Biomedical subjects

T H Shaffer

Publications and source records attributed to T H Shaffer.

At least 109 records · Page 6Linked to original sources

PubMed1988

Evaluation of neonatal pulmonary mechanics and energetics: a two factor least mean square analysis.

Pulmonary mechanics, using a two factor least mean square analysis technique, were determined in 22 preterm neonates with respiratory failure. The respiratory system is modelled as a linear mechanical system. Concurrent signals of airflow and transpulmonary pressure were utilized to calculate values of dynamic lung compliance and pulmonary resistances; these determinations were made over the entire tidal volume range. In addition, values of resistive work of breathing, pulmonary time constants, scalar records of sequential breaths, pressure-volume and flow-volume relationships were available for data review and interpretation. The mean +/- SEM value of tidal volume was 7.4 +/- 0.6 ml/kg; dynamic lung compliance was 0.44 +/- 0.04 ml/cmH2O/kg; and the pulmonary resistance of the whole breath was 106 +/- 9.1 cmH2O/liter/s. The resistive work of breathing (hysteresis) was 41.8 +/- 5.9 gm.cm/kg. In correlating the measured values of pressure and flow to those predicted by the model, the mean value of the correlation coefficient for the least mean square analysis for all 22 studies was 0.995 +/- 0.001; the standard error of estimate of the predicted pressure was less than 4.4% of the range of pressures measured. Thereby, the model was considered to be appropriate for the neonatal respiratory system. In addition to the traditional procedures of evaluating the respiratory status of a sick neonate, bedside analysis of pulmonary mechanics provide graphical information, and quantitative data which should be useful in day-to-day pulmonary management.

Computer Simulation↗

PubMed1988

Influence of smooth muscle tone and longitudinal tension on the collapsibility of immature airways.

Mechanical properties and pressure-flow relationships of tracheae excised from very premature lambs were studied in a plethysmograph. Control (Group I) data revealed the tracheae to be extremely compliant, collapsible airways, with an inflation compliance (Si) of 0.033 (+/- 0.004 SE) mmHg-1, collapsing compliance (Sc) of 0.026 (+/- 0.001 SE) mmHg-1, and pressure-flow relationships similar to those of a Starling resistor. Acetylcholine administration (Group II) lowered both Si, 0.026 (+/- 0.003 SE) mmHg-1 and Sc, 0.022 (+/- SE) mmHg-1, as did longitudinal stretch (Group III): Si, 0.021 (+/- .003 SE) mmHg-1, and Sc, 0.017 (+/- 0.002 SE) mmHg-1. Alterations in tracheal collapsibility were also evidenced by significant reductions in resistance to airflow when the tracheae were subjected to compressive forces. Altering both smooth muscle tone (acetylcholine administration) and longitudinal length simultaneously (Group IV) produced results similar to those obtained for Group III. These data help to define the functional characteristics of immature airways and may provide insight for more effective clinical management of the premature infant.

Acetylcholine↗

PubMed1988

Effect of tracheal smooth muscle tone on collapsibility of immature airways.

To test the influence of smooth muscle tone on extremely immature airways, tracheal segments (n = 19) were excised from premature lambs at 114-121 days gestation and mounted in a chamber filled with Krebs solution. Inflation (Si) and collapsing (Sc) compliance were determined by altering transmural pressure from 30 to 0 Torr and -30 to 0 Torr, respectively, both during control (C) and after acetylcholine (ACh) administration (experimental, E). Flow (V = 2-15 l/min) was then introduced through the tracheal lumen while chamber pressure (Pc) was increased from 0 to 30 Torr and driving pressure (Pd) was recorded for both C and E conditions. Tracheae were found to be extremely compliant; both Si and Sc were significantly (P less than 0.005) lower after ACh administration. Resistance to airflow (R = Pd/V) was also significantly (P less than 0.05) lower after ACh administration at each compressive pressure and each flow value. These results suggest that the highly compliant preterm trachea exhibits pressure-flow characteristics similar to a Starling resistor, and the effects of compressive pressures may be attenuated by ACh-induced smooth muscle contraction. Comparison of these results with data from adult and newborn animals suggests a developmental difference in tracheal mechanics and pressure-flow relationships, as well as in the way airway function is altered by smooth muscle stimulation.

Acetylcholine↗

PubMed1988

A new experimental approach for the study of cardiopulmonary physiology during early development.

