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PubMed1979

Circulatory effects of endotoxin on unanesthetized sheep and the response to dopamine.

The cardiovascular effects of endotoxin in the unanesthetized chronically instrumented sheep were investigated. The observations were extended to include the response to intravenous infusions of dopamine to the same sheep at the height of endotoxin action. When the cardiovascular effects of endotoxin in the unanesthetized and anesthetized sheep were compared, there were distinct differences. Unanesthetized sheep tolerated considerably greater dosages of endotoxin. In anesthetized sheep, the compensatory stimulation of the sympathoadrenal system seems to have been blunted and all of the circulatory parameters deteriorate rapidly, ending in death within three hours. In the absence of anesthesia, there was clear evidence of a compensatory sympathoadrenal stimulation, as reflected by the return of most of the circulatory parameters to normal values, and furthermore, the sheep recovered from the effects of endotoxin. The exact mechanism by which anesthesia altered the response of the sheep to endotoxin was not clear. Depression of the baroreceptor and neurohumoral compensatory mechanisms was suggested. The present data indicated that dopamine was a useful agent in correcting the cardiovascular changes brought about by endotoxin.

Anesthesia↗
PubMed1979

Myocardial function in feline endotoxin shock: a correlation between myocardial contractility, electrophysiology, and ultrastructure.

The nature of the myocardial depression observed in patients with septic shock, and in animals late in shock induced by endotoxin, is still under examination. These studies, in cats and kittens administered an LD80 dose of E coli endotoxin, were designed to examine the relationship between changes in myocardial contractility, in cellular electrophysiology and in ultrastructural morphology. There was no difference between tension developed in vitro by cardiac muscle removed from cats five hours after endotoxin administration and from cats not administered endotoxin. There was also no difference in their responses to calcium chloride or to anoxia. The action potential characteristics of ventricular muscle isolated from endotoxin treated cats were also not different from control, and ultrastructural damage was minimal and not extensive. Endotoxin (100 microgram/ml) had no effect on cardiac muscle in vitro, even after a one-hour contact time. It is concluded that the integrity of the myocardium is maintained even late in shock and that endotoxin has no direct effects on the heart.

Action Potentials↗
PubMed1975

[Pathophysiological significance of endotoxins].

The biological activities of endotoxin are manifold. Besides the drop in platelets and the biphasic change in the number of leukocytes, severe disturbances in the capillary bed are among the first changes observed following the administration of endotoxin. It is well known that endotoxins cause the release of various vasoactive mediators. According to our results endotoxins enhance the activity of histamine and serotonin; these findings may contribute to a better understanding of the action of histamine and serotonin in the early post-endotoxin phase. The histamine-sensitizing effect of endotoxins is not prevented by antihistamines. Endotoxins and biogenic amines cause similar disturbances in the capillary bed. The changes that are observed in the content of the vessels, the vessel wall, and the perivascular region are the following: slowing down of the blood stream, degranulation of perivascular mast cells, granulocytosis, wall adhering granulocytes, plasma skimming, rouleaux-formation of erythrocytes, reduction in plasticity of many erythrocytes, acanthocytes, acanthocytosis, appearance of spherocytes and microcytes, and formation of massive aggregates of platelets and of microthrombi. Also, occasionally cell aggregates dissolve and as microemboli form new thrombi. Swelling of pericytes, endothelial, and periendothelial cells is observed, and dissociation and deformation of the endothelial cells occur. By means of contact of the vessel contents with the collagen, there is an additional activation of the coagulation system by factor XII possible. The changes of the epithelial lining and the wall adhering cells enhance the narrowing of the vessel lumen. Prestasis and occasionally stasis occur. One observes increased swelling of the endothelial and periendothelial cells, increased permeability of the vessel wall, passage of plasma and occasionally blood cells, especially erythrocytes, through the endothelium and massive microbleedings. While stasis is observed in the nutritive capillaries, in regions where arteriolar-venular shunts exist the flow continues. The systemic blood pressure may therefore remain unchanged during this phase, although the severe disturbances described occur in the capillary bed. Metabolic alterations, especially in the carbohydrate metabolism are mentioned.

Animals↗
PubMed1984

Desensitization of acute inflammatory lesions to chemotaxins and endotoxin.

