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Biomedical subjects

D L Traber

Publications and source records attributed to D L Traber.

At least 163 records · Page 9Linked to original sources
PubMed1990

Administration of a synthetic antiprotease reduces smoke-induced lung injury.

Our previous studies suggest that a neutrophil-mediated inflammatory injury causes a major fraction of the pulmonary edema that occurs after smoke inhalation. Because activated neutrophils extrude cytotoxic proteases, the current study was conducted to evaluate the role of proteases in the pulmonary microvascular injury. Twelve sheep, instrumented for collection of lung lymph, were insufflated with cotton smoke. The sheep were treated 30 min after smoke inhalation with either gabexate mesilate (an inhibitor of serine proteases) or vehicle. Smoke inhalation resulted in an increased protease activity in the lung interstitium, as evidenced by decreases in both antiprotease activity and immunoreactive alpha 2-macroglobulin. Intravenous infusion of gabexate mesilate prevented the decrease in antiprotease activity. The protease inhibitor significantly attenuated the smoke-induced increase in transvascular fluid and protein flux, with untreated animals exhibiting 460% increases in flux compared with 180% in the inhibitor treated sheep. The protease inhibitor also eliminated the functional degradation in gas exchange that was observed in the untreated sheep. These studies strongly suggest that an increase in pulmonary proteolytic enzyme activity is responsible for a significant fraction of the degradation in microvascular integrity and gas exchange that is associated with smoke inhalation injury.

Animals↗
PubMed1990

Intrapulmonary distribution of bronchial blood flow after moderate smoke inhalation.

The systemic blood flow to the airways of the left lung was determined by the radioactive microsphere technique before and 17 h after smoke inhalation in six conscious sheep (smoke group) and six sheep insufflated with air alone (sham group). Smoke inhalation caused a sixfold increase in systemic blood flow to the lower trachea (baseline 10.6 +/- 1.7 vs. injury 60.9 +/- 16.1 ml.min-1.100 g-1) and an 11- to 14-fold increase to the intrapulmonary central airways (baseline range 9.5 +/- 1.9 to 13.5 +/- 3.7 ml.min-1.100 g-1 vs. injury 104.6 +/- 32.2 to 187.3 +/- 83.6 ml.min-1.100 g-1). There was a trend for this hyperemic response to be greater as airway diameter decreased from the trachea to 2-mm-diam central airways. In airways smaller than 2 mm, the hyperemic response appeared to diminish. The total systemic blood flow to whole lung is predominantly to small peripheral airways and showed no significant increase from its baseline level of 17.5 +/- 3.7 ml.min-1.100 g-1 in the lung homogenate. Occlusion of the bronchoesophageal artery decreased central airway blood flow 60-80% and peripheral airway blood flow 40-60% in both the sham and the smoke groups.

Animals↗
PubMed1990

Determination of pulmonary microvascular reflection coefficient in sheep by venous occlusion.

We devised a technique that permitted elevation of pulmonary pressures in unanesthetized sheep by occluding their pulmonary veins. Using this technique, we raised pulmonary capillary pressure from a baseline of 13.2 +/- 2.2 to 35.3 +/- 5.1 mmHg. This increased lung lymph flow (from 8.8 +/- 2.7 to 53.1 +/- 13.9 ml/h). We estimated the pulmonary microvascular oncotic reflection coefficient and found it to be 0.82 +/- 0.05 (SD). The filtration coefficient was 0.019 +/- 0.005 ml.mmHg-1.min-1. During the period of increased pressure, the animals had stable arterial pressures and cardiac outputs. None of the animals developed blood coagulation problems. These data illustrate the usefulness of pulmonary venous occlusion to elevate pulmonary microvascular pressure to obtain plasma-to-lymph protein concentration ratios independent of flow, allowing for the calculation of the oncotic reflection coefficient.

Animals↗
PubMed1990

Impact of carbon monoxide on cardiopulmonary dysfunction after smoke inhalation injury.

