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Biomedical subjects

D L Traber

Publications and source records attributed to D L Traber.

At least 91 records · Page 5Linked to original sources
PubMed1996

Effect of severe smoke inhalation injury on systemic microvascular blood flow in sheep.

Multiple nonpulmonary organ dysfunction is frequently associated with acute lung injury; however, the mechanisms underlying the pathogenesis of this process are not completely understood. Decreased oxygen delivery to distant organs due to maldistribution of blood flow may be a contributing factor. We examined the effects of acute lung injury induced by smoke inhalation on microvascular blood flow to various organs in sheep. Seven sheep were prepared with arterial, venous, pulmonary artery, and left atrial catheters. After a 5 day recovery period, a tracheostomy was performed, followed by insufflation with 48 breaths of cool cotton smoke. Determination of microvascular blood flow using colored microspheres, standard hemodynamic measures, and blood gas analysis were performed before and at 12 h intervals after smoke inhalation. Animals were resuscitated to maintain left atrial pressure at +/- 2 mmHg of the baseline value and FiO2 was adjusted to maintain Sao2 at > 90%. After 48 h, sheep were killed and an autopsy was performed. Samples of trachea, left ventricle, ileum, colon, spleen, pancreas, and cortex from both kidneys were obtained for determination of microvascular blood flow. Blood flow to the trachea was substantially increased, while blood flow to the kidneys was preserved near baseline levels. Left ventricular blood flow decreased slightly; however, this decline was not statistically significant. Blood flow to ileum, colon, spleen, and pancreas was significantly decreased, particularly at 36 and 48 h after injury. These decreases were independent of changes in cardiac output or systemic oxygen delivery. It is likely that alteration in microvascular blood flow may contribute to the development of nonpulmonary organ dysfunction after acute lung injury.

Animals↗
PubMed1995

Effects of ibuprofen on airway vascular response to cotton smoke injury.

We studied the effects of ibuprofen on bronchial blood flow and myocardial function after inhalation injury. Sheep (n = 12) were chronically instrumented with cardiovascular and pulmonary catheters. After 5 days of recovery period, baseline data were collected and the sheep were divided into two groups. Group S (n = 6) were insufflated with 48 breaths of cotton smoke; while group I (n = 6) were pretreated with ibuprofen (12mg/kg bolus followed by 3 mg/kg/h continuous infusion for 24 h) and challenged with the same dose of smoke. All the animals were studied for 24h. Bronchial blood flow increased significantly in both groups throughout the experimental period; while stroke volume as well as right and left ventricular stroke work indices of both groups were significantly decreased (group I worse than group S) in the second half of the experimental period. These data suggest that vasodilatory prostaglandins do not play a major role in the bronchial vascular response to smoke inhalation injury and myocardial depression seen post injury is worse in animals treated with ibuprofen.

Animals↗
PubMed1995

Smoke inhalation causes a delayed increase in airway blood flow to primarily uninjured lung areas.

OBJECTIVE: Single lung inhalation injury causes tissue damage to the contralateral lung. We therefore examined airway blood flow after smoke inhalation in chronic instrumented sheep to get further information about the underlying pathophysiology. DESIGN/PATIENTS: The right lung and lower trachea of 5 animals were smoke-exposed, while their left lung was air-insufflated using a split ventilation technique. Three animals, where both lungs were only air-insufflated, served as controls. Blood flow to the airway was measured using a labeled microsphere technique. All animals were studied for 24 h following smoke inhalation. Then they were sacrificed and their tissues harvested. RESULTS: The airway blood flow to the smoke-exposed lung was elevated 11-fold immediately after inhalation injury. The bronchial blood flow to the air insufflated lung became significantly elevated 24 h post-smoke, although to a lesser extent. The control animals did not show any changes of bronchial blood flow during the observation time. CONCLUSIONS: Damage to one lung can lead to pathophysiologic changes in the contralateral lung. This response appears to be mediated by hematogenous factors.

Analysis of Variance↗
PubMed1995

Pulmonary blood flow regulation: influence of positive pressure ventilation.

