventilation. Pulmonary mechanics were evaluated as indices of airway tone, and functional residual capacity was used as an index of lung volume; heart rate and mean arterial pressure were used to assess cardiovascular status. Acetylcholine-induced bronchoconstriction was evaluated as percentage changes of airway conductance and lung compliance from baseline, before and 1 hour after administration of normal saline or caffeine, and it was further analyzed with respect to the dose that produced a 20% change in those values (PD20). There were no significant alterations in baseline lung mechanics, lung volume, or mean arterial pressure following saline or caffeine infusion. However, caffeine produced a left shift in the acetylcholine dose-response curve for conductance and compliance and a significant decrease (-52%; P less than 0.001) in PD20 for conductance. There were no significant alterations in any parameter following saline administration. Since caffeine is used commonly for the treatment of apnea of prematurity, it is noteworthy that caffeine increases airway reactivity at clinically relevant doses. These findings raise important issues regarding the use of caffeine for the treatment of apnea of prematurity.

Acetylcholine↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

Increased respiratory drive and limited adaptation to loaded breathing in bronchopulmonary dysplasia.

Ventilatory parameters and respiratory drive with and without an added acute resistive load were assessed in 11 healthy preterm infants and 11 infants with bronchopulmonary dysplasia (BPD). Lung mechanics (breathing frequency, tidal volume, minute ventilation, compliance, and resistance) were determined with esophageal manometry and pneumotachography. Respiratory drive was assessed by determining the airway pressure measured 100 ms after the onset of an inspiratory effort against an occlusion. Infants were studied at baseline and with an external inspiratory resistive load of 213.7 cm H2O/L/s. Infants with BPD had similar breathing frequency, tidal volume, and minute ventilation, lower compliance, and greater resistance and airway pressure at 100 ms than healthy preterm infants at rest. With loading, healthy preterm infants demonstrated increased airway pressure at 100 ms, whereas infants with BPD showed no change. Although the healthy preterm infants had decreased minute ventilation and tidal volume with loading, decreases in ventilation were greater in the infants with BPD. These data demonstrate that infants with BPD have responded to a chronic intrinsic load with increased drive. However, this may result in decreased ventilatory reserve and hence, a limited ability to adapt to acute pulmonary loads.

Airway Resistance↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

Effect of nasal CPAP on thoracoabdominal motion in neonates with respiratory insufficiency.

Thoracoabdominal motion (TAM) profiles were determined in ten infants requiring nasal continuous positive airway pressure (CPAP) and supplemental oxygen, in order to assess the influence of CPAP on chest wall function in infants with respiratory insufficiency. (TAM) was quantitated by respiratory inductive plethysmography, measuring relative motion of the rib cage and abdomen. Baseline pulmonary function (without CPAP support) was assessed from simultaneous measurements of transpulmonary pressure, air flow, and tidal volume. Measurements of (TAM) were acquired at baseline and at nasal CPAP levels of 0, 3, 5, and 8 cm H2O, in randomized order. Without CPAP, relative paradoxical motion occurred, i.e., the rib cage collapsed inward instead of expanding outward early in inspiration. With CPAP, TAM resembled the pattern in preterm infants, without lung disease. We found that nasal CPAP lowers the phase angle in infants with respiratory insufficiency (P less than 0.003), indicating improved synchrony of TAM. In addition, the improvement with nasal CPAP was related to the severity of pulmonary compromise at baseline. We speculate that changes in TAM associated with nasal CPAP arise from an interaction between pulmonary mechanics and an enhanced stability of the chest wall. In this context, the greater synchrony of TAM is suggestive of an improved breathing strategy. This may be a noninvasively obtainable marker of an effective nasal CPAP level in infants with altered pulmonary and chest wall mechanics.

Humans↗
PubMed1991

Immediate improvement in lung volume after exogenous surfactant: alveolar recruitment versus increased distention.

To determine whether changes in lung volume may be responsible for the clinical improvement in preterm infants given exogenous surfactant, we measured functional residual capacity (FRC), lung mechanics, and partial pressure of oxygen in seven ventilated neonates (birth weight 1080 +/- 361 gm (mean +/- SD); gestational age 28.3 +/- 2.6 weeks) less than 9 hours of age who had findings typical of hyaline membrane disease. All patients received 100 mg/kg calf lung surfactant extract. FRC was measured by a closed-circuit helium-dilution technique, and lung mechanics were determined by least mean squares analysis. FRC increased in all patients (range 56% to 330%; p less than 0.03). Dynamic lung compliance and total airway conductance did not change. Mean +/- SEM specific lung compliance (dynamic lung compliance/FRC) decreased 55.93% +/- 4.27% (p less than 0.02) and mean specific conductance (total airway conductance/FRC) decreased 45.91% +/- 9.74% (p less than 0.009). Mean alveolar/arterial partial pressure of oxygen ratio decreased 51.0% +/- 8.67% (p less than 0.01). These data indicate that the immediate improvement in oxygenation after surfactant administration is related to increased lung volumes. The decrease in specific lung compliance and specific airway conductance is suggestive of increased distention rather than recruitment of functional alveoli.

