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Biomedical subjects

T G Mundie

Publications and source records attributed to T G Mundie.

16 recordsLinked to original sources

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

Byssinosis: Release of prostaglandins, thromboxane, and 5-hydroxytryptamine in bronchopulmonary lavage fluid after inhalation of cotton dust extracts.

New Zealand White rabbits were exposed intratracheally to aerosolized cotton dust extract (CDE) for 5 minutes of tidal breathing and lavaged 15 minutes 1, 4, and 6 hours after exposure. Bronchoalveolar lavage cells were counted, and the number of macrophages and polymorphonuclear leukocytes (PMNs) was determined. Cell recruitment, which began 1 hour after exposure to CDE and plateaued at 6 hours, consisted of both mononuclear cells and PMNs. Lavage fluid was analyzed for concentrations of prostaglandin F2 alpha (PGF2 alpha), prostaglandin E1 and E2 (PGE), thromboxane B2 (TxB2), and 5-hydroxytryptamine (5-HT). PGF2 alpha, PGE, TxB2, and 5-HT were maximally increased in the lavage 4 hours after exposure to CDE. This is the first study to demonstrate the in vivo release of arachidonic acid metabolites and 5-HT in the lung in response to CDE inhalation. This study also demonstrates that maximum mediator release occurs at 4 hours after exposure to aerosolized CDE. These findings strongly suggest that arachidonic acid metabolites are available to mediate either totally or partially the pathogenic mechanism(s) of bronchoconstriction seen in the acute byssinotic reaction of man.

Administration, Intranasal

Byssinosis: thromboxane release from human platelets by cotton dust and bract extracts.

Extracts of cotton dust and bract induced in vitro release of arachidonic acid metabolite thromboxane A2 (TxA2), a potent bronchoconstricting agent, from human platelets. TxA2 release, determined by radioimmunoassay of the stabile metabolite TxB2, was both time- and dose-dependent. Cotton green bract extract was significantly more potent in releasing TxA2 from human platelets than cotton dust extract or cotton brown bract (field-dried bract) extract, while brown bract extract was least active, which suggests that the etiological agent(s) is of plant origin and not microbial in nature. TxA2 release was shown to be enzyme-dependent by inhibition of the reaction by indomethacin (cyclooxygenase inhibitor) and 7-(1-imidazolyl) heptanoic acid (thromboxane synthetase inhibitor). This study is the first to show in vitro platelet TxA2 release by cotton extracts and may provide an explanation for increased concentrations of TxB2, a metabolite of TxA2, in the bronchoalveolar spaces of rabbits exposed to aerosolized cotton dust extract. Platelet aggregation and production of TxA2 may prove to be an important mechanism in the pathogenesis of bronchoconstriction in byssinosis.

Blood Platelets

Byssinosis: serum immunoglobulin and complement concentrations in cotton mill workers.

In two separate studies (labeled A and B), concentrations of IgC, IgM, IgA, C3, and C4 were determined in the sera of byssinotic and non-byssinotic cotton mill workers. In study A, sera were collected on Monday morning and Monday afternoon and Friday afternoon in order to ascertain if the waning byssinotic response from Monday to Friday correlates with changes in serum immunoglobulin and complement concentrations. In study B, sera was collected on Monday morning and afternoon and was performed primarily to evaluate history of atopy and smoking as complicating factors in byssinosis. In study A, the concentrations of all immunoproteins were found to decrease from Monday morning to to Friday afternoon in all textile workers, and in study B only C3 concentration decreased morning to afternoon. There was, however, no difference between the immunoprotein changes for byssinotic workers when compared to non-byssinotic workers in either study. Due to the fact that hypersensitivity pneumonitis causes a decrease in immunoprotein concentrations in affected workers while no decreases are noticed in normal workers, our data do not support an immune complex etiology for byssinosis. In addition, decreased serum C3 concentrations observed in this study could be caused by complement activation; however, there was no difference in complement levels between byssinotic and non-byssinotic textile workers. Therefore, these data neither support nor eliminate the involvement of antibody-independent complement activation in the pathogenesis of byssinosis.

Byssinosis