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Biomedical subjects

M R Wolfson

Publications and source records attributed to M R Wolfson.

At least 109 records · Page 6Linked to original sources

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↗

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↗

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↗

Computerized stripping method for multiple nuclide microsphere studies.

Radiolabeled microspheres are commonly used to measure cardiac output and regional blood flow distribution in small animals such as rats. By using batches of microspheres labeled with different nuclides, several flow measurements can be made in the same animal. A protocol and computer program for analyzing data from multiple nuclide microsphere experiments are described. This protocol is designed to reduce the amount of arterial blood which must be withdrawn during microsphere distribution and eliminate the potential loss of data due to contamination of reference samples by nuclides used in previous flow measurements.

Animals↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Physiological effects of ventilation with liquid fluorocarbon at controlled temperatures.

Body cooling, respiratory heat loss, and the physiological effects of liquid ventilation at various temperatures were studied in 10 adult cats with applications to the deep sea diver. The animals were stabilized on mechanical gas ventilation with 100% oxygen during a control period and then mechanically ventilated for 1 h with liquid fluorocarbon. Fluorocarbon (Rimar 101) temperatures of 10 degrees C, 20 degrees C, and 30 degrees C were used to ventilate the animals while rectal and subcutaneous body temperatures were being measured. For the 3 temperature conditions, respective cooling rates of 9.0 degrees C/h, 7.8 degrees C/h, and 3.6 degrees C/h, as well as respiratory heat losses of 65,637 J X kg-1 X h-1, 33,488 J X kg-1, X h-1, 18,036 J X kg-1 X h-1 were observed while maintaining effective physiological gas exchange [mean PaO2 = 353 +/- 28 (SEM) mmHg, mean PaCO2 = 30 +/- 2 (SEM) mmHg]. Changes in cardiovascular variables were noted as mild (35 degrees C-30 degrees C) and moderate (30 degrees C-25 degrees C) levels of hypothermia were reached. Cardiac output, oxygen consumption, heart rate, and mean blood pressure were significantly correlated with rectal temperature. The data presented herein quantitate the effects of liquid ventilation on body cooling and respiratory heat loss. Furthermore, the physiological alterations associated with the observed hypothermic condition could severely limit the effectiveness of a human diver if not carefully controlled.

Animals↗

Respiratory muscle function, assessment, and training.

This article presents a brief overview of respiratory muscle mechanics and the effects of lung disease and neuromuscular disease on pulmonary function. A variety of current specific and general muscle training techniques are described and discussed. Also presented is a current review of training studies and the effects of muscle training on cardiopulmonary function, muscle strength, endurance and fatigue, and exercise tolerance.

Adult↗

Passive hemolysis by serum and cobra venom factor: a new mechanism inducing membrane damage by complement.

The studies presented here indicate that activation of the complement (C') system by a foreign protein will cause membrane injury and passive lysis of unsensitized erythrocytes present at the time of the reaction. These observations suggest that in addition to the classical antibody-C'-induced cytolysis, there are alternative pathways or mechanisms for activation and participation of the terminal C' components in the production of cell membrane injury. We have shown that a substance derived from cobra venom and eluted from a single protein band on polyacrylamide can promote lysis of unsensitized autologous or heterologous erythrocytes in the presence of fresh guinea pig serum and that this lysis-inducing activity and C'-inhibiting activity appear to reside in the same fractions. The lytic activity is prevented by several agents known to impair classical C'3 activity, but is unaffected by certain procedures which interfere with the function of C' components C'1 and C'2, a suggestion that this reaction involves chiefly C'3-C'9. Further, the cobra venom (CV) factor depletes C' activity in cobra serum, and the CV factor (with its 5S serum cofactor) converts purified C'3 to its inactive form,(1) indicating that the reaction of this complex with the complement system occurs without participation of antibody. Therefore, since the lysis-inducing and C'-inhibiting activity of the CV factor appear to result from similar interactions with the complement system, these observations suggest that cell membrane damage and cell lysis can be accomplished through activation of the complement system by a mechanism involving little or no participation of classical antibody or C' components C'1, 4, or 2.

Animals↗

Antenatal triiodothyronine improves neonatal pulmonary function in preterm lambs.

OBJECTIVE: To characterize 1) pulmonary gas exchange, 2) pulmonary function, 3) lung fluid and tissue phospholipid content, and 4) thyroid hormone in the premature lamb (0.85 of term) after intra-amniotic administration of 100 micrograms of triiodothyronine (T3) 2 weeks before delivery. METHODS: Nine fetal lambs were given 100 micrograms of intra-amniotic T3 under ultrasound guidance at 112 +/- 1 days' gestation and delivered at 126 +/- 1 days (term = 149 days). Five saline-injected animals served as controls. Arterial blood gases, pulmonary mechanics, and lung volumes were compared between groups for 1 hour after delivery. At delivery, tracheal fluid and blood was taken for T3, and thyroxine (T4) levels. Tracheal fluid and lung tissues were assayed for total phosphorus and disaturated phosphatidylcholine. RESULTS: Triiodothyronine-treated lambs had significantly higher mean arterial pH and lower PCO2 than controls (P < .05) with a trend toward higher mean PO2. The dynamic lung compliance was increased by 54% with a 40% proportional increase in tidal volume and minute ventilation in the T3-treated group (P < .05). Functional residual capacity increased 69% (P < .05) without a change in specific compliance. The tracheal fluid and pulmonary phospholipids and tracheal fluid and plasma T3 and T4 levels were not different between the two groups. CONCLUSION: A single 100 micrograms dose of antenatal T3 significantly improves neonatal gas exchange and lung compliance. The improvement in lung function was not accompanied by an increase in pulmonary surfactant production. It is inferred that T3 improved lung function via accelerated structural development of the lung with an alternative possible effect on parenchymal connective tissue matrix.

Amniotic Fluid↗

Thermal stability and transition studies with a hybrid warming device for neonates.

OBJECTIVE: The use of both warmer beds and incubators is common in neonatal intensive care units (NICU), and transferring between these two warming devices is a routine and necessary event. This study was designed to evaluate the efficacy of a new hybrid-warming device, the Versalet, in transitioning a preterm animal from a warmer bed to an incubator mode and back. STUDY DESIGN: Nine premature lambs were randomized, following delivery, to receive thermal support from a conventional warming bed and an incubator (control group), or from the Versalet (study group) in the warmer bed and incubator modes. Core and various surface temperatures, as well as physiological parameters were measured first during warming in the radiant warmer bed mode, Versalet or Resuscitaire and then during transition to the incubator mode, Versalet or Isolette, and then back to the warmer bed mode. RESULTS: The animals remained stable during all the transitions. Despite careful planning, adverse events occurred in the control group during transfers. There were no significant differences in the temperature or physiologic profiles during any of the transitions in either group. CONCLUSION: Compared with the standard warming technique used in NICUs (separate warmer bed and incubator), the Versalet provides similar thermal and cardiovascular stability without adverse events during transition to different modes of warming. The degree to which this device would contribute to ease of management and improved outcomes in humans needs to be evaluated in a clinical trial.

Animals↗