In this report, an experimental approach and newly designed apparatus for liquid ventilation of preterm animals are described. Findings of age-related changes in cardiopulmonary function of this animal preparation are presented. Thirty-one lambs, 102-137 days gestation (term 147 +/- 3 days), were studied. The carotid artery, jugular vein, and trachea of the exteriorized fetus were cannulated under local anesthesia. Immediately after cesarean section delivery, ventilation commenced; warmed (39 degrees C) and oxygenated (PIO2 greater than 500 Torr) liquid fluorocarbon (RIMAR 101) was delivered to the lung by a mechanically assisted liquid ventilation system. Skeletal muscle paralysis, low-dose exogenous buffering, and thermal support were maintained during the 3-h experiment. Pulmonary gas exchange, acid-base status, and cardiopulmonary and metabolic function were assessed. By utilizing these techniques, effective arterial oxygenation, CO2 elimination, acid-base status, and cardiovascular stability were supported independent of gestational age. The results demonstrate a developmental increase in specific lung compliance and mean arterial pressure and decrease in heart rate and systemic O2 consumption per kilogram with advancing gestational age. These findings demonstrate that liquid ventilation negates the dependency of effective pulmonary gas exchange on surfactant development, thereby extending the limits of viability of the immature extrauterine lamb. As such this new experimental approach is useful for the study of physiological development over an age range previously limited to fetal animal preparations and, therefore, may provide insight regarding adaptation of the premature to the extrauterine environment.

Animals↗

PubMed1988

Developmental changes in diastolic ventricular interaction.

Developmental changes in the myocardial diastolic ventricular interaction of hearts excised from 12 preterm (126 +/- 0.8 SE days gestation; term = 147 days) and eight newborn (2.5 +/- 0.2 SE days postnatal age) lambs were evaluated in vitro. The excised hearts were immersed in a cold cardioplegic solution during which time compliant balloon catheters were inserted into the right and left ventricles through the pulmonary artery and aorta, respectively. The catheters were alternately connected to an infusion pump and appropriate transducers in order to obtain simultaneous biventricular pressure and volume measurements as the volume of each ventricle was varied. Computerized analysis of the pressure and volume recording was used to determine right and left ventricular free wall compliance, ventricular septal compliance, and pressure and volume transfer functions. Ventricular septal compliance was significantly less than the free wall compliances within both groups. Ventricular septal compliance (p less than 0.05) and transfer functions (p less than 0.05) in the preterm were significantly lower than in the newborn. No significant differences in ventricular free wall compliances were found between or within age groups. These findings demonstrate an increase in ventricular coupling and functional interaction with development, potentially attributable to an increase in septal compliance with development.

Animals↗

PubMed1988

Effect of ventilation on mechanical properties and pressure-flow relationships of immature airways.

Ventilation of immature airways has been shown to result in pressure-induced deformation and alteration of mechanical properties. These changes in mechanical properties may alter the effect of compressive pressures on pressure-flow relationships. To test this hypothesis, unventilated (Group I, n = 8) and ventilated (group II, n = 8; mean pressures of 8-12 cm H2O for 2 h duration) tracheal segments were excised from preterm lambs approximately 118 days gestation and mounted in a Krebs-filled chamber for determination of compliances and pressure-flow relationships. Compliance data were obtained for both the inflation loop (inflation compliance) and the collapsing loop (collapsing compliance) of the pressure-volume curve for each segment. Flow (V = 2-10 liter/min.) was introduced through the lumen of each segment at different chamber pressures (Pc = 5-30 mm Hg). Driving pressure (Pd) was recorded for each V and Pc. Airway resistance (R) was calculated as Pd/V. Group II had significantly greater (p less than 0.005) radii than Group I, suggesting ventilation-induced deformation. Group II had significantly lower (p less than 0.05) inflation compliance but significantly greater (p less than 0.05) collapsing compliance than group I. Two-factor analysis of variance demonstrated significantly greater (p less than 0.05) R in group II at each value of V and each Pc. These data may help to explain the flow limitation and gas-trapping observed in preterm infants who have been mechanically ventilated.

Animals↗

PubMed1988

Fluorocarbon ventilation: maximal expiratory flows and CO2 elimination.