Desensitization of the neutrophil inflammatory response to intracutaneous injection of chemotaxins and endotoxin was studied in rabbits. When restimulated 6 hr later with the same agent, inflammatory lesions initiated with platelet-activating factor (PAF), leukotriene B4 (LTB4), or endotoxin supported a diminished influx of neutrophils compared with responses in normal skin. In contrast, repeated stimulation of lesions with alpha-casein failed to lead to desensitization. The specificity of desensitization was investigated, and it was found that lesions initiated with formylmethionyl-leucyl-phenylalanine (FMLP) supported a normal response when restimulated with PAF, alpha-casein, or endotoxin. Initiation of lesions with LTB4, however, diminished the subsequent response to zymosan-activated plasma and PAF, but not endotoxin, alpha-casein, or FMLP. This result indicates that LTB4 is not a final common mediator of neutrophil infiltration of acute inflammatory lesions. Desensitization was detected irrespective of the concentration of chemotaxin used to investigate the response. Repeated stimulation of lesions with FMLP abolished the accumulation of neutrophils after the final stimulus, indicating that complete desensitization can occur and the presence of a chemotaxin within an inflammatory lesion is not sufficient stimulus for neutrophil infiltration of the site to proceed. Lesions initiated with endotoxin supported comparable responses when restimulated with a mixture of FMLP and endotoxin or FMLP alone, despite 93% inhibition of the response to restimulation with endotoxin alone. This indicates that a cell-directed inhibitor of neutrophil migration, such as lipomodulin or neutrophil-immobilizing factor, does not produce the diminished responses in desensitized lesions. It is proposed that desensitization occurs due to down-regulation of a receptor-coupled pathway that permits or facilitates neutrophil extravasation in acute inflammatory lesions. The chemotaxin receptors regulating neutrophil extravasation are probably located on endothelial cells of post-capillary venules.

Acute Disease↗
PubMed1984

Role of peptide leukotrienes and their hepatobiliary elimination in endotoxin action.

The lethal action of endotoxin was studied in mice sensitized against the lipopolysaccharide by D-galactosamine. Protection was obtained by FPL 55712, a selective antagonist of sulfidopeptide leukotrienes, by diethylcarbamazine, an inhibitor of leukotriene biosynthesis, by BW 755C, a dual lipoxygenase and cyclooxygenase inhibitor, and by dexamethasone, which inhibits arachidonate release. Indomethacin incompletely antagonized endotoxin lethality; indoprofen did not protect at all. Leukotriene generation induced by endotoxin in vivo could be demonstrated in rats by employing a radioimmunoassay on bile extracts since intravascular sulfidopeptide leukotrienes were rapidly eliminated into bile. Additionally, however, endotoxin affected the hepatobiliary elimination of sulfidopeptide leukotrienes. From intravenously injected tracer [3H]leukotriene D4, 67% appeared only partially metabolized in bile within 30 min in control rats. Endotoxin and lipid A reduced the biliary [3H]leukotriene D4 secretion by up to 80% while enhancing the hepatic [3H]leukotriene D4 content up to twofold. This inhibition of hepatobiliary elimination was stronger than endotoxin-induced reductions of bile flow or of biliary [14C]taurocholate secretion. Endotoxin, as an activator of the arachidonate cascade, thus potentiates its action in vivo by interfering with the rapid hepatobiliary clearance of sulfidopeptide leukotrienes in addition to stimulating leukotriene and prostanoid formation.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1980

Effects of E coli endotoxin on pancreatic hormones and blood flow.

Studies were performed on anesthetized dogs to determine the relationship between endotoxin-induced alterations in pancreatic blood flow (PBF) and hormones that originate partially or completely from the pancreas. PBF was estimated in six dogs by radioactive microspheres (praeendoxin, 25 and 240 minutes postendotoxin). Insulin, glucagon, pancreatic polypeptide (PP), and somatostatin-like immunoreactivity (SLI) were assayed in arterial and portal venous blood. Cardiac output and mean arterial blood pressure (MABP) decreased 25 minutes after endotoxin administration (50% and 40%, respectively) and returned toward normal levels by four hours. However, there was 74% decrease in PBF at 25 minutes and a further drop four hours after endotoxin. Hormonal responses were characterized by a short-lived increase in arterial insulin, corresponding to a transient increase in blood glucose. Insulin release increased shortly after endotoxin. Arterial glucagon and PP increased two to five hours after endotoxin. There was a suggestion that the increase in PP was of nonpancreatic origin. Little change in plasma SLI was noted following endotoxin. Thus, it appears that endotoxin altered the release of different pancreatic hormones with a variable time courses.

