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Biomedical subjects

L D Traber

Publications and source records attributed to L D Traber.

141 records · Page 8Linked to original sources
PubMedDate not supplied

Effects of an L-selectin antibody on the pulmonary and systemic manifestations of severe smoke inhalation injuries in sheep.

Sheep were treated with either lymphocyte adhesion molecule (LAM)1-3, an antibody against L-selectin, (40 mg 1 hour before smoke inhalation and 35 mg 24 hours after smoke inhalation; n = 6) or equivalent volumes of 0.9% saline solution (n = 6). After the smoke inhalation injuries, the PaO2/FIO2 ratio declined in both groups until 40 hours after the injuries, when a trend toward improvement was noted in the group that received LAM1-3. Lung lymph flow increased in both groups until 36 hours after the smoke inhalation injuries and then significantly decreased in the group that received LAM1-3. Forty-eight hours after the smoke inhalation injuries, there was a significant decrease in the ratio of wet-dry lung weight and in preservation of the reflection coefficient in the group that received LAM1-3 (P < .05). Histopathologic examination showed no differences between the groups in the pulmonary morphology associated with smoke inhalation. A reduction in splanchnic blood flow was noted in the control group (P < .05); this reduction was attenuated by treatment with LAM1-3. The delayed pulmonary effects and improved splanchnic blood flow suggested that LAM1-3 attenuated the development of a systemically induced secondary lung injury rather than of the primary lung injury associated with smoke inhalation.

Animals↗
PubMedDate not supplied

Dimethylsulfoxide with heparin in the treatment of smoke inhalation injury.

Recent studies suggest that lung lesions occurring in inhalation injury result from actions of oxygen-free radicals released from polymorphonuclear leukocytes marginating in the pulmonary microcirculation and tracheobronchial region. Peroxide and hydroxyl ions have been implicated as mediators in the increased microvascular permeability and pulmonary edema noted after inhalation injury. In this study we evaluated the use of an O2-free radical scavenger, dimethylsulfoxide (DMSO), and heparin in the treatment of smoke inhalation. Ewes (N = 26) that had been surgically prepared five days earlier were insufflated with smoke from burning cotton. There were four groups: controls (n = 7), DMSO (n = 6), heparin (n = 6), and DMSO plus heparin (n = 7). All animals were given ventilatory support to maintain their PO2 above 60 mmHg and their PCO2 below 45 mmHg. There was a significant difference in survival rates between groups. By 72 hours all seven of the control group were dead. All animals in the DMSO plus heparin group survived, four of the DMSO group died, and two of the heparin group died. Lung lymph flow was not as high in the DMSO plus heparin group as in the heparin-only group. DMSO was proved effective in reducing the lung injury associated with smoke inhalation.

Animals↗
PubMedDate not supplied

Lack of hematogenous mediated pulmonary injury with smoke inhalation.

Inhalation injury was studied in chronically prepared sheep (n = 12) by insufflating one lung with cotton smoke from burning cotton cloth. The contralateral lung was insufflated with air. There was also a sham group in which both lungs were insufflated with air (n = 6). The pulmonary status of the smoked animals gradually deteriorated; by 24 hours shunt blood flow had increased to 32 +/- 3% and the animals were sacrificed. Wet-weight/dry-weight ratios were elevated only in the smoke-exposed lungs. They likewise showed histologic evidence of injury. Lavage materials from the injured lungs had higher percentages of neutrophils than the others. The lung lesion produced by the inhalation of cotton smoke appears to be localized to the area of injury, rather than being a generalized pulmonary response.

Animals↗
PubMedDate not supplied

Effect of preexisting inhalation injury on response to bacteremia in sheep.

