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Biomedical subjects

T G Mundie

Publications and source records attributed to T G Mundie.

At least 19 recordsLinked to original sources

Preservation of pulmonary function in the ventilated neonatal piglet with normal lungs.

Little attention has been focused on the progressive pulmonary deterioration which occurs in mechanically ventilated infants with normal or mildly abnormal lungs. We hypothesized that lung function would deteriorate over a 24-hr period in anesthetized neonatal piglets with normal lungs mechanically ventilated at 2 cm H2O PEEP (2PEEP group). We further hypothesized that an intermittent lung inflation procedure consisting of 15 out of 60 min of increasing lung distention (4, 8, 12 cm H2O PEEP), with the remaining 45 min at 2 cm H2O PEEP (Inflation group) would prevent this deterioration in lung function, similar to piglets mechanically ventilated continuously at 6 cm H2O PEEP (6PEEP). Results indicate that 2PEEP piglets experienced progressive deterioration in lung function, including dynamic lung compliance (-42%) and lung resistance (+55%). In contrast, inflation piglets and 6PEEP piglets had no deterioration in lung function. Hemodynamics were similar between groups, although they were the most stable in the 6PEEP group. Histopathological changes were not significantly different. We conclude that (1) prolonged mechanical ventilation at 2 cm H2O PEEP in neonatal piglets resulted in progressive deterioration in pulmonary function, (2) intermittent lung inflation or continuous 6 cm H2O PEEP prevented deterioration, and (3) functional changes occurred without changes in histopathology. Lung inflation strategies other than PEEP can be used to prevent deterioration in lung function which accompanies prolonged mechanical ventilation in anesthetized nonspontaneously breathing piglets with normal lungs.

Analysis of Variance

Continuous negative extrathoracic pressure and positive end-expiratory pressure. A comparative study in Escherichia coli endotoxin-treated neonatal piglets.

Recent clinical studies have suggested that improvement in pulmonary gas exchange with the use of continuous negative extrathoracic pressure (CNEP) in conjunction with intermittent mandatory ventilation (IMV) may be due to increased pulmonary blood flow. Accordingly, we investigated the effects of CNEP vs positive end-expiratory pressure (PEEP) in ventilated neonatal piglets after Escherichia coli endotoxin was administered to induce pulmonary hypertension. Two experimental groups of piglets with six in each, were subjected to three 30-min alternating periods--6 cm H2O CNEP with 6 cm H2O PEEP, beginning 2 h after endotoxin infusion. End-expiratory lung volume (EELV) increased similarly from baseline (13 +/- 2 mL/kg) with both CNEP (28 +/- 2 mL/kg) and PEEP (29 +/- 2 mL/kg). In addition, the increase in PaO2 from baseline with CNEP (106 +/- 9 to 135 +/- 7 mm Hg) was similar to that with PEEP (114 +/- 11 to 132 +/- 6 mm Hg). Further, no differences were found in dynamic lung compliance, EELV, lung resistance, blood gas indexes, or hemodynamics, including transmural pulmonary artery pressure and pulmonary vascular resistance between CNEP and PEEP. With transpulmonary pressure and transrespiratory pressure equal, CNEP in tandem with IMV is physiologically equivalent to PEEP and IMV.

Animals

The effects of reversing distending pressure sequences in the neonatal piglet.

We studied different sequences of lung inflation in ventilated newborn piglets with normal lungs in order to determine the effects of sequence, magnitude and duration of distending pressure on pulmonary function, and/or hemodynamics. End-expiratory pressure was varied using a continuous negative extrathoracic pressure (CNEP) device. Three groups of ventilated piglets with normal lungs were exposed to 2 cmH2O increments of CNEP from -2 to -12 cmH2O, and to decrements from -12 to -2 cmH2O, or to only -6 cmH2O. Lung inflation sequence, magnitude of inflation pressure, and duration of inflation had significant effects on end-expiratory lung volume and lung compliance at numerically equivalent pressure levels. End-expiratory lung volume and lung compliance varied (at four and five of six inflation pressures studied) by as much as 68% and 104%, respectively. Hemodynamic effects of the lung inflation sequence were more variable; those found to be different at numerically equivalent pressure levels were associated with changes in lung compliance and ventilation. Differences in pulmonary mechanics can best be explained by the effects of lung inflation on alveolar recruitment versus overinflation.

