G. Schweitzer

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)

Bronchoalveolar lavage fluid and plasma proteins, chemiluminescence response and protein contents of polymorphonuclear leukocytes from blood and lavage fluid in traumatized patients.

The technique of bronchoalveolar lavage was used to obtain serial samples of lavage every two days from non-contused lung areas of seven traumatized patients and four normals; blood was drawn simultaneously. Urea, total protein, albumin, alpha 1-proteinase inhibitor, alpha 2-macroglobulin, lactate dehydrogenase, beta-N-acetyl-glucosaminidase, myeloperoxidase, and elastase enzyme activity, as well as complexed and total elastase concentrations were determined in bronchoalveolar lavage fluids and plasma samples. Lavage fluid cell pattern was counted. Polymorphonuclear leukocytes were isolated from lavage fluids and blood samples. Granulocyte contents of elastase enzyme activity, complexed and total elastase concentrations, and myeloperoxidase and lactate dehydrogenase activity were determined. Polymorphonuclear leukocyte stimulatory functions were measured by luminol-enhanced chemiluminescence. The following results were obtained for the patient group: Patterns of lavage fluid cells were shifted in favour of polymorphonuclear leukocytes and lymphocytes. The protein determinations of bronchoalveolar lavage fluids and plasma samples gave information about the extent of alterations of permeability of the capillary-interstitial-alveolar space (albumin/urea and alpha 1-proteinase inhibitor/urea ratios) as well as about the amounts of cytoplasmic and lysosomal enzymes released by phagocytes (lactate dehydrogenase/urea, beta-N-acetylglucosaminidase/urea, elastase/urea ratios). Polymorphonuclear leukocytes isolated from bronchoalveolar lavage fluids contained a decreased content of myeloperoxidase and elastase enzyme activities and total elastase concentration; the content of complexed elastase was found to be increased more than 100 fold. From chemiluminescence measurements there was evidence for decreased zymosan-induced stimulatory function, while the photon emission rate of polymorphonuclear leukocytes after passage into the alveolar space was increased.

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

Abstract Our aim was to investigate whether ascorbic acid can reduce reactive oxygen metabolite‐mediated acute lung injury.

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.

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.

Pathomechanisms of the adult respiratory distress syndrome (ARDS): Chemiluminescence analysis of polymorphonuclear leukocytes

ConclusionsAs measured by the luminol enhanced chemiluminescence stimulated by zymosan A the posttraumatic stimulatory response was increased in blood derived and decreased in BAL derived PMNL as compared to normals. This loss of metabolic function is paralleled by an increased extracellular release of respiratory burst products and lysosomal enzymes from stimulated and phagocytosing PMNL during their capillary-interstitial-alveolar passage. These events seem to be part of the pathogenetic mechanisms that contribute to the lung injury in ARDS. The observed shortening of photon emission times is supposed to be caused by C3b receptor affinity and/or concentration increase during the in vivo PMNL stimulation and migration across the blood/air barrier as a result of the attempt to compensate for the disappearing response ability.

Suppression of the neutrophil chemiluminescence response in blood of multiply traumatized patients with and without the adult respiratory distress syndrome (ARDS)

ConclusionsFrom the results, alterations of humoral and cellular components of the nonspecific immune system were supposed to be involved in the ARDS pathogenesis. Concerning the intravascular compartment, a plasma opsonin defect could be observed, especially for group C patients with a later EVLW increase. Furthermore, these patients demonstrated a continuous synthesis of a trauma factor that suppressed CL responses and presumably also phagocytosis/killing functions of PMNL in blood, hereby predisposing this patient group to sepsis and sepsis-amplified ARDS development. Such an inhibition factor has been described by Lanser et al. [5] in septic patients, but our results demonstrated that this factor seemed always to be synthetized after a traumatic event irrespective of septicemia. As a consequence, the increased endogenous respiratory burst potential of neutrophils, especially of patients with a later EVLW increase, becomes effective after the neutrophil has left the capillary and entered the alveolar space, no longer being kept in check by the trauma factor and then liberating the complete set of inflammation mediators for lung structure damage.

Prostaglandin E1 Inhibits the Stimulation of Neutrophils In Vitro and In Vivo and Improves Cardio-Respiratory Functions in Multiply Traumatized Patients at Risk of Adult Respiratory Distress Syndrome

The trauma-induced activation of granulocytes (PMN) and their functional alterations (increase in adherence, extracellular release of reactive oxygen derived agents and lysosomal enzymes) are believed to play a central role in the initiation and amplification of capillary endothelial cell (EC) damage and organ failure such as that in adult respiratory distress syndrome (ARDS) [1]. Prostaglandin E1 (PGE1) is known to inhibit several PMN functions involved in these processes. Because of this and its vasodilating actions, the immunomodulator PGE1 seems a promising agent for the treatment of ARDS patients. Clinical trials were therefore started in recent years; however, the expected beneficial effects were not observed, presumably because of beginning the PGE1 treatment only after the diagnosis of ARDS [2, 3]. Our study design called for treating patients at risk of ARDS before the onset of the disease to prevent or minimize very initial pathogenetic reactions of activated granulocytes by early PGE1 infusion therapy. Additionally, the effects of PGE1 on essential functions of granulocytes (adherence, oxygen radical production, enzyme release) and on EC/PMN interactions were investigated to enable a uniform and critical judgement about the proposed therapeutic approach and underlying patho-mechanisms.

Die Wirkung von Prostaglandin E1 auf nichtspezifisches Immunsystem, Komplementaktivierung, Lungenfunktion und Hämodynamik bei Polytrauma-Patienten mit ARDS-Risiko

Die Trauma-induzieite Aktivierung von Granulocyten und Komplementsystem wird als wesentliche Ursache fur die Pathogenese des posttraumatischen progressiven Lungenversagens (ARDS) angesehen [1]. Die Richtigkeit des therapeutischen Konzepts der Hemmung granulocytarer Funktionen (Sauerstoffradikal-Bindung, Sekretion lysosomaler Enzyme) mit PGE1 hat sich in mehreren klinischen Studien bisher nicht eindeutig nachweisen lassen, da PGE1 ausnahmslos erst nach der Diagnose des schon manifesten ARDS gegeben wurde [2, 3]. Daher wurde PGEl bei Polytrauma-Patienten mit ARDS-Pradisposition unmittelbar nach Trauma 6 Tage lang randomisiert, doppelblind und Placebo-kontrolliert infundiert.