Inhalation injury increases the likelihood of sepsis. We tested the hypothesis that preexisting inhalation injury would diminish bacterial clearance across the pulmonary vasculature and induce greater hemodynamic response. Live Pseudomonas aeruginosa were infused centrally for one hour in three groups of awake sheep. Inh + Ps (n = 10), with a seven to 10-day-old inhalation injury; Ps-LOW (n = 8) both received 10(7) Ps/min; and Ps-HI (n = 9) received 5 x 10(7) Ps/min. for one hour. Pulmonary hypertension was more severe in Ps-HI and Inh + Ps. A hyperdynamic response with high cardiac index and low mean arterial pressure developed in Inh + Ps and Ps-HI from six to 18 hr, while Ps-LOW, only the cardiac index was elevated at six to eight hr. The Inh + Ps and Ps-LOW groups had equivalent pulmonary artery and aortic bacterial levels, while Ps-HI had levels approximately five times higher. All groups removed bacteria efficiently in the lungs. However, preexistent inhalation injury exaggerated the pulmonary and systemic hemodynamic response.

Animals↗
PubMedDate not supplied

The effect of thromboxane synthetase inhibition on cardiopulmonary function during endotoxemia in sheep.

The early pulmonary hypertension seen with endotoxin (lipopolysaccharide) has been reported as resulting from the release of thromboxane A2. We studied the cardiopulmonary response to endotoxin in sheep with and without treatment with a thromboxane synthetase inhibitor, OKY-046. The animals were implanted with instruments for crystallographic dimension analysis of the left ventricle and measurement of left ventricular, aortic, left atrial, and pulmonary arterial pressures and cardiac index. Thirteen sheep received 1.0 micrograms/kg of Escherichia coli endotoxin with (n = 6) and without (n = 7) OKY-046 (10 mg/kg bolus, then 10 micrograms/kg/min). OKY-046 prevented the increase in pulmonary arterial pressure and decrease in cardiac index usually seen during the early phase of endotoxemia. Between 8 and 12 hours after the administration of endotoxin, cardiac index increased from 6.4 +/- 0.8 to 8.4 +/- 0.8 L/min/m2. Concomitantly, the end-systolic pressure/diameter relationship (a sensitive myocardial contractility index) significantly decreased from 14.7 +/- 0.6 to 7.7 +/- 0.7 mm Hg/mm. Another index of the left ventricular contractility, the maximum rate of pressure rise was also reduced. OKY-046 prevented decreases in end-systolic pressure/diameter relationship and maximum rate of pressure rise.

Animals↗
PubMedDate not supplied

Endoscopic laser flowmetry: a valid method for detection and quantitative analysis of inhalation injury.

Hyperemia of the tracheobronchial area is a major sign of inhalation injury. However, this is usually a qualitative symptom, without quantitative measurement. We have developed a technique to diagnose inhalation injury and to analyze damaged areas quantitatively with laser-doppler flowmetry. In chronically instrumented sheep (N = 10), the tissue blood flow in the wall of second generation bronchi was determined with an endoscopic flowmeter probe. After baseline data had been obtained, the right lung was exposed to smoke in seven animals. Three sham-smoked animals underwent the same procedure, but without actual smoke. The bronchial blood flow was measured again 30 minutes after insufflation in both groups. Inhalation injury caused a significant increase in flow, from 35.1 +/- 2.6 to 51.7 +/- 2.1 ml/min.100 gm tissue in the airway of the smoked lungs but not in the control lungs. This increase correlated with an increase in the carboxyhemoglobin level (r = 0.87). The sham-smoked animals showed no change in bronchial blood flow. A valid technique for diagnosing inhalation injury in the early phase and a quantitative analysis of injured areas has been demonstrated.

Animals↗
PubMedDate not supplied

The effect of dopamine on pulmonary hemodynamics and tissue damage after inhalation injury in an ovine model.

Hypoxic pulmonary vasoconstriction and reduced blood flow occur as a result of smoke inhalation. The aim of this study was to investigate how the amelioration of blood flow reduction by the vasodilator dopamine affects histopathologic outcome. We exposed the left lungs of chronically instrumented sheep (n = 12) to smoke, awakened them, and studied them for 24 hours. Six hours after inhalation injury, the sheep received randomized infusions of dopamine (9 micrograms/kg/min) or equal volumes of 0.9% saline solution. Pulmonary resistance in the left lungs of animals in the group that received saline solution rose continuously throughout the study period (624 +/- 48 dyne.sec.cm-5/m2 to 1747 +/- 140 dyne.sec.cm-5/m2, baseline to 24 hours after injury). Dopamine treatment caused a significantly lower vascular resistance in the injured lung than did saline solution between 8 and 24 hours after injury. The histologic evaluation of the injured lungs showed epithelial necrosis and cast formation in both groups in addition to an increased wet/dry ratio. No difference in lung injury between the groups could be distinguished. We conclude that the amelioration of blood flow reduction by treatment with dopamine in the lungs that were exposed to smoke did not affect pulmonary damage after inhalation injury.

