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Biomedical subjects

A Dwenger

Publications and source records attributed to A Dwenger.

At least 37 records · Page 2Linked to original sources
PubMed1994

Ascorbic acid reduces the endotoxin-induced lung injury in awake sheep.

Our aim was to investigate whether ascorbic acid can reduce reactive oxygen metabolite-mediated acute lung injury. The effects of intravenous administration of Escherichia coli endotoxin were studied, with and without ascorbic acid infusion, on haemodynamics, lung lymph flow, cardio-respiratory and neutrophil function in chronically instrumented sheep. Paired experiments were performed on eight sheep in which they received either endotoxin alone (0.5 micrograms kg-1 b.w.) (ET group) or in combination with an ascorbic acid infusion (1 g kg-1 b.w. bolus injection followed by 0.2 g kg-1 h-1 continuous infusion) ET + ASC group) in random order. Four of the animals also received ascorbic acid alone (ASC group). As a result, for the ET + ASC group a general and mostly significant improvement (P < 0.05) in the early hypertensive phase (0-60 min, P values) and in the late permeability phase (2-4 h, *P values) of cardiorespiratory function (mean artery pressure: P/*P = 0.283/0.049; mean pulmonary artery pressure: P/*P = 0.0001/0.0001; mean pulmonary artery wedge pressure: P/*P = 0.012/0.001; right ventricular stroke work index: P/*P = 0.02/0.0001; cardiac index: P/*P = 0.797/0.755; arterial oxygen saturation: P/*P = 0.0059/0.01; arterial-venous difference of oxygen tension: P/*P = 0.011/0.0005), oxygen consumption: P/*P = 0.013/0.035, lung lymph flow: P/*P = 0.562/0.012, lymph/plasma protein ratio: P/*P = 0.304/0.008 and protein clearance: P/*P = 0.56/0.05 was observed in comparison with the ET group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Influences of different methods of intramedullary femoral nailing on lung function in patients with multiple trauma.

We investigated the effects of primary (< or = 24 h) intramedullary femoral nailing on lung function and pulmonary hemodynamics in patients with multiple trauma. Two groups were separated: the group with primary femoral nailing with reaming (group RFN) was submitted to femoral nailing after reaming of the medullary canal; in the group with unreamed femoral nailing (group UFN) a small-diameter solid nail was inserted without reaming. Lung function was assessed by oxygenation ratio (PaO2/FIO2), and pulmonary hemodynamics by intraoperative pulmonary artery catheter measurements. Central venous blood concentrations of elastase and the platelet count were determined during and 3 days after surgery. Lung function was stable in UFN patients (n = 14), but deteriorated in RFN patients (n = 17) from 353 +/- 24 (PaO2/FIO2 preoperatively) to 260 +/- 28 (PaO2/FIO2 postoperatively) (p < 0.05) and improved only after 48 hours. Pulmonary artery pressure (PAP) did not change during surgery in UFN patients; in RFN patients PAP increased from 27.2 +/- 3.1 mm Hg (preoperatively) to 36.3 +/- 4.1 mm Hg (p < 0.05) upon reaming and normalized 1 hour after insertion of the nail. Femoral nailing after reaming represents a potential risk with respect to lung function disturbances. This might trigger the development of adult respiratory distress syndrome (ARDS), especially in patients at extra risk of this complication (additional lung contusion, "borderline patient"). In these cases unreamed femoral nailing might offer an alternative by allowing primary intramedullary stabilization without the risk of adverse effects to the lung.

Adult↗
PubMed1992

Pulmonary damage after intramedullary femoral nailing in traumatized sheep--is there an effect from different nailing methods?