Animals

Continuous negative extrathoracic pressure versus positive end-expiratory pressure in piglets after saline lung lavage.

Recent reports have suggested that substituting continuous negative extrathoracic pressure (CNEP) for positive end-expiratory pressure (PEEP) may result in clinical benefits to infants with pulmonary disease. Other studies have suggested potential hemodynamic advantages. We compared the effects of CNEP and PEEP in 13 mechanically ventilated newborn piglets after acute lung injury induced by saline lavage. The piglets were instrumented, saline-lavaged, and exposed to 15 minute periods of incremental CNEP (-3, -6, -9, -12 cmH2O) (n = 7) or PEEP (3, 6, 9, 12 cmH2O) (n = 6). We measured and/or calculated dynamic lung compliance (CLdyn), lung resistance (RL), end-expiratory lung volume (EELV), blood gases, cardiac output (CO), heart rate (HR), transmural vascular pressures, and pulmonary and systemic vascular resistance. Pulmonary function abnormalities after saline lavage included decreased PaO2, CLdyn, EELV, and increased PaCO2 and RL (P < 0.05). Except for decreased CO, lung inflation with both CNEP and PEEP resulted in large increases in PaO2 without major pulmonary or hemodynamic effects. Other than differences in EELV at 3, 6, and 9 cmH2O distending pressure, there were no differences in pulmonary function or hemodynamics between sequences of incremental CNEP and PEEP. We conclude that CNEP and PEEP are physiologically equivalent in this model of acute lung injury.

Airway Resistance

Effect of baseline lung compliance on the subsequent response to positive end-expiratory pressure in ventilated piglets with normal lungs.

OBJECTIVE: To determine the pulmonary function and hemodynamic effects of incremental positive end-expiratory pressure in two groups of normal ventilated newborn piglets with different baseline dynamic lung compliance. DESIGN: Prospective, controlled, intervention study. SETTING: Animal laboratory. INTERVENTIONS: One group of piglets (inflation group) was prepared with 3 cm H2O (0.29 kPa) positive end-expiratory pressure and a maximal lung inflation to increase baseline lung compliance as compared with the other group (no-inflation group), prepared by 3 hrs of ventilation at zero end-expiratory pressure. Both groups were then subjected to a sequence of incremental positive end-expiratory pressures from 0 to 12 cm H2O (0 to 1.18 kPa) in 2-cm increments for 15-min periods at each level followed by a 60-min recovery period at zero end-expiratory pressure. MEASUREMENTS AND MAIN RESULTS: Pulmonary function, hemodynamic and blood gas data were collected at each positive end-expiratory pressure value and at 15-min intervals during recovery. Baseline dynamic lung compliance was 5.2 +/- 0.3 mL/cm H2O (53.04 +/- 3.06 mL/kPa) in the inflation group and 2.5 +/- 0.1 mL/cm H2O (25.5 +/- 1.02 mL/kPa) in the no-inflation group. No differences were found in any other pulmonary function, hemodynamic or blood gas value at baseline. Incremental positive end-expiratory pressure resulted in a decrease in dynamic lung compliance and an increase in end-expiratory lung volume in both groups of piglets; dynamic lung compliance was greater in the inflation group at all times. No differences were found in end-expiratory lung volume between groups. Hemodynamic changes in both groups of piglets included: decreased cardiac output and increased pulmonary vascular resistance and systemic vascular resistance. The changes in cardiac output (-23% vs. -32%), pulmonary vascular resistance (+53% vs. +95%), and systemic vascular resistance (17% vs. 51%) were less in the inflation group as compared with the no-inflation group. CONCLUSIONS: Baseline dynamic lung compliance is an important determinant of the subsequent effect of positive end-expiratory pressure on pulmonary function and hemodynamics in the ventilated piglet with normal lungs.

Animals

Methemoglobinemia induced by a benzocaine-based topically administered anesthetic in eight sheep.