Animals↗
PubMed1983

Granulocyte activation by endotoxin. II. Role of granulocyte adherence, aggregation, and effect of cytochalasin B, and comparison with formylated chemotactic peptide-induced stimulation.

PMN stimulation by endotoxin is heavily dependent on incubation conditions: although marked increase of PMN adhesiveness, enzyme release, and hexose monophosphate shunt activity, as well as superoxide production, occur when endotoxin-challenged cells are incubated in stationary petri dishes, absolutely no such response is observed with cells kept in suspension. Preincubation with cytochalasin B does not alter this reaction pattern. Hyperadhesiveness of endotoxin-challenged PMN is retained after thorough washing, eliminating the possibility that adhesion is due to absorption of endotoxin to petri dishes. In contrast to formylated chemotactic peptides that stimulate PMN adherence as well as aggregation, endotoxin elicits absolutely no aggregatory response (+/- cytochalasin B). Preexposure to endotoxin does not block the aggregatory response to subsequent addition of chemotactic peptides, whereas effects of endotoxin and formylated peptides on PMN in the stationary system are additive. These findings indicate that contact to surfaces is an essential primary event in PMN stimulation.

Cell Adhesion↗
PubMed1980

Myocardial failure and excitation--contraction uncoupling in canine endotoxin shock: role of histamine and the sarcoplasmic reticulum.

Subendocardial and subepicardial sarcoplasmic reticulum (SR) were isolated from five groups of dogs following five hours of hemodynamic monitoring: Group 1, 6-8 mg/kg diphenhydramine (n = 5); Group 2, 0.5 mg/kg histamine phosphate, IV bolus; Group 3, 4.0 mg/kg Escherichia coli endotoxin (n = 5); Group 4, 6-8 mg/kg diphenhydramine, followed by 4.0 mg/kg E coli endotoxin (n = 5); and Group 5, time-matched, sham-operated controls (n = 5). The velocity of calcium uptake and ATP hydrolysis and the integrity of the transport system were determined (coupling ratio = mumoles Ca++/mumoles Pi). Control SR calcium-uptake velocities averaged 1.13 +/- 0.3 mumoles Ca++/mg-min, with no significant difference between the endocardium and epicardium. SR calcium uptake from the endotoxin shock group averaged 0.64 +/- 0.06 (endocardium) and 0.56 +/- 0.05 (epicardium) mumoles Ca++/mg-min (P < 0.01 from control).ATPase activity from the control group = 1.23 +/- 0.04 mumoles Pi/mg-min; and the endotoxin-shocked group exhibited an activity of 0.99 +/- 0.06, with no significant difference between the endocardial and epicardial populations (P > 0.1). Diphenhydramine-control SR calcium-uptake rates averaged 1.12 +/- 0.6 mumoles Ca++/mg-min, with no difference between endocardium and epicardium. Diphenhydramine pretreatment plus endotoxin-shock epicardial SR calcium uptake = 0.94 +/- 0.08 mumoles Ca++/mg-min, while the endocardial SR was significantly depressed at 0.72 +/- 0.04 mumoles Pi/mg-min, with no difference between endocardium and epicardium. Bolus histamine infusion resulted in a small but significant depression of both SR calcium-uptake rates (0.93 +/- 0.04 mumoles Ca++/mg-min) and ATPase activity (0.93 +/- 0.04 mumoles Pi/mg-min), with no significant difference between epicardium and endocardium. This study confirms that the calcium transport system of cardiac sarcoplasmic reticulum isolated from endotoxin-shocked animals is depressed. However, this depression is not due entirely to a depression of the Mg++-dependent, Ca++-stimulated ATPase enzyme, but is also associated with a significant uncoupling of ATP hydrolysis from calcium transport. The histamine blocker, diphenhydramine, was only able to protect the epicardial SR; the endocardial SR still exhibited an uncoupling of ATP hydrolysis from calcium transport. Bolus histamine infusion produced a small but significant depression of both calcium transport and ATP hydrolysis. These results are formulate d into a "proton-lysosome" hypothesis that appears to be able to explain excitation-contraction uncoupling in the endotoxin-shocked myocardium.

Animals↗
PubMed1984

Altered carbohydrate metabolism in endotoxin-tolerant rats after lead sensitization.