Stabilization of femoral shaft fractures is a controversial issue in the management of patients with multiple trauma. Intramedullary nailing usually is preferred primarily; in recent years, however, pulmonary complications (e.g., ARDS) have been reported that were attributed to the reaming procedure. To study the effects of different nailing methods in a model of severe trauma, hemorrhagic shock and lung contusion were created at day 1 in sheep prepared by the method described by Staub. After recuperation (day 3) the animals in the study group (group 1) underwent intramedullary nailing of a closed femur without prior reaming; group 2 was treated with reaming and nailing according to AO standards. The reaming procedure led to an acute increase of pulmonary arterial pressure only in group 2 (19.8 +/- 2.1 to 31.0 +/- 4.6 mm Hg). Pulmonary triglyceride levels increased at parallel time points from 18.27 +/- 2.3 to 33.04 +/- 7.37 mg/dL only in group 2. Stimulatory capacity of polymorphonuclear leukocytes (PMNL) increased in the study group and decreased in controls (group 1: 2.652 +/- 0.23 x 10(6) cpm to 3.387 +/- 1.34 x 10(6) cpm; group 2: 2.699 +/- 0.34 x 10(6) cpm to 2.460 +/- 0.187 x 10(6) cpm). Intramedullary nailing caused an increase of lung capillary permeability in both groups; in the study group less damage was seen (group 1: 0.390 +/- 0.0006 to 0.354 +/- 0.011; group 2: 0.391 +/- 0.0004 to 0.336 +/- 0.015; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗
PubMed1992

Effect of recurrent endotoxemia on hemodynamics, lung function and neutrophil activation in sheep.

The aim of the study was to find out in which way lung permeability and polymorphonuclear leukocyte (PMNL) functions are modulated under recurrent endotoxin challenge, as it might occur in clinical septic patients. In a sheep model with chronic lung lymph fistula, performing bronchoalveolar lavage (BAL), we investigated the relationship between PMNL function and endothelial as well as epithelial damage in the lung in a sepsis syndrome, using a protocol of recurrent endotoxemia induced by 1 microgram/kg body weight Escherichia coli endotoxin treatment every 12 h over a 5-day period. Pulmonary response showed constantly increased pulmonary arterial pressure at mean values of 24-30 mm Hg. Also, lymph flow did not return to baseline, but remained on a level of 6-9 ml/30 min, after an increase to 12-15 ml/30 min following each endotoxin injection. In contrast, a lower increase in protein clearance was noted upon subsequent endotoxin administration. After initial values of 7-8 ml/30 min following the first endotoxin injection, almost baseline values were measured on the 5th day (3-4 ml/30 min). In systemic hemodynamics, we noted a decrease in cardiac output to 3.0 l/min after the first endotoxin injection, followed by a significant increase to 7 l/min under subsequent endotoxin administration. In PMNL function, we observed an attenuation of the acute response of the decrease in PMNL count, in vitro chemiluminescence response and plasma beta-N-acetylglucosaminidase level. The plasma urea concentration revealed a transient reduction in kidney function. In the epithelial lining fluid (ELF) of the alveoli, total cell count did not change significantly, but the fraction of PMNL increased from 2 to 20% during the 5 days. The ELF/plasma ratios of albumin and total protein did not change significantly. In conclusion, recurrent endotoxemia in a sheep model can produce a hyperdynamic state like in a sepsis syndrome which is further characterized by an initial leakage of the endothelial barrier, only minor affection of the epithelial barrier and by an exhaustion of PMNL function.

Animals↗
PubMed1992

Effect of ascorbic acid on neutrophil functions and hypoxanthine/xanthine oxidase-generated, oxygen-derived radicals.

The chemiluminescence of isolated neutrophils, stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine, latex, lipopolysaccharide from Escherichia coli, zymosan A, or 4 beta-phorbol 12 beta-myristate 13 alpha-acetate was inhibited up to 99% by the dose-dependent oxygen radical scavenging activity of 6 mmol/l ascorbic acid. The chemiluminescence of neutrophils in blood, stimulated with 4 beta-phorbol 12 beta-myristate 13 alpha-acetate, or with zymosan A was inhibited 35% or 48%, respectively, by 6 mmol/l ascorbic acid. Ascorbic acid, up to 6 mmol/l, did not inhibit the release of beta-N-acetylglucosaminidase and elastase from isolated neutrophils activated by the above stimulatory agents. During neutrophil/nylon fibre interaction ascorbic acid reduced the oxygen radical production dose-dependently (77% inhibition of the chemiluminescence response at 6 mmol/l ascorbic acid), whereas the adherence was unaffected. Hypoxanthine/xanthine oxidase-generated oxygen radicals were scavenged by ascorbic acid in a dose-dependent manner (99% inhibition of the chemiluminescence response at 100 mumol/l ascorbic acid). From these results, ascorbic acid can highly be recommended for animal experiments and clinical studies in patients with trauma, shock and sepsis and for studies to prevent or reduce reperfusion injuries.