Benzocaine-based anesthetic sprays are commonly used in sheep to anesthetize the nasal passages and glottis before intubation. Sprays containing benzocaine have been identified as causing methemoglobinemia in dogs, cats, and human beings. Diagnosis of benzocaine-induced methemoglobinemia was made in 8 Dorset-Finn ewes exposed to a 2-second burst of (approx 56 to 112 mg of benzocaine) anesthetic spray. Venous blood samples taken 10 to 20 minutes after intranasal application of the spray revealed methemoglobinemia of 22.6 +/- 1.8% (mean +/- SD) in 9 samples from 8 ewes. Four other ewes intentionally exposed did not have methemoglobinemia. Topical use of benzocaine-containing anesthetics in sheep is not recommended. The high methemoglobin concentration induced by this product may substantially alter the cardiovascular and pulmonary function, blood gas analyses, and exercise capacity, thereby compromising animal health and/or research results. Although it appears that minimal clinical signs are induced in healthy animals, the risks of compromising a subclinically ill animal do not offset the benefits of this product.

Administration, Topical

Effects of epinephrine, phenoxybenzamine, and propranolol on maximal exercise in sheep.

The mixed adrenergic agonist, epinephrine (10 micrograms/kg, i.v.), the beta-adrenergic receptor antagonist, propranolol (0.2 mg/kg, i.v.), or the alpha-adrenergic receptor antagonist, phenoxybenzamine (1 mg/kg, i.v.), were administered to sheep immediately before maximal incremental exercise. The effects of each of these drugs on hemoglobin (Hb) concentration during maximal exercise and on maximal exercise performance were investigated. The maximal incremental exercise protocol began at 4.0 km/h and 0% grade and finished at 5.6 km/h and 12% grade, with speed or grade increases every 1.5 minutes. Maximal exercise in control (untreated) sheep caused a mean 42% increase in hematocrit and 44% increase in Hb. This exercise-induced increase in Hb was unaffected by propranolol but was partially blocked by phenoxybenzamine. Epinephrine caused an immediate increase in Hb which abated during the early minutes of exercise and then subsequently increased toward the end of the exercise challenge. Maximum oxygen consumption (VO2) in control sheep was 47.6 +/- 6.7 ml/min per kilogram. Maximum VO2 after epinephrine, 51.6 +/- 8.7 ml/min per kilogram, was not significantly different from control. Maximum VO2 after propranolol and phenoxybenzamine, 35.4 +/- 15.3 and 40.8 +/- 8.2 ml/min per kilogram, respectively, were both significantly less than control exercise (P < 0.05).

Animals

Relationship of functional residual capacity to various body measurements in normal sheep.

Functional residual capacity (FRC) was determined by nitrogen washout in 55 normal sheep. Data on various external body measurements were collected which included body weight, chest circumference, chest width, body length, height, and sternum length. In addition, data on wet lung weight and wet lung weight/body weight ratio were collected on 10 of the sheep. A significant correlation was found between FRC and all measured parameters except height and sternum length. Multiple linear regression of all external body measurements showed the best correlation of FRC to body weight and body length, while the addition of chest circumference and/or chest width did not significantly improve the correlation. Significant deviation from the population was noted in three sheep (5.5%) that had lung weight/body weight ratios which were significantly lower than the rest of the population.

Animals

Urinary desmosine excretion as a marker of lung injury in the adult respiratory distress syndrome.

Desmosine, the intermolecular and intramolecular cross link between the chains of elastin polypeptide, may be useful as a marker of a lung injury in adult respiratory distress syndrome (ARDS). A radioimmunoassay for rabbit antibody developed against desmosine, conjugated to bovine serum albumin, can detect as little as 100 pg of desmosine in plasma or urine. Desmosine is not metabolically absorbed, reused, or catabolized by the body, but rather eliminated unchanged in the urine as low molecular weight peptides. The lung is relatively rich in elastin, and we reasoned that a timed collection could be used as an index of elastin degradation in vivo. A 2-h collection of urine for desmosine assay was obtained at the time of Swan-Ganz catheter insertion in 41 consecutive patients. On the basis of clinical and initial Swan-Ganz catheter data, the patients were assigned to one of three groups: an ARDS group (n = 12); a cardiogenic pulmonary edema (CPE) group (n = 12); and a critically ill, nonpulmonary edema group (NPE, n = 17). The mean urine desmosine concentration (mg/L) for the ARDS group (0.728 +/- 0.22 SE) differed from the CPE group (0.149 +/- 0.07; p less than 0.001). The total excretion (microgram/2 h) was 64.95 +/- 24.7 in the ARDS group and 24.71 +/- 11.7 in the CPE group (p less than 0.05). Urine desmosine concentration/serum creatinine index for the ARDS group (0.78 +/- 0.28) was greater than in the CPE group (0.07 +/- 0.04; p = 0.019). Desmosine excretion was increased in the NPE group compared with CPE and ARDS groups, possibly reflecting heterogeneity in this group. In the differentiation of ARDS from CPE, we conclude that substantial increases in urinary desmosine excretion favor a diagnosis of ARDS.

