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Biomedical subjects

L D Traber

Publications and source records attributed to L D Traber.

At least 109 records · Page 6Linked to original sources

[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)

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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.

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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.

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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.

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Pulmonary microvascular changes following fluid resuscitation in an ovine model of endotoxemia.

Fluid resuscitation is complicated in hypotensive septic patients by their susceptibility to pulmonary edema. This problem was evaluated in the ovine model of endotoxemia with a chronic lung lymph fistula. Escherichia coli endotoxin (lipopolysaccharide, 1.5 micrograms/kg) was given intravenously over 30 minutes. Group M (n = 9) continued to receive baseline fluids (2 mL/kg/h), while group R (n = 6) received 7 mL/kg/h of Ringer's lactate. After an initial drop in cardiac index, animals in both groups developed a hyperdynamic state. The fall in mean arterial pressure seen in group M was absent from group R. The higher fluid volume resulted in a rise in left atrial pressure and pulmonary microvascular pressure. The lung lymph flow and permeability index were elevated in both groups but were higher in group R. The calculated filtration coefficient showed a threefold increase in both groups. Augmented fluid resuscitation during endotoxemia resulted in an elevated interstitial fluid flux and permeability index secondary to an increase in pulmonary microvascular pressure and greater surface area of the injured microvascular beds being perfused.

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Early effects of inhalation injury on lung mechanics and pulmonary perfusion.

We investigated the early effects of a rather large amount of cotton-smoke on lung mechanics and pulmonary perfusion. Under halothane anesthesia 18 ewes were intubated with a double-lumen tube. In 6 sheep the left lung was exposed to smoke, in another 6 the right lung. A sham group of 6 sheep was insufflated with air instead of smoke. Prior to and 30-45 min following the smoking- (sham-) procedure the following parameters were determined for the smoke- (sham-) exposed and the contralateral lung: static compliance, inspiratory airway resistance, and physiologic dead space ratio. In addition MAP, MPAP, WP, and CO were recorded. The data indicate that inhalation of large amounts of smoke has no major direct effects on pulmonary mechanics and perfusion in the early post-injury period. Only an increase in airway resistance of the smoke exposed lungs was found, which must be attributed to a local reflex mechanism.

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Effect of antibody-mediated neutropenia on the cardiopulmonary response to endotoxemia.

An ovine anti-neutrophil antibody has been produced by immunizing rabbits with purified sheep neutrophils. Serial intraarterial infusions of anti-neutrophil antibody in awake instrumented sheep produced selective and profound neutropenia. Intravascular infusion of endotoxin (Escherichia coli, 1.5 micrograms/kg/30 min) resulted in significant and equivalent increases in pulmonary artery pressure, peripheral vascular resistance, and protein-rich pulmonary lymph flow in an endotoxin group (n = 9) and a depletion + endotoxin group (n = 4). Changes in cardiopulmonary parameters were most pronounced 2 to 8 hr after endotoxin administration in both groups. Cardiac index (CI) showed a precipitous and transient fall in both experimental groups at 0.5 to 1 hr after endotoxin infusion; however, by 8 hr CI rose significantly in the endotoxin group, while it remained unchanged in the depletion + endotoxin group. A significant rise in the peripheral neutrophil count was associated with the increase in CI in the endotoxin group. Plasma and pulmonary lymph levels of thromboxane-B2 were unchanged during the depletion period with a significant increase 1 hr after endotoxin infusion. In this study questions arise regarding the exclusive role of circulating neutrophils in the microvascular permeability changes seen in sepsis-mediated adult respiratory distress syndrome.

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Inhalation injury in burned patients: effects and treatment.

Pulmonary pathology in major thermal injury is found in 30-80 per cent of burn fatalities. The incidence and mortality from inhalation injury increases both with age and increasing burn size. Toxic smoke inhalation injury, characterized by increased lung microvascular permeability, is attenuated by increasing cardiac output to normal levels, indicating that fluid restriction after inhalation injury may lead to excessive lung fluid formation and hypoxia. Fluid administration of approximately 2 ml/kg/% area burned above the calculated resuscitation volume is required following an inhalation injury to provide adequate support for the systemic circulation and maintain cardiac output at normal levels. This additional volume does not contribute to the development of pulmonary oedema, but may decrease its formation by increasing shear forces thus reducing polymorphonuclear leucocyte deposition in the pulmonary microcirculation. Nasotracheal intubation is preferred when airway integrity is compromised by inhalation injury. The advantages are non-operative placement, ease of discontinuation, minimal bacterial contamination and leaving neck burns undisturbed. The administration of the appropriate antibiotics for documented infection is recommended, while steroids have been shown to be of no benefit.

Adolescent↗

Cardiopulmonary responses to continuous administration of endotoxin.

The cardiopulmonary response to continuous administration of lipopolysaccharide (LPS) was studied in chronically instrumented sheep. LPS was administered in doses of 0 (sham), 6, 9, 12, and 24 ng.kg-1.h-1 for 24 h. No significant changes in the measured variables occurred in the sham group and in the 6 ng.kg-1.h-1-LPS group. With 9, 12, and 24 ng.kg-1.h-1-LPS, cardiac index rose and peripheral resistance fell to the same extent in all three groups. Lung lymph flow (QL) increased with increasing concentration of LPS. These elevations in QL occurred in the presence of only minor increases in the pulmonary artery pressure, which rose to the same extent in the 9, 12, and 24 ng.kg-1.h-1 groups. Consequently, the changes in QL were attributable to changes in fluid conductance of the pulmonary microvasculature rather than variations in hydrostatic pressure. The increase in QL correlated with a decrease in prekallikrein levels (r = 0.97), indicating that the changes in fluid conductance might have been kinin mediated.