The lethality of endotoxin is greatly enhanced in lead-sensitized rats. Previous work showed that hepatic carbohydrate metabolism in lead-treated rats is perturbed by minute endotoxin doses [Fed Proc 41:1607, 1982]. These studies were extended to rats made tolerant to endotoxin by IV injection of lipopolysaccharide (50 micrograms/100 g body weight [BW]) 18 h before simultaneous treatment with lead acetate trihydrate (1.5 mg/100 g BW) and endotoxin (1.0 micrograms/100 g BW). Liver samples removed by freeze-clamping at 5 h from fasted young adult male rats were assayed for glycolytic intermediates. The tolerant rats generally showed smaller alterations in concentrations of metabolites than nontolerant comparison rats challenged with lead and endotoxin. However, phosphoenolpyruvate (PEP) levels were similarly elevated (80-90%) in both groups. The failure of the tolerance procedure to minimize or protect against hepatic PEP changes suggests that the enzymes forming or consuming this metabolite were particularly vulnerable to the action of an endotoxin-released mediator. The fact that some liver glycolytic intermediates remain markedly altered despite amelioration of the lethal effects of endotoxin by the tolerance procedure indicates the existence of independent mediators acting on carbohydrate metabolism in the endotoxic rats.

Animals↗
PubMed1983

Direct induction of tissue factor synthesis by endotoxin in human macrophages from diverse anatomical sites.

On exposure to endotoxin and other stimuli, human peripheral-blood mononuclear cells generate a potent procoagulant activity (PCA), identified as tissue factor. Although it is now recognized that the monocytes are the source of PCA, the question whether these cells per se are capable of procoagulant response to endotoxin or require lymphocyte collaboration remains unsettled. We have investigated the capacity of highly purified human macrophages from diverse anatomical sites to generate PCA following endotoxin stimulation. Purified (greater than 99%) monocyte-derived macrophages were obtained by prolonged (3-10 days) in-vitro culture of adherent monocytes using medium supplemented with 50% human serum. Purified (greater than 95%) peritoneal and milk macrophages were isolated by adherence to plastic. PCA was measured before and after incubation (4 hr at 37 degrees) with endotoxin (Salmonella enteritidis LPS, W or Escherichia coli O111:B4LPS, W, 1 microgram/ml final concentration) using a one-stage clotting assay and/or a two-stage amidolytic assay. Monocyte-derived macrophages had low baseline PCA (14-19 units/10(5) cells) but, upon exposure to endotoxin, displayed an eight-fold increase in PCA over control. Peritoneal and milk macrophages expressed very low baseline activity (1-5 units/10(5) cells). The latter, however, increased 15-20 times over control following endotoxin stimulation. PCA was identified as tissue factor by biological and immunological criteria. Its generation was completely abolished by cycloheximide. It is concluded that in the human mononuclear phagocyte series the capacity to produce PCA is not restricted to circulating monocytes but is also expressed by macrophages obtained from diverse anatomical sites. These macrophages appear to be autonomous in their procoagulant response to endotoxin.

Ascitic Fluid↗
PubMed1983

Utilization of fodder yeast and agro-industrial by-products in production of spores and biologically - active endotoxins from Bacillus thuringiensis.

A number of newly-devised fermentation media were evaluated with respect to their ability to support sporulation and biosynthesis of endotoxins by strains of Bacillus thuringiensis that are biologically active against Spodoptera littoralis, Heliothis armigera, and Spodoptera exigua. Fodder yeast from dried cells of Saccharomyces cerevisiae could be used as a complete mono-component medium for production of highly active spore-delta-endotoxin complexes from B. thur., vars. entomocidus, kurstaki and galleriae. Highest sporulation titers were obtained at 2% fodder yeast concentration with endotoxin yields ranging between 7 to 9 grams per liter of medium. Ground horse beans and kidney bean seeds could also be used successfully as complete media for sporulation and endotoxin production. Extracts of potato tubers and sweet potato roots were efficient media for active endotoxin production from B. thur. var. kurstaki, although the obtained yields were much lower than those produced in fodder yeast media. The utilization of fish meal, cotton seed meal, and residues of chicken from the slaughter-house as media for the production of endotoxins active against Spodoptera littoralis, was not successful. On the other hand, minced citrus peels, ground seeds of dates, and wheat bran could be successfully used in combination with fodder yeast as media for production of endotoxins, active against Heliothis armigera and Spodoptera exigua. Re-utilization of culture supernatants in a second fermentation cycle after supplementation with some nutrients gave promising results with some of the strains tested. The data obtained are discussed in view of their feasibility of application.

