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Biomedical subjects

T H Shaffer

Publications and source records attributed to T H Shaffer.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1990

Emergence of the brain-stem auditory evoked potential in the premature lamb.

Brain-stem auditory evoked potentials (BAEPs) were elicited by bone conducted stimuli in the very immature lamb following delivery, wherein liquid ventilation techniques were utilized to control cardiopulmonary and acid-base conditions, independent of umbilical-placenta support. Unlike previous studies of the in utero fetal lamb in which the BAEP could not be elicited by earphone delivered stimuli until 117 days gestation, our results demonstrate that the BAEP emerges at least as early as 106 days gestation in the lamb and consists of a full complement of readily discernible and reproducible wave forms. In addition, the results demonstrate substantial maturation of the BAEP from 106 to 122 days gestation during which time there is a significant decrease in absolute and interpeak latencies with an increase in developmental age. It is concluded that the ability to elicit the BAEP utilizing bone conduction at this early stage of gestation is related to improved stimuli delivery. Furthermore, this study demonstrates the feasibility and flexibility afforded by liquid ventilation and bone conduction BAEP techniques to study brain-stem function at particularly vulnerable stages of development.

Animals↗
PubMed1990

Liquid ventilation of human preterm neonates.

This report details the application of liquid perfluorochemical ventilation for investigational therapy in three human preterm neonates (gestational ages 28, 24, and 23 weeks) in whom conventional therapies for severe respiratory distress had failed. Liquid ventilation was performed without difficulty in each infant for two 3- to 5-minute cycles by means of gravity-assisted technique. Marked improvement in lung distensibility, without a change in cardiovascular status, occurred in all three infants after liquid ventilation; oxygenation improved in two. All infants died within 19 hours of liquid ventilation, and there was no evidence of retained perfluorochemical fluid in the lungs or pleural space. Death was probably related to the severity of lung disease before the initiation of liquid ventilation. This satisfactory initial outcome shows the feasibility and potential of this treatment of pulmonary dysfunction in the preterm neonate.

Airway Resistance↗
PubMed1990

Thoracoabdominal asynchrony in infants with airflow obstruction.

Thoracoabdominal asynchrony (TAA) has long been thought clinically useful in the assessment of airflow obstruction (AO) in infants. To test the hypothesis that the measurement of TAA is useful in the assessment of lung mechanics in infants with AO, we have used respiratory inductive plethysmography (RIP) to quantity TAA. We compared changes in TAA to changes in lung mechanics before and after aerosolized bronchodilator (BD) administration in 13 infants. Abdominal wall (AB) and rib cage (RC) motion were displayed on an X-Y recorder in a Lissajous figure. Asynchrony between RC and AB motion was quantified by comparing the width m of the Lissajous figure (difference between AB inspiratory and expiratory positions) at mid-RC excursion with the total AB excursion at its extremes (s). Phase angle phi ws computed as sin phi = m/s (or phi = 180 degrees - mu, where sin mu = m/s for phase angles greater than 90 degrees) and was taken as a measure of TAA. Lung resistance RL and elastance EL were calculated from esophageal pressure (Pes), mouth pressure, tidal volume, and tidal flow. All infants displayed TAA at baseline. After BD administration, TAA decreased in those infants in whom RL decreased. The percentage decrease in the phase angle from baseline after BD administration was significantly correlated with the decrease in peak-to-peak Pes (delta Pes) and the percentage decrease in RL and EL. We conclude that AO in infants leads to TAA through altered pleural pressure swings acting on the compliant chest wall. Changes in lung mechanics induced by bronchodilators are reflected in changes in TAA.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗
PubMed1990

Pericardial effects of diastolic ventricular interaction during development.