Positive pressure ventilation with PEEP has been reported to reduce hypoxic pulmonary vasoconstriction (HPV) and thus increase venous admixture. This effect was investigated in six chronically instrumented unanesthetized healthy sheep. The change in left pulmonary arterial blood flow (Qlpa, ultrasonic transit time) in response to unilateral lung hypoxia (10 min of N2 alternately to the left (LLH) and right lung (RLH) was evaluated during mechanical ventilation with and without PEEP of 10 cm H2O in comparison to spontaneous breathing. In the spontaneously breathing animal and during mechanical ventilation without PEEP, Qlpa decreased during LLH from 30% to 16% of cardiac index, during RLH it increased to 51%. With 10 cm H2O of PEEP, Qlpa showed an identical reaction to hypoxia both in the left and right lung. It is concluded that mechanical ventilation and PEEP up to 10 cm H2O does not interfere with pulmonary blood flow regulation to hypoxia.

Animals↗
PubMed1995

Pentafraction for superior resuscitation of the ovine thermal burn.

OBJECTIVE: To determine if a new hydroxyethyl starch, pentafraction, will cause better capillary retention of fluid in thermally burned and nonburned tissues when compared with some currently used volume expanders. DESIGN: Randomized, controlled, experimental study. SETTING: University research laboratory. SUBJECTS: Twenty-one healthy adult range ewes. INTERVENTIONS: Sheep, surgically prepared for chronic study, were randomly assigned to one of three colloid groups for the resuscitation of thermal injuries: a) ovine fresh-frozen plasma group; b) pentastarch group; and c) pentafraction group. Twenty-one sheep were subjected to a 40% total body surface, third-degree flame burn under anesthesia (1.5% to 2% halothane). When awakened, the sheep received 15 mL/kg of one of the above colloids, and then lactated Ringer's solution (2 mL/hr/kg). All animals survived and were killed at 48 hrs after burn injury. MEASUREMENTS AND MAIN RESULTS: We found that cardiac index decreased and systemic vascular resistance increased in the pentastarch and plasma groups. However, cardiac index increased in the pentafraction group, while systemic vascular resistance increased by only half as much as in the other two groups. Cardiac index in the plasma group decreased significantly for the first 8 hrs, and did not return to the baseline value for 48 hrs. Systemic vascular resistance increased significantly for the first 8 hrs in both the plasma and pentastarch groups. Prefemoral lymph flow was significantly more increased in the pentastarch group, while the lung lymph/plasma oncotic gradient was maintained only by the pentafraction group. CONCLUSIONS: Pentafraction is as good, or even superior, for volume resuscitation in the burn patients, when compared with pentastarch and plasma. This conclusion is made most evident by the attenuated changes in systemic vascular resistance and cardiac index. Pentafraction decreases the fluid flux and potential subsequent edema significantly in burned tissues and effectively maintains the pulmonary microvascular integrity.

Animals↗
PubMed1995

Hypertonic acetate dextran achieves high-flow-low-pressure resuscitation of hemorrhagic shock.

OBJECTIVE: For resuscitation of hemorrhagic hypovolemia, we compared the effectiveness of (1) isotonic lactated Ringer's solution (LRS), (2) 2400 mOsm of 7.5% NaCl:6% dextran 70 (HSD), and (3) 2400 mOsm of 7.9% sodium acetate:1.9% NaCl:6% dextran 70 (HAD). DESIGN: In six randomized, blinded experiments for each solution, conscious instrumented adult sheep were hemorrhaged by removing approximately 1.8 L (42 +/- 3 mL/kg) of blood, while maintaining the mean arterial pressure (MAP) at 50 mm Hg for 2 hours. METHODS: Test solutions were infused as needed to restore the cardiac index to baseline. RESULTS: Volume requirements with HAD (236 +/- 29 mL) and HSD (244 +/- 39 mL) were significantly less (p < 0.05) than LRS (3463 +/- 234 mL). Mean arterial pressure was normalized with HSD and LRS, but not with HAD, which resulted in MAPs of 20 to 25 mm Hg less than baseline resulting from a reduced peripheral resistance. Oxygen delivery, however, was significantly higher with HAD during the resuscitation period. Acid-base balance (pH) and oxygen consumption were normalized within 5 minutes of infusion only with HAD. CONCLUSIONS: Small-volume infusion with HAD resulting in "high-flow-low-pressure" resuscitation may offer unique hemodynamic and metabolic advantages for the initial treatment of hemorrhage from trauma.