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Immunoreactive atrial natriuretic factor is increased in ovine model of endotoxemia.

A bolus of Escherichia coli endotoxin (1.5 micrograms/kg) was administered to chronically instrumented sheep. Immunoreactive atrial natriuretic factor (IR-ANF) was measured in extracted plasma by radioimmunoassay. There was a thirteenfold increase in IR-ANF 2 h after endotoxin administration, and IR-ANF levels remained significantly elevated during the first 6 h. A marked diuresis and natriuresis occurred between 4 and 6 h. ANF not only affects renal function but is also associated with decreased cardiac output, increased peripheral resistance (in sheep), and decreased capillary absorption (in rats). These renal and hemodynamic changes are also characteristic of the early (first 6 h) response to endotoxin. Therefore ANF should be considered as a potential mediator of renal and hemodynamic changes induced by sepsis. It is difficult to determine if ANF elevation is an epiphenomenon or a causative factor, because no antagonist of ANF is currently available.

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Increasing duration of smoke exposure induces more severe lung injury in sheep.

Eighteen sheep previously prepared for chronic study were divided into three groups of six animals each. These were given graded inhalation injury utilizing smoke obtained from burning cotton-toweling material. Smoke was insufflated into animals with a modified bee smoker at temperatures less than 40 degrees C. Group H, which received 64 breaths of smoke, showed the most pronounced changes in pulmonary function. The changes consisted mainly of a profound increase in lung lymph flow following a reduced P/F ratio (PO2 in arterial blood/inspired O2 fraction) and an elevation in both thermal and gravimetrically measured extravascular lung water. Similar changes were seen in group M (48 breaths of smoke) and group L (32 breaths of smoke). However, the injury was graded based on the changes in gravimetrically measured lung water and lung lymph flow. These were highest in group H and lowest in group L. These studies confirm our ability to accurately quantitate the injury induced by smoke inhalation. In addition, it demonstrates that lung injury associated with the inhalation of smoke can be graded depending on the duration of exposure.

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Treatment of smoke-induced pulmonary injury with nebulized dimethylsulfoxide.

Inhalation injury was produced in sheep that were chronically prepared for study. The injury was induced by insufflating them with smoke from burning cotton cloth. One group of animals was treated with the oxygen-free radical scavenger dimethylsulfoxide (DMSO) and heparin. Another group received heparin treatment alone, and a third was untreated. The drugs were nebulized into the tracheostomy at 4-hr intervals beginning 1 hr after injury. Following the inhalation injury, lung lymph flow and extravascular lung water measured by thermal-dye dilution technique were both increased. These elevations were associated with minor increases in pulmonary artery pressure, and, thus, since the lymph to plasma protein ratio was unchanged, this increased extravascular fluid formation was probably the result of an elevated microvascular permeability. These changes were associated with a reduction in alpha 2 macroglobulin antiprotease activity. The treated groups showed much smaller responses to the inhalation insult. This was especially true in the animals that received the DMSO. These findings support the concept that oxygen free radicals are responsible for the pulmonary edema associated with inhalation injury.

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Reduction of the cardiopulmonary response to endotoxin by the administration of aprotinin.

The antiprotease aprotinin (Trasylol) (20,000 KIU bolus/kg followed by 10,000 KIU/(kg x h) for 8 h) was administered to sheep which were then given a continuous dose of endotoxin (24 ng/(kg x h) for 24 h). Their cardiopulmonary response was compared to a group of sheep which received endotoxin alone as well as a sham group which received neither endotoxin nor aprotinin. The response to endotoxin was characterized by an increased lung lymph flow and cardiac output. This response was blocked by the administration of aprotinin. In the endotoxin group there was a fall in prekallikrein levels. The action of aprotinin suggests that the cardiopulmonary response to endotoxin may be mediated by the formation of bradykinin.

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The elastase-inhibitor eglin has no effect in an ovine model of endotoxemia.

Small doses of endotoxin have been shown to induce pulmonary microvascular injury in sheep, possibly by the action of granulocytes. Eglin, a potent inhibitor of neutrophil elastase, was tested in an ovine model of endotoxemia. The experiment was performed in 12 unanesthetized chronically instrumented sheep with a lung lymph preparation. Endotoxin (S. abort. equii) was infused at 24 ng/(kg x h) with application of 20 mg/kg eglin 1 h before endotoxin in the treatment group and followed by 5 mg/(kg x h). No significant improvement due to the treatment was seen for either cardiovascular status (pulmonary and systemic vascular resistance) or permeability changes in the lung (lymph flow and lymph/plasma protein ratio), although sufficient eglin concentrations were achieved in plasma and lymph. The lack of an effect of eglin might be because higher concentrations are needed to block elastase-like activity of ovine granulocytes or because of a minor role for neutrophil elastase in this shock model.

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