The effects of the pericardium on myocardial diastolic ventricular interaction during early development were determined in vitro using hearts excised from eight preterm (109 +/- 0.106 SE d gestation; term = 147 d) and eight newborn (2.3 +/- 0.30 SE d postnatal age) lambs. The lamb hearts were excised with the pericardium intact and immersed in a cold cardioplegic solution. Subsequently, very compliant balloon catheters were inserted into the right and left ventricles retrograde through the pulmonary artery and aorta respectively. Before and after the removal of the pericardium, the changes in left ventricular pressure or volume caused by increasing right ventricular pressure or volume were measured. Computerized analysis of the pressure and volume recordings yielded pressure and volume transfer functions that quantified ventricular interaction. The pressure transfer functions (left ventricular pressure/right ventricular pressure) both with and without the pericardium intact were 0.297 +/- 0.010 SE and 0.140 +/- 0.005 SE, respectively, for the preterms and 0.650 +/- 0.033 SE and 0.301 +/- 0.031 SE for the newborns. The volume transfer functions (left ventricular volume/right ventricular volume) with and without the pericardium were 0.320 +/- 0.04 SE and 0.150 +/- 0.024 SE, respectively, for the preterm and 0.514 +/- 0.052 SE and 0.233 +/- 0.027 SE for the newborns. These data demonstrate that 1) the pericardium increases ventricular interaction in both preterm and newborn lambs and 2) the relative percentage increase is similar for both age groups and not age dependent. Furthermore, these findings suggest that the increase in ventricular interaction due to the presence of the pericardium is mediated by the relative compliances of the free walls, septum, and pericardium.

Animals↗
PubMed1990

Effect of exchange transfusion with a red blood cell substitute on the neonatal lung.

The present study was designed to evaluate the acute effects of a perfluorocarbon erythrocyte substitute on cardiopulmonary function in the newborn lamb. Isovolemic double volume exchange transfusions were performed with the perfluorocarbon emulsion (FC-43) during controlled ventilation and acid-base status. Cardiopulmonary function was determined pre (control) and post (exchange) exchange transfusion. As expected with perfluorocarbon transfusion, hematocrit decreased (from 31.3 +/- 1.35% to 6.7 +/- 0.8%, SEM, P less than 0.001) and fluorocrit increased (from 0 to 17.8 +/- 2%, P less than 0.001). These changes in blood composition were associated with a significant increase in arterial oxygen tension (from 317.0 +/- 22 mmHg to 419.0 +/- 22 mmHg, P less than 0.001) and decrease in arterial oxygen content (from 14.0 +/- 8 ml O2/dl blood + PFC to 5.4 +/- 0.3 ml O2/dl blood + PFC, P less than 0.001), A-a oxygen gradient (from 357.0 +/- 23 mmHg to 255.0 +/- 23 mmHg, P less than 0.001) and viscosity (from 3.4 +/- 0.1 cps to 2.1 +/- 0.1 cps, P less than 0.001). No significant change in lung mechanics or hemodynamics was observed. These preliminary data demonstrate cardiopulmonary and hemodynamic stability immediately following transfusion with perfluorocarbon emulsion and outline physiological responses associated with transfusion of perfluorocarbon emulsions, a potential adjunct to neonatal therapeutics.

Airway Resistance↗
PubMed1990

Liquid ventilation during early development: theory, physiologic processes and application.

Clinical statistics indicate that extrauterine viability becomes increasingly compromised at earlier gestational ages. It is generally accepted that this trend is largely due to the immaturity of the pulmonary system. Investigators have attributed the high degree of instability during the perinatal period of the preterm infant to incomplete biochemical development of the lung. Whereas disruption in biochemical development results in alveolar surfactant deficiency, elevated interfacial tension, alveolar instability, and inadequate pulmonary gas exchange, it is possible that incomplete development of other components within the pulmonary as well as other organ systems may also influence ultimate extrauterine viability of the preterm neonate. However, until recently, little was known in this regard as conventional gas ventilation techniques have been unsuccessful in supporting a stable animal preparation for controlled experimental investigation of physiologic processes before approximately 85% gestation. In the early 1970s, the concept of liquid ventilation was applied to the preterm and newborn animal. Since this time, technological advances in liquid delivery systems have established this experimental approach as a viable means to support the preterm infant during the transition from the liquid-filled intrauterine to gas-filled extrauterine environment. Reduction of surface tension, improvement in lung mechanics, effective pulmonary gas exchange, acid-base balance, improved distribution of pulmonary blood flow, and cardiovascular stability in the liquid ventilated preterm animal support the use of this alternative method of ventilation as a valuable experimental tool and potential clinical therapeutic modality during early development. The evolution of this approach is presented in this article.

Animals↗
PubMed1989

Mechanics and energetics of breathing in newly diagnosed infants with cystic fibrosis: effect of combined bronchodilator and chest physical therapy.