Animals↗
PubMedDate not supplied

Carbon monoxide and pulmonary circulation in an ovine model.

The direct pulmonary vasoconstrictive effects of inhaled carbon monoxide were evaluated in chronically instrumented and anesthetized sheep (1.7% halothane in air) (n = 8). The response to carbon monoxide (2%), which was applied for 8 minutes through a double-lumen tube alternately to the left or right lung of each animal, was compared with baseline values. The induced carboxyhemoglobin level (65%) led to increases in cardiac output, pulmonary arterial pressure, stroke volume index, and heart rate. Systemic vascular resistance decreased, and pulmonary vascular resistance and mean arterial pressure were unchanged. The changes in pressure and flow were equivalent no matter which lung was exposed to carbon monoxide. No diversion of blood from one lung to the other was observed during the test period. We conclude that carbon monoxide does not have a direct pulmonary vasoconstrictive effect. The increase in pulmonary arterial pressure is a result of the decrease in mixed venous oxygen content (stimulus for hypoxic pulmonary vasoconstriction) and the increase in cardiac output.

Animals↗
PubMedDate not supplied

Is the CD18 adhesion complex of polymorphonuclear leukocytes involved in smoke-induced lung damage? A morphometric study.

Neutrophils are the primary vectors that produce lung parenchymal injury after smoke inhalation as a result of their transmigration through endothelial and epithelial gap junctions toward the airway surfaces. LFA-1 (CD11a/CD18) on the neutrophil surface is essential for this transmigration in many tissues. We hypothesized that anti-CD18 antibodies would block such movement and prevent lung damage. Ten sheep received nebulized cotton smoke in our standardized model of inhalation injury. The sham group (n = 2) was insufflated with air only, the second group (n = 4) was insufflated with smoke but received no antibody, and the third group (n = 4) was given monoclonal antibody R15.7 before smoke injury. A similar degree of parenchymal injury and an alveolar epithelial reparative response were measured in both groups receiving injury. Neutrophil counts in the interstitium of both injured groups were also similar. However, in the R15.7 pretreated group, neutrophils remained inside the capillary in far larger numbers (p < 0.05). The CD11/18 adhesion complex may not be necessary for the pulmonary microvascular changes associated with inhalation injury.

Animals↗
PubMedDate not supplied

Plasma copper and iron changes in sheep after left lung inhalation injury: effect of the thromboxane antagonist BM 13.177 (Solutroban).

A significant decline in plasma concentrations of copper and iron were observed in sheep exposed to preferential smoke inhalation of the left lung. The decline was evident 30 minutes after smoke inhalation, and the levels of both trace metals persisted at quite low levels for up to the 18-hour time interval after injury. From that time a gradual recover for copper but not for iron levels was observed so that by 24 hours the levels of copper were in the same range of those at baseline. Copper and iron levels showed an inverse correlation to airway peak and plateau pressures and left lung vascular resistance index and a direct correlation to left lung blood flow. Administration of BM 13.177 (Solutroban), a thromboxane antagonist, before exposure to smoke inhalation protected the sheep from the decline of copper and iron levels in plasma. In these animals airway peak and plateau pressure, left lung vascular resistance, and blood flow were also unmodified. Lipid peroxidation of the lung tissue by oxygen free radicals were lower than in those animals that did not receive BM 13.177. There was likewise a tendency of a decreased wet-to-dry weight ratios in the animals treated with BM 13.177. BM 13.177 treatment in an inhalation injury model might partly protect lung damage and parallels unchanged plasma copper and iron levels. The plasma copper and iron may therefore be an indicator of acute lung damage.