Functional Residual Capacity↗
PubMed1991

Dissociation between the effects of theophylline and caffeine on premature airway smooth muscles.

Xanthine derivatives relax adult airway smooth muscle (ASM). To determine whether caffeine and theophylline relax preterm ASM contracted by acetylcholine, 27 tracheal rings obtained from seven preterm lambs (120-135 d gestation) were studied. ASM was contracted using 10(-5) M acetylcholine (control) after the muscle was stretched to the length at which maximum active tension was developed isometrically. Concentration-effect curves for each xanthine were obtained by cumulative addition of the drug. Theophylline produced a significant decrease (p less than 0.001) in active tension at each dose, whereas caffeine significantly increased (p less than 0.001) active tension at 10(-4) and 10(-3) M concentrations. Addition of caffeine and theophylline to previously uncontracted ASM did not alter tension. Thus, it appears that, in contrast to their effect on adult ASM, the xanthine derivatives caffeine and theophylline have differential effects on prestimulated ASM in preterm lambs. These findings raise important questions about various aspects of the current therapeutic use of caffeine and theophylline.

Acetylcholine↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

Differential effects of pancuronium bromide on cardiopulmonary function in the neonatal lamb.

The effect of pancuronium bromide (Panc Br) on resting cardiopulmonary function and cardiopulmonary responses to intravenous injection of acetylcholine (Ach) and histamine (H) was evaluated in neonatal lambs. The animals were mechanically ventilated and managed to maintain physiologic gas exchange and acid-base conditions. A proximal segment of the cervical trachea was bypassed; the developed pressure response of this segment (P cervical trach) was used as a direct indication of airway smooth muscle contraction and bronchoconstriction. Pulmonary resistance (Rp) and functional residual capacity were determined. The change in Rp from resting values was used as a functional indicator of central and peripheral airway bronchoconstriction. Cardiovascular function and responses were evaluated from changes in mean arterial pressure and heart rate. Following Panc Br, there was a significant reduction in Ach-induced P cervical trach (-50 +/- 9.2% SE) and Rp (-46 +/- 2.4% SE). In contrast, Panc Br did not significantly change Ach-induced bradycardia and hypotension, cardiopulmonary responses to H, and resting cardiopulmonary function. The differential effects of Panc Br on cardiopulmonary function appear to be related to regional differences between cardiovascular and airway smooth muscle muscarinic receptors in the neonate. The results of this study elucidate a mechanism which may explain previously reported variability in the effect of Panc Br on neonatal cardiopulmonary function. Furthermore, the Panc Br-related attenuation of airway smooth muscle responses suggests that this form of neuromuscular blockade affects the regulation of airway tone and may influence the susceptibility of the neonate to airway deformation consequent to mechanical ventilation.

Acetylcholine↗
PubMed1990

Neonatal gastric intubation: differential respiratory effects between nasogastric and orogastric tubes.

The acute effects of nasogastric (NG) and orogastric (OG) tube placement on pulmonary function of neonates was assessed as a function of infant weight. Lung function was obtained on 14 healthy infants weighing less than 2 kg and 10 infants heavier than 2 kg with an NG and an OG tube in place. Additionally, 15 infants were studied for a third time without gastric intubation. Lung function was determined with an esophageal balloon and by pneumotachography (PeDS) via the least mean square analysis technique. Neither the below-2 kg infants nor the above-2 kg infants had apparent clinical compromise with NG and OG tube placement. Infants weighing less than 2 kg, however, demonstrated diminished minute ventilation and respiratory rate and had increased pulmonary resistance, resistive work of breathing, and peak transpulmonary pressure change with NG tube, as compared to OG tube, placement. The above-2 kg infants demonstrated no change in pulmonary function with NG vs. OG tube placement. These data indicate that small neonates demonstrate significant pulmonary compromise with NG placement that may not be clinically apparent.

Airway Resistance↗
PubMed1990

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↗