With the inhalation of smoke, there are both cardiopulmonary changes and elevated levels of carbon monoxide (CO). We hypothesize that these changes in cardiopulmonary function are the result of a histotoxic hypoxia associated with CO poisoning. This hypothesis was tested in chronically instrumented sheep (n = 19). Piezoelectric crystals were attached to the left ventricle for the measurement of its external minor and major diameters in addition to wall thickness. A pressure transducer was placed in the left ventricle via the apex. The caudal-mediastinal lymph node was also cannulated. After a five-day recovery period, six sheep (smoke group) were insufflated with four series of 16 breaths (700 ml/breath) of cotton smoke, and five sheep (control group) were insufflated with air using a modified bee smoker (smoke group: COHb, 90 +/- 6%; control group: COHb, 6 +/- 1%). Eight sheep (CO group) were ventilated with 2% CO in air to reach a COHb of 90% (COHb, 92 +/- 1%). In the smoke group, lung lymph flow reached 42 +/- 10 ml/hr at 24 hours after smoke insufflation (baseline, 6 +/- 1 ml/hr). The maximum elastance of the left ventricle (end-systolic pressure-volume ratio), a sensitive index of myocardial contractility, was significantly decreased from a baseline of 6.5 +/- 0.9 to 3.3 +/- 0.7 mm Hg/ml. In the control and CO group, neither lung lymph flow nor maximum elastance varied from the baseline value. We conclude that the cardiopulmonary dysfunction after smoke inhalation does not occur after a similar exposure to CO. Initial CO poisoning alone is not a causative factor of cardiopulmonary dysfunction after smoke inhalation.

Animals↗
PubMed1990

Inhalation injury to tracheal epithelium in an ovine model of cotton smoke exposure. Early phase (30 minutes).

The purpose of this study was to evaluate lung cell injury during the acute phase of smoke inhalation injury. A group of 10 sheep were anesthetized with halothane and pancuronium followed by endotracheal intubation. In the first experiment 5 sheep were given air (sham group) and 5 were insufflated with cooled cotton smoke with a modified bee smoker. In the second part of our study (Experiment 2) the animals were insufflated with the following number of smoke breaths: 1 x 12 (n = 3); 2 x 12 (n = 4); 3 x 12 (n = 4) 4 x 12 (n = 4); and sham control (n = 1). After 30 min the animals were killed with KCl and the trachea prepared for scanning, transmission electron, and light microscopy. Our initial observation with scanning electron microscopy revealed a large amount of mucus on the surface of the epithelia. Numerous ciliated cells had been sloughed from the epithelium and were observed on the surface of the remaining ciliated cells. The sloughed cells were intact, and the cilia remained on the apical cell surface. Light and transmission electron microscopy revealed that most goblet cells were in the process of extruding mucus. The cytoplasm of goblet and basal cells appeared normal. Ciliated cells had a slightly vesiculated cytoplasm, and many were in the process of being sloughed from the epithelial surface. In these cells desmosomal attachment had been separated. The light microscope evaluation of the tracheal epithelium showed there was no dose-dependent effect between the four treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Does heparin improve survival in experimental porcine gram-negative septic shock?

To evaluate the effects of heparin on gram-negative septic shock, immature piglets were subjected to fecal Escherichia coli peritonitis. One group of animals received a continuous infusion of heparin 25 units/kg/hr, while the control animals were given an equivalent volume of lactated Ringer's solution. Heparin-treated animals (n = 5) had a mean survival time (+/- SEM) of 18.8 +/- 2.2 hr vs. 11.9 +/- 2.8 (P less than 0.05) in controls (n = 5). Animals receiving heparin tended to have improved hemodynamic profiles and less leukopenia than controls.

Animals↗
PubMed1990

Airway aspiration of hydrochloric acid in sheep.

We have compared the effects of aspiration of 2.5 ml/kg of 0.1 N hydrochloric acid (HCl) on groups undergoing normal saline aspiration (2.5 ml/kg) and a sham control in unanesthetized sheep with chronic lung lymph fistula for up to 148 hr. Significant changes in pulmonary lymph flow and cardiopulmonary variables occurred in the airway acid group within the first 48 hr, as compared to saline and sham control. In the HCl group lymph flow increased from a baseline of 8.5 +/- 1.5 to 21.8 +/- 3.0 ml/hr (mean +/- SEM) at 2 hr. Pulmonary vasoconstriction occurred at this time with significant elevations of lymph thromboxane B2 from a baseline of 400 +/- 11 to 2,090 +/- 690 pg/ml. During the early acid aspiration phase products of lipid peroxidation were noted to increase from 0.29 +/- 0.03 to 0.81 +/- 0.17 absorbance units. Associated with elevated lymph flow was a significant drop in cardiac index in the airway-acid-aspirated group (6.59 +/- 0.52 to 5.53 +/- 0.36 L/min/m2) and a rise in bronchial blood flow from 9.8 +/- 1.7 to 63.7 +/- 8.9 ml/min. These data suggest that a moderate airway acid injury created by 2.5 ml/kg of HCl results in acute pulmonary damage with the release of several potential mediators which may be responsible for the observed effects. The long-term acid-injured animals survived for up to 1 week following the aspiration procedure with evidence of resolution of lung damage by wet-weight dry-weight evaluation of lung (normal lab control = 4.0 +/- 0.2, and 148 hr after acid = 4.5 +/- 0.3) and microscopic evidence of minimal persistent injury. These data document the pulmonary damage and repair resulting from airway acid instillation.