Analysis of Variance↗
PubMedDate not supplied

Inhaled nitric oxide selectively reduces pulmonary hypertension after ovine smoke inhalation but does not improve oxygenation.

Inhaled nitric oxide (NO) is known to selectively reduce pulmonary hypertension and improve the ventilation-perfusion relationship in subjects with lung injury of various origin. However, some forms of lung injury do not react to inhaled NO at all, or show only a reduction in pulmonary arterial pressure. Very little is known about the effects of inhaled NO after smoke inhalation injury. We investigated the effects of inhaled NO in an established model of ovine smoke inhalation injury. Chronically instrumented sheep (n = 8) had tracheostomies and were insufflated with smoke generated from burning cotton cloth (4 times at 12 breaths each). They were then connected to a ventilator with oxygen-enriched air to achieve arterial oxygen tensions within the normal range. After 48 hours, NO was added to the inspired gas in ascending concentrations of up to 100 ppm. Systemic and pulmonary hemodynamics as well as oxygen transport were analyzed. Inhaled NO dose dependently lowered the pulmonary hypertension. Concentrations higher than 20 ppm did not further reduce the pulmonary artery pressure. Right ventricular stroke work index was significantly improved owing to the reduction in pulmonary vascular resistance. Arterial oxygenation, however, was not optimized by inhaled NO, probably because of interstitial edema formation.

Administration, Inhalation↗
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Enhanced pulmonary expression of endothelin-1 in an ovine model of smoke inhalation injury.

Recent studies suggest a role of endothelin-1 (ET-1) in mediating airway inflammation and lung injury. The aim of this study was to assess the immunohistochemical expression of ET-1 in the lung following smoke inhalation injury. ET-1 immunoreactivity was assessed in normal sheep (N = 4) and in sheep at 1 (N = 2), 6 (N = 3), 12 (N = 3), and 24 (N = 3) hours after inhalation injury. In normal animals, ET-1 expression was limited to the basal cell layer of the tracheal epithelium, main bronchi, and associated mucous glands. One hour after injury, ET-1 immunoreactivity was enhanced in upper airway epithelium and mucus glands with new expression in bronchioles. Airway smooth muscle, vascular tissue, and alveolar duct smooth muscle cells expressed moderate levels of ET-1 at 12 and 24 hours. ET-1 immunoreactivity was absent in areas of parenchymal edema and inflammation. The pattern of ET-1 expression following inhalation injury suggests that this peptide may contribute to the airway inflammation, mucus secretion, pulmonary hypertension, increased airway resistance, and decreased lung compliance, which are evident in our ovine model of inhalation injury.

Animals↗
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Use of an intravascular oxygenator/carbon dioxide removal device in an ovine smoke inhalation injury model.

The intravascular oxygenator/carbon dioxide removal device (IVOX) is a hollow fiber, implantable membrane oxygenator that lies in the vena cavae and is designed to augment gas exchange during acute respiratory failure. An ovine model of smoke inhalation injury (lethal dose for 50% of animals at 48 hr) was used in eight ewes to test the safety and efficacy of this device. The IVOX was placed in the vena cavae through a right internal jugular vein cut-down. A vacuum pump withdrew O2 through the hollow fiber membrane, and IVOX gas flow was measured with a flow meter. Outlet gas was analyzed for CO2 concentration. Changes in O2 exchange were calculated as changes in mixed venous O2 content with the IVOX on compared with the IVOX off, multiplied by the cardiac output. The IVOX did not significantly change cardiac output, mean arterial pressure, pulmonary artery pressure, or hemoglobin concentration measured every 6 hr for 48 hr. The maximum CO2 exchange averaged 40.2 +/- 10.5 ml CO2/min. The average change in oxygen exchange was 98.4 +/- 76.0 ml O2/min. Iliac vein injury from attempted IVOX placement without fluoroscopic guidance resulted in one death. The authors concluded that the IVOX was safe when properly inserted and provided approximately 25-30% of the gas exchange requirements in this model.

Animals↗