Acetates↗
PubMed1995

Effect of phenytoin on smoke inhalation injury in sheep.

To determine whether the anti-inflammatory effects of phenytoin might reduce cardiopulmonary dysfunction we studied the effects of phenytoin treatment on acute lung injury induced by smoke inhalation. Twenty-one chronically instrumented sheep were observed for 24 h after smoke inhalation injury. Myocardial contractility was evaluated by left ventricular end-systolic pressure-diameter relationship (LVESPDR) with a pair of ultrasonic transducers and strain-gauge transducer. In the control group (n = 6), uninjured sheep were given a bolus of phenytoin (12.5 mg/kg). Smoke-insufflated sheep were divided into nontreatment (n = 7) and phenytoin (n = 8) groups. Phenytoin alone had no effects in uninjured sheep except an early rise in heart rate and LVESPDR. In the group given smoke without treatment, there was a significant increase in pulmonary artery pressure and pulmonary vascular resistance index and a decrease in cardiac index. Pulmonary vascular changes were attenuated by treatment with phenytoin. Pulmonary transvascular fluid flux was evaluated by using a lung lymph fistula. LVESPDR fell in the smoke group but not in the group given phenytoin. There was a marked increase in lung lymph flow with smoke inhalation but this phenomenon was not affected by phenytoin treatment. In conclusion, phenytoin treatment reduced early hemodynamic depression.

Animals↗
PubMed1995

S-ethylisothiourea, a nonamino acid inhibitor of nitric oxide synthase, reverses septic vasodilation in sheep.

S-ethylisothiourea (3936W92) is a nonamino acid antagonist of nitric oxide synthase. Its selectivity for the inducible form of nitric oxide synthase is twice as high as for the constitutive form of the enzyme. We tested 3936W92 in 20 sheep, which were surgically prepared for chronic study. In all sheep, a hyperdynamic sepsis was induced by a continuous infusion of live Pseudomonas aeruginosa. After 24 h of sepsis, nine sheep received a continuous infusion of 3936W92 over the next 24 h, whereas the control group (n = 9) received saline instead. Two sheep died within the first 24 h of sepsis. 3936W92 caused a complete reversal of the hyperdynamic circulation, while sheep in the control group remained hyperdynamic. Although the cardiac index decreased significantly during treatment with 3936W92 (7.9 +/- .8 vs. 6.0 +/- .7 l/min/m2), a simultaneous increase in oxygen extraction prevented oxygen consumption from falling.

Animals↗
PubMed1995

Increased plasma glucose clearance in sepsis is due to increased exchange between plasma and interstitial fluid.

It has long been unclear why plasma glucose clearance is increased during sepsis, an insulin-resistant state. To address this issue, we studied sheep given a constant infusion of endotoxin for at least 24 h (n = 5). We gave a bolus of 6,6 d2 glucose and determined the fractional exchange of glucose between plasma and interstitial fluid using compartmental modeling techniques. We found that exchange of glucose between plasma and interstitial fluid was significantly increased in sepsis, but the fractional clearance of glucose from interstitial fluid was not significantly altered. Thus the observed increased plasma glucose clearance was solely due to alterations in glucose exchange between plasma and interstitial fluid and was unrelated to glucose transport into cells.

Animals↗
PubMed1995

Chronic lung lymph fistula that only drains the left lung.

We developed a chronic lung fistula that drains only the left lung, allowing for evaluation of injury in a single lung. To remove lymph drainage from the right lung into the caudal mediastinal lymph node, the right lower pulmonary ligament was severed. Pneumatic occluders were placed on the left pulmonary arteries and veins. To ensure that lymph drained from only the left lung, we increased the right pulmonary arterial pressure (RPAP) from 21.2 +/- 0.5 to 36.5 +/- 0.6 mmHg. The left pulmonary arterial pressure (LPAP) was kept at wedge pressure level for 1 h by inflating pneumatic occluders. Lymph flow from the left lung fistula was stable during this occlusion. Six hours after recovery was increased the LPAP from a baseline level of 19.1 +/- 1.0 to 36.4 +/- 0.9 mmHg and the RPAP from 21.2 +/- 0.5 to 38.0 +/- 0.8 mmHg for 2 h by inflating the pneumatic occluders on the left and right pulmonary veins. Lymph flow increased from 5.3 +/- 1.0 to 28.0 +/- 2.9 ml/h. Reflection coefficient was calculated at 0.80 +/- 0.02.