Animals↗
PubMed1989

Pulmonary deposition and clearance of aerosolized alpha-1-proteinase inhibitor administered to dogs and to sheep.

Augmentation of lung antiprotease levels may be an important therapeutic intervention in the prevention of pulmonary emphysema. We have administered aerosols of plasma-derived human alpha 1 proteinase inhibitor (A1PI) to the lungs of dogs and sheep to investigate (a) delivery of the protein to the distal air spaces of the lung; (b) maintenance of functional activity of the protein; and (c) flux of the protein across the components of the alveolar-capillary membrane. A1PI (26.4 mg/kg body weight) was administered as an aerosol to anesthetized animals; sheep were prepared for the chronic collection of lung lymph. Immunoperoxidase staining of lung tissue obtained 2 h after administration of A1PI demonstrated the presence of human A1PI on the surface of alveoli and distal bronchioles. Bronchoalveolar lavage fluid recovered at intervals after A1PI administration demonstrated time-dependent elevations of human A1PI levels with augmentation of lavage fluid antielastase activity in proportion to the content of human A1PI. Using radiolabeled A1PI as a tracer, we found that 32% of the aerosol was retained in the animals' lungs. Measurements of the rate of loss of A1PI from the lung and of the rate of appearance of human A1PI in plasma resulted in a calculated permeability of the alveolar-capillary membrane to A1PI of 3.49-6.39 X 10(-10) cm/s. Experiments using instrumented sheep allowed independent calculation of endothelial permeability to A1PI of 122-236 X 10(-10) cm/s and calculation of epithelial permeability of 4.70-4.81 X 10(-10) cm/s. Modeling of aerosol delivery of A1PI to humans using the results of these studies predicts that the ratio of plasma/alveolar levels of delivered A1PI will be 0.024, and that aerosolization of 175 mg A1PI/d will result in an A1PI alveolar fluid level of 1.0 mg/ml. Aerosol administration of A1PI may provide an efficient method of augmenting alveolar antiprotease levels.

Aerosols↗
PubMed1989

[Respiratory and hemodynamic sequelae of unilateral inhalation injury of the lung].

Respiratory failure after smoke inhalation injury is usually preceded by a 12-48 h interval with only minor clinical symptoms. Since pulmonary lesions show a patchy distribution, it has been postulated that vasoconstriction in more severely damaged areas induces a shift of pulmonary blood flow to less severely damaged areas, minimizing venous admixture. This hypothesis was tested in a sheep model in which only one lung was exposed to smoke. Six chronically instrumented (arterial, central venous, pulmonary artery thermodilution, and left atrial catheters; ultrasonic transit time flow probe around the left pulmonary artery) range ewes were intubated with a modified Carlens tube under halothane anesthesia. Smoke from smoldering cotton was insufflated into the left lung until a carboxyhemoglobin level of 50% was achieved. After the smoking procedure, the animals were awakened, extubated, and studied for 24 h. During this time, the pulmonary vascular resistance of the left lungs increased fourfold while the pulmonary vascular resistance of both lungs only doubled. Left pulmonary artery blood flow decreased progressively to 37% of control at 24 h, while cardiac output decreased by only 25%. PaO2 decreased from 107 +/- 12 to 77 +/- 15 mmHg at 24 h. Mean pulmonary arterial pressure rose from 18 to 23 mmHg. Heart rate, mean arterial pressure, left atrial pressure, and PaCO2 showed no statistically significant changes. The results indicate that the response of the pulmonary vasculature to smoke inhalation injury is a two-phase phenomenon. In the first phase, vasoconstriction occurs to counterbalance injury-induced ventilation-perfusion mismatching.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Cardiopulmonary changes occurring with pulmonary intravascular clearance of live bacteria in sheep.