Bacillus thuringiensis↗
PubMed1983

[Quantitative endotoxin determination. Automated kinetic Limulus amebocyte lysate microtiter test with measurement of sample-related interferences].

A turbidometric, automated limulus amoebocyte lysate (LAL) microtiter test has been developed based on the evaluation of the LAL-endotoxin reaction kinetics. The maximal increase in optical density of each reaction mixture within 1 min is recorded. With this method an endotoxin standard curve is achieved which is linear over a concentration range of six decades. With presently available LAL methods sample-related inhibition or enhancement of the LAL endotoxin reaction may be overlooked and lead to false results. The quality of interfering factors can be characterized with our methods by spiking serial dilutions of the sample with constant endotoxin concentrations. The additional introduction of an internal standardization in our system allows the determination of endotoxin with simultaneous detection of quality and quantity of sample-induced interference. This procedure is based on a mathematic model which describes interference-caused alterations of the reaction revealed by addition of endotoxin in increasing concentrations. In comparison to the LAL tube test and the turbidometric determination at a given time the advantages of the developed method are demonstrated using three different samples (gelatin solution, adenine-HCl solution and a concentrate of coagulation factors (PPSB)). These are paradigmaticly selected because and enhancement of the LAL endotoxin reaction.

Animals↗
PubMed1980

Release of endotoxin from Neisseria meningitidis. A short survey with a preliminary report on virulence in mice.

Gram-negative bacteria release various amounts of cell wall fragments containing endotoxin into the surroundings. The authors demonstrated that liberation of endotoxin from Neisseria meningitidis during growth varied with strain and growth conditions and was dependent on whether the strains released large quantities of cell wall fragments into the medium or not. The ability to liberate endotoxin could be lost upon subcultivation and was associated with certain traits. The experiments indicated that short-lasting therapy with a penicillin dose big enough to give a rapid bactericidal effect increased the release of free, filtrable endotoxin from endotoxin liberating meningococci, but not from a non-liberating variant. This effect was not found when the meningococci were treated with chloramphenicol. The endotoxin liberating meningococcal strains were more virulent for mice than the non-liberating variants, indicating that the tendency to liberate cell wall fragments containing endotoxin may be a factor in the pathogenesis of meningococcal disease in mice.

Animals↗
PubMed1983

Distribution of radiolabeled endotoxin with particular reference to the eye: concise communication.

A single systemic injection of endotoxin (lipopolysaccharide or LPS) reproducibly induces a cellular infiltrate in the uveal tract of the rat eye within 24 hr. Other organs are not comparably sensitive to systemic endotoxin. One hypothesis to explain this unique sensitivity is that endotoxin is preferentially bound by ocular tissue. We tested this hypothesis by studying the distribution in the rat of intravenously injected endotoxin that had been radiolabeled with Tc-99m or P-32. With either radionuclide the concentration of endotoxin per gram of tissue at a variety of times after injection ranging from 5 min to 3 hr and 45 min, was markedly less in the eye than in liver, kidney, or spleen. A study with radiolabeled albumin indicated that these differences could not be ascribed solely to the organ's blood volume. They demonstrate, therefore, that the eye does not preferentially bind endotoxin, and they are compatible with the hypothesis that endotoxin's ocular effects are indirectly mediated.

Animals↗
PubMed1982

Effects of continuous intravenous infusion of Escherichia coli endotoxin into swine.