Adult

Prediction of carbon monoxide diffusing capacity of the lung in splenectomized sheep.

The steady state diffusing capacity of the lung for carbon monoxide (DLCO) was studied in 18 splenectomized adult ewes. Seven animals were anemic when studied. Weight (Wt) and, to a lesser extent, hemoglobin (Hb) level were the key predictive variables of DLCO. Sheep DLCO can be expected to range between 15 and 28 ml/min/mmHg in adult ewes which are not anemic. When DLCO measurements were repeated up to three times on the same day no significant decreases occurred. Thus, the data demonstrated no CO back-pressure caused by preceding DLCO determinations. This paper's importance is in defining a normal predictive range for this sensitive parameter of pulmonary function.

Animals

Effects of conditioning and maximal incremental exercise on oxygen consumption in sheep.

To assess the suitability of sheep for exercise studies, the effect of incremental exercise and conditioning on oxygen consumption (VO2) was studied. Six sheep were adapted to a treadmill and subsequently trained 8 weeks. The sheep were then studied, in random order, using 3 incremental exercise protocols (EX-1, EX-2, and EX-3). The protocols were chosen to approximate high (EX-1), moderate (EX-2), and low (EX-3) intensity exercise by varying treadmill speed and incline. The sheep were then conditioned for an additional 12 weeks and retested on the EX-2 protocol. During exercise, VO2, gas exchange ratio (R), and rectal temperatures (Tb) were recorded. All 3 protocols resulted in significant increases in VO2, R, and Tb (P less than 0.05). Maximum VO2 for EX-1, 49.9 +/- 5.0 ml/min/kg of body weight, was significantly greater than maximum VO2 for EX-2 and EX-3, 37.8 +/- 6.5 and 42.3 +/- 6.0 ml/min/kg, respectively (P less than 0.05), whereas maximum R and maximum Tb were similar. After the additional 12-week conditioning, time on the treadmill increased 40% from 9.58 +/- 0.87 to 13.4 +/- 0.44 minutes, and maximum VO2 increased 27% to 48.1 +/- 9.1 ml/min/kg. These data indicated that maximum VO2 varied with intensity of the exercise, 12 weeks of maximal exercise conditioning was sufficient to produce a measurable training effect (ie, increase endurance and maximum oxygen consumption) and sheep are suitable for maximal exercise studies where VO2 measurements are desired.

Animals

Computer-controlled large-animal pulmonary function system.

Breath by breath determination of lung volume and specific lung conductance is challenging, yet desirable particularly when rapid changes in lung function accompany abrupt changes in lung volume. We have developed a large-animal pulmonary function data acquisition system using two personal computers with custom-made software which continuously tracks breath by breath changes in pulmonary function and lung volume. Accurate measurement of respiratory flow signals is accomplished by collecting separate pneumotachometer-derived expiratory and inspiratory flow signals, correcting them to standard temperature pressure dry (STPD) and summing them into a single flow data array. Calibration of inspiratory and expiratory flow is software corrected by comparison of the integrated flow signals with a sinusoidal pump system. Data are collected continuously for up to 120 min at 100 Hz/channel. Subroutines which configure the system to perform functional residual capacity, dosimetry and partial expiratory flow-volume maneuvers are user selected at any time during data collection.

Animals

Middle ear injury in animals exposed to complex blast waves inside an armored vehicle.