Animals↗
PubMed1995

Effects of manganese superoxide dismutase on lung fluid balance after smoke inhalation.

There is evidence of increased oxygen free radical activity after smoke inhalation with and without concomitant burn injury. We determined the effects of manganese superoxide dismutase (Mn SOD) on lung fluid balance as measured by lung microvascular permeability coefficient (sigma), filtration coefficient (Kf), and lymph flow. Merino breed ewes (n = 6/group) were surgically prepared. The SOD group (SOD) received Mn SOD (9,000 U/kg) as an intravenous bolus and was insufflated with smoke. The control group (CON) received saline and smoke. sigma and Kf were determined 24 h before and 24 h after smoke injury. Lymph flow, arterial O2-to-inspired O2 fraction ratio, systemic hemodynamics, and pulmonary arterial and capillary pressures were measured. The sigma was significantly (P < 0.05) higher after smoke insufflation in SOD compared with CON (0.71 +/- 0.03 vs. 0.53 +/- 0.05). Kf was significantly lower after smoke insufflation in SOD compared with CON (0.038 +/- 0.010 vs. 0.061 +/- 0.010). Lymph flows were significantly lower during the 24 h after smoke insufflation in SOD compared with CON (33 +/- 7 vs. 55 +/- 8 ml/h at 24 h). Arterial O2-to-inspired O2 fraction ratio was significantly improved at 6 and 12 h after smoke insufflation in SOD compared with CON at the same time points. Mn SOD meliorates the lung microvascular permeability changes associated with smoke inhalation injury.

Administration, Inhalation↗
PubMed1995

Effects of bafilomycin A1 on cytosolic pH of sheep alveolar and peritoneal macrophages: evaluation of the pH-regulatory role of plasma membrane V-ATPases.

The role of plasma membrane V-ATPase activity in the regulation of cytosolic pH (pHi) was determined for resident alveolar and peritoneal macrophages (m theta) from sheep. Cytosolic pH was measured using 2',7'-biscarboxyethyl-5,6-carboxyfluorescein (BCECF). The baseline pHi of both cell types was sensitive to the specific V-ATPase inhibitor bafilomycin A1. Bafilomycin A1 caused a significant (approximately 0.2 pH units) and rapid (within seconds) decline in baseline pHi. Further, bafilomycin A1 slowed the initial rate of pHi recovery (dpHi/dt) from intracellular acid loads. Amiloride had no effects on baseline pHi, but reduced dpHi/dt (acid-loaded pHi nadir < 6.8) by approximately 35%. Recovery of pHi was abolished by co-treatment of m theta with bafilomycin A1 and amiloride. These data indicate that plasma membrane V-ATPase activity is a major determinant of pHi regulation in resident alveolar and peritoneal m theta from sheep. Sheep m theta also appear to possess a Na+/H+ exchanger. However, Na+/H+ exchange either is inactive or can be effectively masked by V-ATPase-mediated H+ extrusion at physiological pHi values.

Animals↗
PubMed1995

Use of nitric oxide synthase inhibitors in animal models of sepsis.

Sepsis, as a general inflammatory process, affects the whole organism, mainly because of the intense vasodilation and reduced perfusion pressures associated with it. The high mortality rates seen with sepsis are correlated with a reduction in mean arterial pressure. Therefore, the restoration of adequate arterial pressures is imperative. Nitric oxide (NO.) is at least partly responsible for the vasodilation. Inhibition of nitric oxide synthase (NOS) is, therefore, a logical approach for the treatment of sepsis. As with any other vasoconstrictive drug, NOS inhibitors are clinically indicated only in hyperdynamic sepsis. In animal models, their administration leads to an immediate restoration of blood pressure, accompanied by improved myocardial, pulmonary, and renal function. An increase in oxygen extraction prevents oxygen consumption from decreasing, despite a marked reduction in cardiac output to normal concentrations. In sepsis, virtually all regional blood flows are increased. In our experiments, no organ systems showed a reduction below preseptic baseline values when NOS inhibitors were administered. Furthermore, NOS inhibition did not cause an increase in lactate concentrations, indicating adequate nutritive organ blood flow. Consequently, NOS inhibitors seem to be beneficial and safe when administered under the right circumstances and in a controlled fashion.