Elimination of CO2 during liquid ventilation is dependent on flow, diffusion, and the liquid's capacitance for CO2. Maximum expiratory flow (Vmax) and diffusion dead space were measured in vivo in 12 young cats during liquid fluorocarbon (FC-80) ventilation to determine the effect of breathing frequency on maximum CO2 elimination. All animals were maintained (PaO2 = 255 +/- 19 SEM mm Hg, PaCO2 = 35 +/- 1 SEM mm Hg, pH = 7.31 +/- 0.01 SEM) within physiologic range during 1-4 h of liquid ventilation. The Vmax in air (26 +/- 1 SEM liter/min) and in liquid (1.2 +/- 0.2 SEM liter/min) was determined by volume displacement plethysmography. Diffusion dead space (VDdiff) during liquid ventilation as a ratio of alveolar volume (VA) was well correlated (r = 0.84, p less than 0.005) with the average time (tav) the liquid was in the lung [VDdiff/VA = 0.89 e (-0.053 tav)]. Alveolar ventilation, CO2 elimination (VCO2), and PaCO2 were not affected by breathing frequency (f) when tidal volume was adjusted appropriately during steady state liquid ventilation. Predicted maximum CO2 elimination (VCO2max) determined from Vmax and VDdiff was 24 ml/min at a f of 3-3.5 breaths/min. The maximum was found to be strongly dependent on f with much less dependency on fixed dead space (anatomic plus equipment) and wave shape characteristics. Elimination of CO2 decreased at low values of f due to inadequate ventilation and at high values of f due to inadequate diffusion time. From a comparison of experimentally determined steady state VCO2 to theoretically predicted VCO2max, the results demonstrate a f-related functional reserve capacity for CO2 elimination during liquid ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

A brief review: liquid ventilation.

The liquid-filled lung preparation has provided physiologists with a unique technique for varying the physical properties of respiratory media and studying their effect on basic pulmonary processes. More recently, liquid breathing, ventilation of the lungs with an oxygenated fluid, has extended the applicability of the liquid-filled lung to include a wide variety of environmental and clinical research areas. This article is an account of the history of liquid breathing based on a review of 60 publications dating back to 1920. The physiologic status of this experimental preparation has continuously advanced due to technical changes in experimental approach and improved understanding of the implications of fluid breathing on overall systemic physiology. In this regard, the evolution of the liquid breathing concept from the saline-filled lung to ventilation with inert liquids is presented. Emphasis is placed on how liquid breathing can be used as an effective research tool for expanding our understanding of normal respiratory physiology and how this technique may be of benefit to other areas of science. Finally, like most techniques in biological investigations, liquid ventilation has certain limitations. Therefore, this review summarizes the rationale behind various experimental approaches, the nature and tractability of limitations, and the results which can be safely drawn from experimental studies to date.

Animals↗

PubMed1986

Acquired tracheomegaly in very preterm neonates.

Proximal airways are compliant structures at early gestational ages and may be susceptible to pressure-induced deformation following prolonged ventilatory support. Sixteen neonates (mean +/- SD gestational age, 27.0 +/- 0.6 weeks; mean +/- SD birth weight, 847 +/- 68 g) were studied to assess tracheal volume deformation. The neonates received ventilatory support for a mean +/- SD duration of 25.4 +/- 4.9 days. During this period the maximum peak inspiratory pressures ranged from 15 to 25 cm H2O, and respirations ranged from 20/min to 60/min. These neonates were studied at seven days postextubation and were individually matched for body weight with 16 nonventilated neonates. The width of the tracheal air column was measured at the lower border of the first thoracic (T-1) and third thoracic (T-3) vertebrae. The average tracheal width (average of T-1 and T-3) was significantly (38%) wider in the ventilated group, and the mean +/- SD tracheal width values were 3.79 +/- 0.29 mm, as compared with the control values of 2.74 +/- 0.31 mm. Based on these data it was estimated that the tracheal volume was 91% greater in the ventilated group. These observations demonstrate tracheal volume deformation and acquired tracheomegaly in neonates who have received mechanical ventilatory support. In addition to increased dead space ventilation, these findings also indicate underlying mechanical deformation of the tracheal wall.

Barotrauma↗

PubMed1986

A new approach to induced hypothermia.