With greater reliance on armored vehicles of improved survivability, questions have arisen about the likelihood of the wounding of vehicle occupants from blast waves alone. In this study, we placed anesthetized animals (sheep or pigs) inside lightly armored vehicles and exposed them to the blast waves generated by one of three sizes of shaped-charge munitions. Sixty-seven animals were exposed and 15 served as controls. No difference was noted between exposed and control groups for blast injury to the respiratory or gastrointestinal tracts. In contrast, middle ear damage was observed exclusively in animals exposed to blast and was correlated strongly with the peak pressure. The ear is the organ most sensitive to blast damage, and if protectors are not used, military physicians can expect to see a high incidence of middle ear injury in modern combat. The operational consequences of such an injury are not known.

Animals

A steady state method of measuring carbon monoxide diffusing capacity of the lung of sheep.

A method for measuring the diffusing capacity of the lung for carbon monoxide (DLCO) in sheep was developed. The test's usefulness and reliability was studied in ten, splenectomized adult ewes. Hemoglobin concentration and weight were found to affect sheep DLCO. This article describes a method of determining DLCO in sheep, gives preliminary results of limited testing, and discusses factors affecting DLCO in sheep.

Animals

Cloth ballistic vest alters response to blast.

Ballistic wounds have been and will remain the principal cause of casualties in combat. Cloth ballistic vests (CBV) play an important role in limiting critical wounds from fragments and small-arms fire. There is an increased risk of primary blast injury on the modern battlefield. In a previous study, volunteers were exposed to short-duration blast waves of low peak pressure (18.6 +/- 0.8 kPa). Pressure measurements made in the distal esophagus as an estimate of intrathoracic pressure (ITP) were significantly higher (p less than 0.05) when the standard U.S. Army ballistic jacket was worn (8.7 +/- 1.2 kPa) than when fatigues alone were worn (7.4 +/- 0.7 kPa). In this study 58 sheep were exposed to nominal blast levels of 115, 230, 295, and 420 kPa peak pressure in groups of 12, 18, 16, and 12, respectively. Half of each group was fitted with a CBV. Lung weight index (LWI), lung weight expressed as a percentage of body weight, was used as a measure of blast injury. Use of the CBV was associated with a significant increase in LWI (p less than 0.05) which averaged 21% for the two middle exposure groups. At the 420 kPa level, two of six non-CBV animals died as opposed to five of six animals wearing the CBV. Intrathoracic pressure was generally higher in the CBV group. Likely mechanisms of injury enhancement include an increase in target surface area and an alteration of the effective loading function on the thorax. This information may be useful in the triage and treatment of casualties exposed to intense blast environments.

Animals

Effect of exercise in sheep on the absorption of intramuscular atropine sulfate.

In normal female sheep, we investigated effects of exercise on the absorption of atropine sulfate (0.02 mg/kg) given intramuscularly. The exercise regime consisted of treadmill running (20 min at 3-4 mph at 0 degrees grade) starting immediately after intramuscular atropine injection into the biceps femoris. Six normal female sheep received intramuscular atropine and 7-14 days later an identical intramuscular dose of atropine with exercise. Serum levels of atropine measured by radioimmunoassay were monitored over a 6-hour period. The time to peak concentration was significantly less with exercise than without, 2.9 +/- 2.1 and 13.7 +/- 5.4 min, respectively (p less than 0.005). In addition, peak serum atropine concentrations tended to be higher, 9.7 +/- 1.3 ng/ml with exercise versus 7.1 +/- 2.9 ng/ml without exercise; however, the difference did not attain statistical significance (p less than 0.08). This study demonstrates that exercise increases the early absorption of intramuscularly administered atropine sulfate.

Absorption

Etiopathogenic mechanisms of bronchoconstriction in byssinois--a review.

Studies of etiopathogenic mechanisms of bronchoconstriction in byssinosis indicate the possible involvement of histamine, 5-HT, platelet-activating factor, and metabolites of arachidonic acid as mediators of bronchoconstriction. These substances might be released by a variety of lung and/or recruited cells to induce construction of respiratory airways characteristic of the acute byssinotic reaction. It certainly seems possible that cotton dust induces acute bronchoconstriction by more than one mechanism and that a number of factors, both endogenous and exogenous, influence the increased bronchomotor response to cotton dust inhalation in any given textile worker.

Airway Resistance