Antioxidants↗
PubMed1992

[Effects of different intramedullary stabilizing procedures of the femur on lung function in polytrauma].

We investigated the effects of primary (< 24 h) intramedullary femoral nailing on lung function and pulmonary hemodynamics in multiple trauma patients. The standard procedure following reaming of the medullary canal (AFN) was compared with a new procedure using a small, solid nail without prior reaming (UFN). Pulmonary hemodynamics were determined using a pulmonary artery catheter. Global lung function was assessed by means of the oxygenation ratio (PaO2/FiO2). Concentrations of elastase and the platelet count as a general parameter of the clinical course were determined from central venous blood during and 3 days after surgery. The lung function was stable in UFN patients (n = 6), but decreased significantly in AFN patients (n = 10) from 353 +/- 24 (PaO2/FiO2 preoperative) to 260 +/- 28 (PaO2/FiO2 postoperative) and did not improve until 48 h later. Pulmonary artery pressure (Pap) remained within normal limits in UFN patients, whereas in AFN patients Pap increased from 27.4 +/- 3 mm Hg (preoperative) to 37 +/- 3 mm Hg during reaming and did not normalize until 1 h after insertion of the nail. The platelet count remained unchanged in UFN patients and dropped in AFN patients from 143 +/- 25 x 1000 cells/ml blood (preoperative) to 87.5 +/- 15 x 1000 cells/ml blood 2 days after surgery. Our measurements did not show an increase in central venous triglycerides in the AFN group, probably because bone marrow does not become immediately soluble. There was no significant difference between the increase of elactase levels in the two groups. The femoral nailing procedure with reaming in multiple trauma patients involves a potential risk to the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Phagocytic cell function in recurrent endotoxemia in sheep.

Sepsis syndrome in severely traumatized patients is supposedly due to a blockade of the phagocytic cell system--for example, the reticulo endothelial system (RES) and polymorph nuclear leukocytes (PMNL), which cause insufficient elimination of bacterial substances (e.g., endotoxin). In contrast we found in a previous study using a model of acute endotoxemia that RES clearance is enhanced, while PMNL function gave evidence for decompensation. In order to clarify whether or not our results were just a matter of single dose endotoxemia, we have investigated RES and PMNL function in a sheep model with recurrent endotoxemia. A sheep receiving endotoxin at a dose of 1 microgram/kg body weight every 12 hours was monitored over a 5-day period. RES clearance was calculated by the half-life of Tc99 phytate each day. The PMNL function was determined by measuring chemiluminescence (CL) of isolated PMNL and total blood. The half-life of Tc99 phytate decreased from 56 min to 44 min with endotoxin (P less than or equal to 0.01) the second day and further to 42 min (P less than or equal to 0.002) on the third day. Values then returned to baseline until the end of study. Zymosan induced and luminol enhanced CL response indicated an acute cellular exhaustion after the first endotoxin dose. Under subsequent endotoxin administration, a daily attenuation of the acute response was noted in combination with baseline opsonin capacity. Our results give evidence that also in recurrent endotoxemia RES function is characterized by a sufficient clearance, whereas the PMNL function remains decreased and therefore possibly is responsible for the well-known clinical post-traumatic septic complications.

Animals↗
PubMed1992

Determination of human neutrophil elastase in bronchoalveolar lavage fluid: homogeneous immunoactivation versus heterogeneous enzyme immunoassay.

Elastase mass concentrations of bronchoalveolar lavage fluid were determined by a homogeneous immunoactivation and a heterogeneous enzyme immunoassay. There was an excellent correlation between both assay systems (y = 1.0376 . x + 1.311; r = 0.9901; n = 43) indicating the suitability of the immunoactivation method for the determination of elastase concentrations in bronchoalveolar lavage fluid as a matrix. Furthermore, dilution of bronchoalveolar lavage fluid samples did not influence the elastase recovery of either assay system.

Bronchoalveolar Lavage Fluid↗
PubMed1991

Relationship between proteolytic enzymes and atherosclerosis in aortic aneurysms.