A variety of methods have been employed for the induction of hypothermia; however, there are still some inherent problems that remain with current techniques. Liquid ventilation, a process used in several other environmental and clinical research areas, may be a feasible method since it takes advantage of the effectiveness of the pulmonary architecture as a heat exchanger. Hypothermia induced by liquid ventilation was studied in 8 newborn lambs, mean age = 10 +/- 8 SEM days. Each lamb was anesthetized with sodium pentobarbitol (20 mg/kg) and intubated. Cardiopulmonary measurements were taken during a control period prior to induced hypothermia. Liquid temperatures of 20 and 30 degrees C were used in cooling the animal while monitoring rectal and surface temperatures. Temperatures decreased producing rectal cooling rates of 8.4 and 4.8 degrees C/hr, respectively. Blood gas analysis showed adequate physiological gas exchange for all lambs during the liquid ventilation period. Based on the data, the process of liquid ventilation offers a unique potential both in experimental and clinical areas as a new approach to the technique of induced hypothermia.

Animals↗

PubMed1986

Pulmonary vascular resistance in the fluorocarbon-filled lung.

Pulmonary vascular resistance was investigated in the fluorocarbon-filled lung in an in situ isolated lung preparation. Lungs were perfused at constant flow (100 ml X min-1 X kg-1) with whole blood from a donor cat. left atrial pressure was held constant at zero pressure. Measurements of pulmonary arterial pressure enabled calculation of pulmonary vascular resistance. Regional changes in pulmonary blood flow were determined by the microsphere technique. During quasi-static deflation over a range of 0-30 mmHg, dependent alveolar pressure was consistently greater for a volume of fluorocarbon than for gas, with each pressure-volume curve for the fluorocarbon-filled lung shifted to the right of the curve for the gas-filled lung. In turn, pulmonary vascular resistance was found to increase linearly as a function of increasing alveolar pressure, independent of the medium in the lung. Thus, for a given volume, pulmonary vascular resistance was consistently greater in the fluorocarbon-filled lung compared with the gas-filled lung. This increase in pulmonary vascular resistance was accompanied by a redistribution of pulmonary blood flow in which blood flow to the dependent region was decreased in the fluorocarbon-filled lung compared with the gas-filled lung. Conversely, the less-dependent regions of the lung received a relatively greater percentage of blood flow when filled with fluorocarbon compared with gas. These findings suggest that pulmonary vascular resistance is increased during liquid ventilation, largely as the result of mechanical interaction at the alveolar-vascular interface.

Analysis of Variance↗

PubMed1986

The effect of tracheal smooth muscle tone on neonatal airway collapsibility.

The effect of smooth muscle tone on the functional characteristics of neonatal airways was studied in six newborn lambs. Tracheal mechanics, resistance, and collapsibility were determined in tracheal segments of uniform length which were surgically isolated just caudal to the cricoid cartilage. Resistance to airflow through uncompressed (zero transmural pressure) and compressed (increased transmural pressure) trachea was evaluated over a range of physiological flows both before and after induced contraction of airway smooth muscle. Results demonstrate that neonatal tracheal smooth muscle does respond to cholinergic stimulation and that there was a significant decrease in airway compliance. Furthermore, the consequent increase in airway rigidity may play a role in resisting collapse or compression of the intrathoracic airway during expiration.

Airway Resistance↗

PubMed1986

The role of tracheal smooth muscle contraction on neonatal tracheal mechanics.

The ability of tracheal smooth muscle tone to modulate the mechanical properties of neonatal airways was evaluated in six newborn lambs. Tracheal pressure-volume relationships, isovolumic compliance, hysteresis, and the relaxation time constant of the smooth muscle were evaluated as a function of incremental cholinergic stimulation. Tracheal active tensions were also determined at the graded levels of cholinergic stimulation. Data show that a maximal cholinergic stimulation resulted in a mean developed active tension value of 14.3 +/- 2.13 SEM X 10(3) dynes/cm. The resultant 55% decrease in tracheal compliance was linearly correlated to the increase in active tension (r = 0.90, p less than 0.01). Cholinergic stimulation also resulted in a 18.4% decrease (p less than 0.02) in the relaxation time constant of the smooth muscle, and in a 82% increase (p less than 0.01) in tracheal hysteresis. This study demonstrates that both elastic and viscoelastic properties of the neonatal lamb trachea are effected by tracheal smooth muscle contraction. Since neonatal airways are more compliant than adult airways, cholinergic stimulation could conceivably enhance airway rigidity and may provide a protective mechanism against pressure-induced deformation.

Animals↗

PubMed1985

Preterm infants: ventilation and P100 changes with CO2 and inspiratory resistive loading.