Amino Acid Oxidoreductases↗
PubMed1995

Endotoxin versus bacteremia: a comparison focusing on clinical relevance.

All phenomena seen under ovine endotoxemia or bacteremia are typically observed in septic humans as well. The lethality (approximately 20%) in both sepsis models underlines the severity of the experimental sepsis in these models. As mentioned above, both models are ideal to objectify the effects of new therapeutic approaches for the treatment of sepsis, because they provide stable conditions. We tested the inhibition of nitric oxide synthase in both models: Nitric oxide is the main mediator of the vasodilation and the hyperdynamic circulation seen in sepsis. Since the restoration of the perfusion pressure is the major therapeutic goal to prevent further tissue damage (Chernow et al. 1990), the blockade of the nitric oxide synthase seems to be a logical approach for the treatment of hyperdynamic sepsis. Therefore, we tested the nitric oxide synthase inhibitor N(W)-nitro-L-arginine methyl ester (L-NAME) in the endotoxemic sheep model as well as in the bacteremic model. L-NAME reversed the hyperdynamic circulation of sepsis (Meyer et al.1992; Dehring et al.1993). The cardiac output was lowered back to baseline, and at the same time, the arterial pressure was elevated to baseline niveau, both resulting in a marked increase in systemic vascular resistance (figure 3). The pulmonary artery pressure showed only a slight increase, but due to the marked reduction in cardiac output the pulmonary vascular resistance increased significantly. The oxygen extraction was elevated to an extent, which prevented the oxygen consumption to fall, although the oxygen delivery dropped significantly because of the lowered cardiac output (figure 4). The intrapulmonary shunt was brought back to baseline (Meyer et al.1994a), allowing an improved pulmonary oxygen uptake. The renal function improved significantly after nitric oxide synthase inhibition in endotoxemia as well as in bacteremia (Hinder et al.1994; Lingnau et al.1994). Not only was the creatinine clearance elevated, but the urine output also increased, lowering the positive fluid balance. Another inhibitor of nitric oxide synthase N(W)-Mono-Methyl-L-Arginine (L-NMMA) was recently tested in these models as well. This drug is now already in clinical trials. The fact that the effects of these nitric oxide synthase inhibitors in septic humans are similar to the effects in the described experimental sepsis models proves the clinical relevance of the endotoxemic and the bacterimic sheep model.

Animals↗
PubMed1994

IVOX with gradual permissive hypercapnia: a new management technique for respiratory failure.

IVOX (intravenous oxygenator and CO2 removal device) augments venous gas exchange in patients with severe respiratory failure. Controlled hypoventilation with permissive hypercapnia reduces airway pressures during mechanical ventilation and augments CO2 exchange through the IVOX. To quantify the additive effects of gradual permissive hypercapnia and IVOX on gas exchange and reduction of airway pressures, 13 adult sheep underwent tracheostomy and severe smoke inhalation injury. Seven were mechanically ventilated alone (control), and six had mechanical ventilation, systemic anticoagulation, and implantation of IVOX (size 7 with 0.21-m2 surface area) (IVOX group). Both groups were anesthetized and paralyzed for 24 hr. In the IVOX group, minute ventilation was decreased in a stepwise fashion to produce a gradual increase in PaCO2, from 30 to 95 mm Hg, over 12 hr, and then sustained for an additional 12 hr. Sodium bicarbonate was given intravenously as necessary to keep arterial pH above 7.25. There were no significant differences in mean arterial pressure, cardiac output, or pulmonary artery pressure between the two groups. In the IVOX/permissive hypercapnia group, IVOX CO2 removal increased as a linear function of PaCO2 (y = 0.87x + 8.99, R2 = 0.80). IVOX CO2 removal was only 40 ml/min at normocapnia (40 mm Hg) but increased to 91 ml/min when PaCO2 was 95 mm Hg. Both peak inspiratory pressure and minute ventilation of the IVOX/permissive hypercapnia group were significantly lower than the control group, 30 +/- 4 mm Hg vs 51 +/- 3 mm Hg and 3.9 +/- 0.3 liters vs 8.4 +/- 0.5 liters (P < 0.05) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