Aortic elastase and aortic collagenase were assayed in 38 patients who underwent an operation for thoracic or infrarenal aneurysm or infrarenal aortic occlusive disease and in 15 control patients (heart or kidney donors). Elastase was elevated in normal aortas of the infrarenal region (1.10 milliunits per gram, p less than 0.05), and in atherosclerotic descendens aneurysms (1.24 milliunits per gram, p less than 0.05), compared with the ascending aorta, when normal; aneurysmatic specimens revealed similar low elastolytic activities (0.10 milliunits per gram). The highest elastase content was found in infrarenal aneurysms (4.65 milliunits per gram). Collagenase assays yielded no significant differences, although higher activities were extracted from aortas of the infrarenal region. Coexistent atherosclerosis and wall destruction were evaluated by macroscopic and histologic investigation. All infrarenal specimens demonstrated severe atherosclerotic wall degeneration with depletion of elastic fibers. As the atherosclerotic specimens did not differ from normal aortas by protease assay, the higher elastase of infrarenal samples compared with the thoracic aorta suggests a more rapid fiber metabolism in the infrarenal region. The significantly elevated elastolytic activity of infrarenal aneurysms points to the decisive role of elastase in infrarenal aneurysm formation.

Aorta↗
PubMed1991

[Does lung contusion and general injury severity have an effect on the lung following intramedullary femoral nailing? An animal model].

We evaluated changes in lung function after closed intramedullary femoral nailing (IMN) in sheep. The effects of isolated IMN were compared with those of nailing after lung contusion and hemorrhagic shock. In adult female merino sheep a chronic lung lymph fistula was prepared according to the method described by Staub. At day 1, group 1 received right-sided lung contusion and hemorrhagic shock to a mean blood pressure of 50 mmHg for 2 h. Group 2 was the control group. At day 3 both groups were submitted to IMN, followed by a 2-h observation period. IMN caused a transient significant increase in pulmonary artery pressure and central venous triglycerides in both groups. Chemiluminescence of isolated polymorphonuclear leukocytes (PMNL) decreased in group 1 from 2.699 +/- 0.344 to 2.460 +/- 0.187 x 10(6) cpm/25000 PMNL and increased in group 2 from 2.757 +/- 0.127 to 3.824 +/- 0.439 x 10(6) cpm/25000 PMNL. Lymph flow in group 1 increased 1.5-fold while microvascular pressure decreased. In group 2 lymph flow increased less, while MVP increased. The filtration coefficient in group 1 was 5 times (7.533 +/- 0.044) that in the control group (1.45 +/- 0.133). Calculations of permeability indicated a 2-fold increase (0.044 group 1 vs 0.026 group 2). In the presence of previous lung contusion and hemorrhagic shock there is definite lung damage from IMN. This is probably mediated by stimulation of PMNL.

Animals↗
PubMed1990

Alveolar cell pattern and chemiluminescence response of blood neutrophils and alveolar macrophages in sheep after endotoxin injection.

In order to study the pathomechanisms of the Adult Respiratory Distress Syndrome in an acute animal model, we monitored the alveolar cell pattern and the stimulatory chemiluminescence responses of blood neutrophils and alveolar macrophages in sheep after Escherichia coli endotoxin injection (2 micrograms/kg of body weight). Using appropriate bronchoalveolar lavage techniques, thereby avoiding local inflammation, it was demonstrated that endotoxin injection did not cause any recruitment of neutrophils into the alveoli for a period of up to 24 hours. Following endotoxin injection, blood neutrophils showed a maximal stimulatory response after 5 minutes, and alveolar macrophages after 4 hours. It is concluded that if neutrophils are responsible for initiating the increase in microvascular permeability, then this action must be purely intravascular.

Anesthesia↗
PubMed1989

[Humoral and cellular changes of non-specific immune response following severe trauma].