Sheep were infused with live bacteria to determine if the bacteria are phagocytized in the pulmonary circulation and to study the associated cardiopulmonary changes. Unanesthetized animals (n = 9) with chronic hemodynamic and pulmonary lymph catheters received a 1 hr central venous infusion of live Pseudomonas aeruginosa (5 x 10(7) Ps./minute) and were compared to a sham group (n = 7). The pulmonary arterial levels of bacteria were five to 100 times higher than the aortic levels. Pulmonary intravascular clearance rates were 79-91%. Electron microscopy of the lungs 24 hr after the bacterial infusion showed that pulmonary intravascular macrophages and neutrophils phagocytosed the bacteria. Severe initial and mild persistent pulmonary hypertension occurred. The pulmonary lymph flow was elevated, initially from hydrostatic pressure and later from increased permeability. A hyperdynamic circulation occurred from 6 to 18 hr, with elevated cardiac index and lowered systemic vascular resistance and mean arterial pressure, mimicking cardiopulmonary changes seen in clinical sepsis. The removal of bacteria in the lungs may contribute to the injury in sheep.

Animals↗
PubMed1989

Comparison of the cardiopulmonary responses to single bolus and continuous infusion of endotoxin in an ovine model.

We compared the cardiopulmonary responses to a single bolus (1.5 microgram/kg) vs. continuous infusion of endotoxin (LPS) (24 ng/kg/hr) in unanesthetized sheep. A single bolus produced an initial marked increase in pulmonary arterial pressure and plasma thromboxane levels and an elevated flow rate of lung lymph low in protein. Concomitantly, the cardiac output dropped and systemic vascular resistance rose. In the animals that received a continuous infusion of LPS, only very small changes in these variables were noted during this early period. Later, lung lymph flow rate and protein flux were elevated in both groups with a greater response in the bolus group. At 6 hr after LPS, the systemic vascular resistance fell in both groups, but to a greater extent in the bolus group, whereas the cardiac output rose to the same extent. Plasma levels of neutrophils, lymphocytes, and plasma prekallikrein levels decreased in both groups; neutropenia was more pronounced in the bolus group. The most important difference between both endotoxemia models during this phase was the reduction of the stroke work index in the bolus model, which was not observed with the continuous infusion. The apparent myocardial depression, the early reduction in cardiac output, and eicosanoid mediated pulmonary hypertension are the major differences between the two responses.

Animals↗
PubMed1989

Cardiovascular reaction pattern during endotoxin or peptidoglycan application in awake sheep.

Peptidoglycans (PG) and lipopolysaccharides (LPS) are cell wall constituents of bacteria. The relative contents vary significantly between gram-negative and gram-positive strains. Since both strains take part in clinical septicemia, we compared hemodynamic and permeability properties in a sheep model with chronic instrumentation and lung lymph drainage. The cardiovascular reaction patterns of PG and LPS were comparable at very different dose levels, with LPS being 10,000-fold more potent. Continuous infusion produced an increase in lung permeability (only with LPS) and cardiac output, as well as fever, to mimic the hyperdynamic situation in early septicemia.

Animals↗
PubMed1989

Morphological studies on the venous drainage of the trachea in the neck of sheep.

Systemic venous drainage of the cervical portion of the trachea from the cricoid cartilage to the sternal notch was observed in 50 adult sheep. In all animals, the first five to six tracheal rings starting at the cricoid cartilage were drained by the thyroid veins (v. thyroideae) bilaterally to the external jugular veins (v. jugularis externa). A venous complex draining the remaining cervical portion of the trachea was observed only on the left side of the trachea. This complex drained to the cranial vena cava (vena cava cranialis). India ink or Evans blue dye were infused into small vessels draining this area for verification. Variations in this venous complex were classified into three types based upon length of trachea drained. Type I was found in 26%, type II found in 58%, and type III found in 16% of the sheep studied and drained 23 +/- 5%, 58 +/- 11% and 78 +/- 10% of the cervical portion of the trachea, respectively. Blood flow from this area of the trachea was 85 +/- 28 mL/min/100 g wet issue. This study identified and classified the venous drainage of the cervical portion of the trachea in sheep.

Animals↗