Escherichia coli endotoxin was continuously infused IV into 31 pigs. The response was related to the infusion rate. Of 13 pigs given endotoxin at the rate of 15.4 and 23.1 micrograms/kg of body weight/hour, 10 had bilateral renal cortical necrosis similar to a generalized Shwartzman lesion. All 13 pigs given endotoxin at the rate of 6.6 to 12.1 micrograms/kg/hour survived the infusion and were euthanatized 7 to 12 days later. Most of the pigs that developed chronic neurologic disturbances were given the smaller dose of endotoxin. Of 5 pigs given endotoxin at the rate of 22.0 to 23.1 micrograms/kg/hour after receiving 200 U of sodium heparin/kg of body weight, 1 died during the 48-hour period of infusion and the 4 pigs euthanatized 8 to 12 days later had lesions that were similar to those produced by endotoxin without heparin. The 4 control pigs given continuous IV infusion of isotonic saline solution at a rate of 30 dl/hour had no clinical signs or pathologic lesions. The continuous IV infusion of endotoxin into pigs at various doses produced similar clinical signs of endotoxic shock. Pigs that died acutely had widespread thrombosis. The hematologic findings indicated an intravascular coagulopathy and some of the clinical signs and lesions in the pigs resembled changes in the CNS in pigs with spontaneous edema disease (ED); however, distinct differences were also observed. Fibrinoid vascular necrosis did not occur in the CNS, and this lesion is consistently present in naturally occurring ED. The exact nature of the causal substance or substances causing ED is still unknown, but is considered an angiotoxin associated with hemolytic E coli.

Animals↗
PubMed1981

[Endotoxins in bacterial peritonitis].

Tests for the presence of endotoxin in blood and peritoneal fluid were performed at short intervals in 19 patients with peritonitis, 9 following gastric perforation, and 10 with perforation of the large bowel. A highly sensitive precipitation technique (LAL test) was used. Endotoxin was demonstrated in peritoneal fluid during the early stage of peritonitis in 15 of 19 patients (79%), while blood determination revealed endotoxin in 7 of 19 cases within the first 48 h. During the clinical course circulating endotoxin was recovered in 12 of 19 patients, which implies endotoxinemia in 63% of the cases. The prognostic significance of endotoxin determinations was high, since circulating endotoxin was demonstrated within the first 72 h in 8 of 9 patients with a fatal course. Demonstration of circulating endotoxin is a time-consuming and complicated procedure with great clinical significance in patients with gram-negative peritonitis.

Adult↗
PubMed1981

Evidence for an early lipid soluble cardiodepressant factor in rat serum after a sublethal dose of endotoxin.

The administration of a sublethal dose of E coli endotoxin (2 mg/kg) has been found to induce in the intact rat a slight decrease in mean carotid arterial pressure only 16 hours later. No death occurred whereas the same dose injected in the adrenalectomized rat caused lethality, and so did the higher dose (3 mg/kg) in the intact rat. Sera sampled two, four and 16 hours after administration of endotoxin (2 mg/kg) depressed contractile activity and the chronotropic response of isoproterenol in cultured rat heart cells. Such properties were not noted with sera sampled one or 24 hours after endotoxin administration. These cardiodepressant effects were localized in the lipid soluble fraction of endotoxin serum and absent in the fat-free portion. And yet neither endotoxin nor nonesterified fatty acid (NEFA) serum fraction was involved, since they did not alter cell culture activity. Moreover, though total or individual NEFA levels in endotoxic serum were higher than those of control rat serum four hours after endotoxin injection, they were not significantly different from control 16 hours later. It is concluded that the administration of a sublethal dose of endotoxin to the intact rat induces early and prolonged (up to 14-16 hours) release of one or more humoral lipid soluble cardiodepressant factor(s), even in the absence of systemic hypotension.

Adrenalectomy↗
PubMed1981

Endotoxin-induced lung injury in unanesthetized sheep: effect of methylprednisolone.

Our purpose was to study the effect of methylprednisolone (MPS) on endotoxin-induced lung injury. We used lung lymph flow and lymph protein content at sensitive indicators of pulmonary microvascular integrity in unanesthetized sheep. Seven animals were given E coli endotoxin (2 micrograms/kg) alone and also endotoxin with MPS pretreatment (30 mg/kg) in paired separate studies. The endotoxin injury was divided into an early hypertensive phase (30-90 minutes) characterized by a significant increase in pulmonary artery pressure (Ppa) and lymph flow, QL. This was followed later (3-5 hours) by a significant increase in protein-rich QL with normal pressures. MPS pretreatment significantly increased both injury phases in all animals. White cell count decreased in both groups; however, lymph beta-glucuronidase increased only in the nontreated group. Platelet count decreased in the nontreated group. Seven animals were then compared using endotoxin alone or with MPS treatment one hour after endotoxin. Only four of seven animals had a decrease in the lung injury after MPS treatment. We conclude that methylprednisolone is very effective in preventing lung injury, but only minimally effective in reversing the injury from endotoxin.

Animals↗