The influence of trauma and hemorrhagic shock on the non-specific immune system has been pointed out in various experimental studies. Other investigations have also been able to find a relationship between these changes and a higher incidence of post-traumatic complications in the form of organ failure. Our aim was to demonstrate the potential changes in the cellular defense system in a clinical study on multiple trauma patients. The polymorphonuclear leukocytes (PMNL) are the main representative of the mobile, non-specific immune system. Our study revealed a significant deterioration of PMNL function after trauma. The metabolic activity and phagocytic function were mainly affected by a decrease in the concentration of so-called "opsonins." The opsonins are important for the identification and engulfment of debris (necrosis, fat emboli and thrombi) and bacterial substances (endotoxin). Next to the opsonin level, a change in the receptor configuration is important for phagocytosis. However, we could not find any substantial evidence of surface receptor alteration. The reticuloendothelial cells (RES), a stationary phagocytic system, also showed a significant reduction in clearance function in these polytraumatized patients. Similar to PMNL, these disturbances were based on the reduction of the opsonine concentration. We were able to demonstrate a significant disturbance in immune function in multiple trauma patients with post-traumatic complications compared to patients with a normal clinical course after injury. Disturbances in the PMNL function (seen after 4 days) were found to appear after the RES disturbances. Systemic interaction between these two phagocytic systems cannot be excluded and further investigation is therefore required.

Adolescent↗
PubMed1987

Phagocytic function of polymorphonuclear leukocytes and the RES in endotoxemia.

The reticuloendothelial system (RES) and the polymorphonuclear leukocytes (PMNs) are thought to play a major role in defense against sepsis. Disturbances in the function of these two phagocytic systems during a septic event is associated with the development of lung capillary injury. Endotoxemia is said to lead to similar changes. Our study examined the function of the RES and PMNs after bolus injection of endotoxin (2 micrograms/kg BW) in a standardized sheep model. For up to 24 hr after endotoxin, blood samples were drawn and PMN function was followed by chemiluminescence, chemotaxis, and adherence as well as the phagocytosis and killing of bacteria. RES function was determined by the blood clearance of a labeled Tc99 colloid. We found an increase of RES clearance directly after endotoxin. Chemotaxis, phagocytosis, and killing were reduced. Adherence was increased. Chemiluminescence peak maximum (CLPM), representing the metabolic activity of the PMNs, was initially increased but shortly thereafter showed a significant decline (at 1 hr: 0.52 +/- 0.13 X 10(6) cpm with P less than 0.05 compared to baseline). The chemiluminescence peak time (CLPT), a measure of membrane receptor function, was significantly reduced (10.0 +/- 2.2 min with P less than 0.001 compared to baseline). Endotoxin led to a reduction of intracellular PMN functions (phagocytosis, killing, CLPM) within 1 hr. Membrane localized functions (adherence, CLPT) were increased. The changes in PMN function might be the reason for the development of lung capillary injury, in spite of undisturbed RES clearance.

Animals↗
PubMed1987

Mechanisms of non-opsonized zymosan-induced and luminol-enhanced chemiluminescence in whole blood and isolated phagocytes.

A luminol-dependent non-opsonized zymosan-induced chemiluminescence method for phagocytes in small quantities of whole blood (40 microliters; final dilution: 1:14) is described. It was characterized with reference to cellular and humoral components, and also applied to isolated neutrophils, eosinophils and monocytes. Normal values for whole blood chemiluminescence and for neutrophils, eosinophils and monocytes are presented. From the chemiluminescence characteristic of distinct phagocytes and their frequency distribution pattern in whole blood, it is concluded that whole blood chemiluminescence has its source predominantly in neutrophils. The question as to the origin of chemiluminescence in phagocytes of whole blood and isolated neutrophils is investigated. The results support the importance of the myeloperoxidase-H2O2-halide system, but also go beyond this. The release of arachidonic acid by phospholipase A2 and of diacylglycerol and inositol trisphosphate by phospholipase C, the metabolism of arachidonic acid by the cyclooxygenase and lipoxygenase pathway, the activation of membrane NADPH oxidase by diacylglycerol and the calcium mobilisation by inositol trisphosphate are necessary for the chemiluminescence reaction. Inhibition of either mechanism suppresses the chemiluminescence response. The interaction of non-opsonized zymosan with plasma opsonins, phagocyte Fc- and complement receptors, respectively, for the initiation of chemiluminescence, was investigated. Non-opsonized zymosan initiates a chemiluminescence response in blood phagocytes in the absence of opsonin from the interaction of the zymosan polysaccharide component glucan with the complement receptor type 3. In the presence of plasma this receptor type also mediates the major chemiluminescence response brought about by the zymosan-coated cleavage products of complement fraction three, iC3b and to a minor degree C3b, while immunoglobulin G-coated zymosan interaction with the Fc-receptor is in this case of minor importance.

Eosinophils↗