The ventilatory effects of inspiratory flow-resistive loading and increased chemical drive were measured in ten neonates during progressive hypercapnia in control and loaded states. Hypercapnia (mean increase PCO2 = 15-20) resulted from inspiring 8% CO2 in room air and inspiratory loading by a flow-resistive load = 100 cmH2O X l-1) X s. Hypercapnia produced an increase in group minute ventilation secondary to increasing tidal volumes and breathing frequencies. Loading shifted the minute ventilation-CO2 response to the right, and slopes decreased significantly (P less than 0.05) consequent to a significant decrease in the frequency-CO2 slopes (P less than 0.05), which became negative in four of the ten subjects. Mouth pressure measured at 100 ms after onset of inspiratory effort (P100) occlusion pressure-CO2 slopes measured in five subjects showed no significant increase with load application. Resistive loading produced significant increases in inspiratory time (P less than 0.02) and the inspiratory time/total breath time ratio (P less than 0.01). Airway occlusion elicited the Hering-Breuer reflex, with a significant increase in inspiratory time-to-total breath time ratio (P less than 0.01). The results show that the inspiratory resistive load produced ventilatory compromise in newborns and insufficient compensatory augmentation of central drive.

Airway Resistance↗

PubMed1985

Developmental alterations in pulmonary function of the lamb.

Pulmonary function was evaluated in 40 lambs ranging in age from 106 to 161 postconceptual days. Preterm lambs were delivered by cesarean section and newborn lambs were delivered vaginally. All animals were mechanically ventilated and had indwelling catheters. Measurements of transpulmonary pressure, airflow, tidal volume and functional residual capacity enabled calculations of lung compliance, specific compliance, lung conductance and specific conductance. Regression analysis indicated that lung compliance, lung conductance and functional residual capacity increased with developmental age; whereas, specific compliance and specific conductance decreased with maturity. These data quantitate the developmental alterations in the pulmonary function of preterm, term and newborn lambs.

Aging↗

PubMed1984

Mechanics and energetics of breathing helium in infants with bronchopulmonary dysplasia.

The mechanics and energetics of breathing were studied in preterm infants with bronchopulmonary dysplasia while spontaneously breathing control gas and helium-oxygen (Heliox) gas mixtures. During Heliox breathing, there was a significant decrease in pulmonary resistance, resistive work of breathing, and mechanical power of breathing, whereas ventilation remained unchanged. Breathing a lower density gas mixture (Heliox) may have therapeutic value by decreasing the demands on the respiratory muscles and the caloric requirements for breathing. Therefore, this modality may reduce potential respiratory muscle fatigue and avail additional calories for growth and recovery in the preterm infant with bronchopulmonary dysplasia.

Bronchopulmonary Dysplasia↗

PubMed1984

Tracheal volume deformation in a developmental rabbit model.

Alterations in tracheal volume were evaluated in a developmental in vivo rabbit model during and following the application of continuous positive pressure (CPP). Sequential volume changes were recorded during 60 min of CPP to a bypassed tracheal segment. The distal trachea was utilized for spontaneous ventilation. CPP of 10 cm H2O was applied to three developmental groups: group I, 5 term newborn pups; group II, 5, 7-day-old pups, and group III, 5 adult female rabbits of 18 +/- 6 months old. Changes in tracheal volume were measured by a micropipette system. Following 60 min of CPP, tracheal volumes increased (p less than 0.01) by 39.8% in group I; 36.1% in group II and 5.1% in group III. During a recovery period (60 min), return towards initial resting volume was observed in all groups, though maximal persistent volume deformation was observed in groups I and II. Thus, these data indicate tracheal barotrauma in the form of persistent dimensional deformation at early stages of development in an in vivo rabbit model.

Animals↗

PubMed1984

Gallbladder mechanics in newborn piglets.

The mechanical properties of the newborn piglet gallbladder were evaluated in both the stimulated and unstimulated states. The pressure-volume relationships, compliance, and the estimated active tension of the gallbladder were determined in 10 newborn piglets (2-7 days of age). Agonist stimulation was achieved by administration of histamine (25 micrograms/kg/h) and cholecystokinin (CCK) (60 ng/kg/h). Both histamine and CCK increased the intracholecystic pressure at the 50% resting volume from 12.4 cm H2O to 18.9 and 15.5 cm H2O, respectively. This resulted in a significant (p less than 0.05) increase in the active tension. However, no significant changes were observed in the gallbladder compliance after stimulation. These findings characterize the mechanical properties of the normal neonatal gallbladder. The low magnitude of intracholecystic pressure response to agonist stimulation, when compared to adult data, may explain the occurrence of decreased neonatal choledochal bile flow.

Animals↗