Response to bronchodilator (BD) and chest physical therapy (CPT) was evaluated in newly diagnosed infants with cystic fibrosis (n = 13; age, 6.9 +/- 1.5 SE months) who were asymptomatic for lung disease at the time of the study. Lung function was assessed from the mechanics and energetics of breathing prior to and following combined BD and CPT. After therapy, respiratory rate, tidal volume, minute ventilation, and pulmonary compliance were not statistically different from values under baseline conditions. In contrast, there was a significant decrease in pulmonary resistance (-34%; P less than 0.05) and the resistive work of breathing (-26%; P less than 0.05) following the combined treatment. The effect of combined BD and CPT in decreasing the resistive respiratory load may be related to relief of subclinical bronchospasm, reduction in mucosal edema, and mobilization of mucous secretions.

Bronchodilator Agents↗
PubMed1989

A comparison of preterm and adult airway smooth muscle mechanics.

To determine whether airway smooth muscle undergoes a maturational change regarding force generation, length-tension relationships were determined in isolated trachealis strips from adult and preterm sheep. At the length of maximum force generation, passive active and total tensions of the adult muscle were 2.5 times greater than preterm values (P less than 0.001). KCl stimulation yielded a greater peak tension in the adult strips than in the preterm strips (P less than 0.01). Preterm strips required higher concentrations of KCl to initiate contractions and higher concentrations to reach peak tension. Acetylcholine- (ACh) induced contraction resulted in greater force development at each dose in the adult strips compared with preterm strips (P less than 0.001). The dose of ACh required to reach a half-maximal response was significantly less for the adult strips than for the preterm strips (P less than 0.005). These data demonstrate that both force generation and receptor sensitivity increase with age. This inability of immature smooth muscle to generate as much force as adult smooth muscle may help explain why very preterm neonates requiring intermittent positive-pressure ventilation are at risk for developing structural airway problems.

Aging↗
PubMed1989

In vivo mechanical properties of the developing airway.

The inherent mechanical characteristics of the airways are determined in part by their elastic and viscoelastic properties. As compliant structures during early development, the airways are susceptible to significant distention and collapse, depending on the proportionality between airway volume and transmural pressure. To characterize the age-related changes in airway mechanical properties, the elastic and viscoelastic behavior of in vivo tracheal segments were evaluated in preterm and newborn lambs over a wide range of developmental age (108 to 154 days postconceptional age). Tracheal pressure-vol relationships and concomitant airway compliance measurements were used to determine elastic behavior. Calculations of the tracheal relaxation time constant on the same tracheal segments were used to evaluate airway viscoelastic behavior. Data demonstrated a significant (p less than 0.01) correlation with developmental age. With increasing age, the airways were found to be less compliant, and the tracheal relaxation time constant was observed to decrease. The difference in elastic properties of the trachea, in vivo compared to in vitro, suggest that neural-humoral and surrounding connective tissue factors may affect the elasticity of the developing airway. Although the modulating effects of smooth muscle tone and supporting connective tissue assist in the control of airway dimension and resistance to airflow in the intact airway, the age-related differences in the elastic properties may be a factor that predisposes the more immature airway to positive pressure-induced damage.

Animals↗
PubMed1989

Developmental differences in tracheal cartilage mechanics.

Length-tension characteristics were examined in tracheal rings excised from preterm lambs (n = 8) and adult sheep (n = 7) to determine developmental differences in the mechanical properties of tracheal cartilage. Tension was measured in both the complex (comprised of the pars membranacea and its cartilagenous insertion) and the cartilage alone (by severing the pars membranacea) as the ring was lengthened so as to increase the distance between the points of insertion. Analysis of regression lines show significantly greater slopes for both the complex and the cartilage in the adult group compared to the preterm group. These data reveal that age-related differences in tracheal cartilage mechanics parallel and may contribute to age-related differences previously determined in tracheal compliance.

Age Factors↗
PubMed1989

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↗
PubMed1989

Effects of intravenous perfluorocarbon and oxygen breathing on acute decompression sickness in the hamster.

Anesthetized female hamsters (Mesocricetus auratus) were divided into 3 experimental groups with 16 animals in each group. After control arterial blood pressure and ECG recordings, the animals were placed in a hyperbaric chamber for 30 min at 7 ATA and then decompressed directly to the surface at a rate of 60 fsw/min. After their removal from the chamber, animals were either not treated (group 1); given i.v. saline while breathing 100% oxygen (group 2), or given i.v. oxypherolperfluorochemical (Fluosol-43) perfusion emulsion while breathing 100% oxygen (group 3). Thirty minutes after decompression, all but one of group 1 had died (a 6% survival rate). Group 2 had a 62% survival rate and group 3 had a 94% survival rate. Perfluorochemicals were observed to reduce the number of bubbles formed, enhance bubble disappearance, and reduce dysrhythmias.

Animals↗