scholarly journals STUDIES ON THE GENERALIZED SHWARTZMAN REACTION

1953 ◽  
Vol 97 (6) ◽  
pp. 871-888 ◽  
Author(s):  
Robert A. Good ◽  
Lewis Thomas
Keyword(s):  
Intravenous Injection ◽  
Essential Role ◽  
Vascular Occlusion ◽  
Lethal Effect ◽  
Intradermal Injection ◽  
Cortical Necrosis ◽  
Hemorrhagic Necrosis ◽  
Shwartzman Reaction ◽  
Previously Treated ◽  
Glomerular Capillaries

In order to explore the hypothesis that the occurrence of thrombosis of small blood vessels is an essential stage in the development of the local and generalized Shwartzman reactions, the effect of heparin was studied. Aqueous heparin, administered intravenously, and "depot" heparin, injected subcutaneously, prevented completely the occurrence of the local and generalized Shwartzman phenomena. The amounts of heparin required for protection were similar to the amounts required to produce sustained incoagulability of the blood of rabbits for a period of at least 4 hours. The local and generalized Shwartzman reactions were prevented when heparin was given at the time of provocation, but not when heparin was administered during the period of preparation. Heparin prevented the development of bilateral cortical necrosis of the kidneys following a single intravenous injection of meningococcal toxin in rabbits previously treated with cortisone or thorotrast. Hemorrhagic necrosis of the skin which follows an intradermal injection of toxin in thorotrast-treated rabbits was also prevented by heparin. Provocation of the dermal Shwartzman reaction with glycogen, saline suspension of rabbit liver, and human serum was prevented by treatment with heparin. Heparin itself, in the preparations and dosages used, had no consistent effect on either white blood cell or platelet counts. Heparin had no effect on the occurrence of polymorphonuclear leukopenia which follows an intravenous injection of meningococcal toxin. Treatment with heparin did not interfere with the lethal effect of single, large doses of meningococcus toxin. In animals in which bilateral cortical necrosis of the kidneys was prevented by heparin, occlusion of the glomerular capillaries by "fibrinoid" material did not occur. These observations support the concept that vascular occlusion plays an essential role in the development of the local and generalized Shwartzman reactions.

scholarly journals STUDIES ON THE GENERALIZED SHWARTZMAN REACTION

1952 ◽  
Vol 96 (6) ◽  
pp. 625-641 ◽  
Author(s):  
Robert A. Good ◽  
Lewis Thomas
Keyword(s):  
Intravenous Injection ◽  
Trypan Blue ◽  
Nitrogen Mustard ◽  
Skin Lesions ◽  
Intradermal Injection ◽  
Cortical Necrosis ◽  
Single Intravenous Injection ◽  
Shwartzman Reaction ◽  
Kidney Lesions ◽  
Local Shwartzman Reaction

Intravenous injection of thorotrast or trypan blue rendered rabbits susceptible to the production of bilateral cortical necrosis of the kidneys by a single intravenous injection of small amounts of meningococcal or Serratia marcescens toxin. This reaction was not produced when thorotrast or trypan blue were injected after toxin had been given. A single intradermal injection of toxin produced hemorrhagic skin lesions resembling the local Shwartzman reaction in rabbits given thorotrast 6 hours previously. These animals also developed bilateral cortical necrosis of the kidneys. When the order of injection was reversed, and thorotrast given after toxin, neither skin nor kidney lesions occurred. The skin and kidney lesions in thorotrast-treated rabbits were, like the local and generalized Shwartzman reactions, completely prevented by treatment with nitrogen mustard, in doses sufficient to produce polymorphonuclear leukopenia. The significance of these reactions, and their relationship to the previously described response to toxin in cortisone-treated rabbits, are discussed.

scholarly journals THE EFFECT OF CORTISONE ON THE SHWARTZMAN REACTION

1952 ◽  
Vol 95 (4) ◽  
pp. 409-428 ◽  
Author(s):  
Lewis Thomas ◽  
Robert A. Good ◽  
Keyword(s):  
Nitrogen Mustard ◽  
Intradermal Injection ◽  
Renal Lesion ◽  
Cortical Necrosis ◽  
Intravenous Injections ◽  
Pretreatment Period ◽  
Shwartzman Reaction ◽  
Systemic Symptoms ◽  
Schiff Reaction ◽  
Glomerular Capillaries

1. Cortisone, in a dose of 25 mg. daily and with a pretreatment period of 3 days, in rabbits weighing 1 to 1.5 kilos, did not inhibit the dermal Shwartzman reaction produced by meningococcal or S. marcescens toxin. 2. In cortisone-treated rabbits, a single intradermal injection of toxin produced a primary reaction of hemorrhage and necrosis in the skin at the injected site. This lesion resembled the Shwartzman reaction in its gross and histological appearance. 3. Like the Shwartzman reaction, the primary hemorrhagic reaction in cortisone-treated rabbits was prevented by nitrogen mustard, and the preventive effect of nitrogen mustard was partly eliminated when the femoral marrow was protected against the latter agent. 4. A single intravenous injection of meningococcal or S. marcescens toxin, in cortisone-treated rabbits, was followed by bilateral cortical necrosis of the kidneys in the majority of instances. The renal lesions, as well as hemorrhages in the lungs, spleen, liver, and gastrointestinal tract, resembled the lesions of the generalized Shwartzman reaction. Histologically, the glomerular capillaries in both types appeared to be occluded by homogeneous, eosinophilic material which showed a strongly positive Schiff reaction. 5. The renal lesion following a single injection of toxin in cortisone-treated animals, and that following two intravenous injections in the generalized Shwartzman reaction, were both completely prevented by nitrogen mustard. This effect of nitrogen mustard was inhibited when the femoral marrow was protected against the latter agent. 6. The injection of S. marcescens toxin into the skin of normal rabbits did not cause systemic symptoms, nor was it possible to provoke the generalized Shwartzman reaction by this route. In cortisone-treated rabbits, a similar intradermal injection was regularly followed by the development of bilateral cortical necrosis of the kidneys, indicating that absorption of toxin from the skin occurred in these animals. 7. Possible mechanisms to account for the observations are discussed. The authors are obliged to Professor James R. Dawson for many helpful suggestions during the course of this investigation.

scholarly journals STRAIN DIFFERENCES IN LOCAL HEMORRHAGIC RESPONSE (SHWARTZMAN-LIKE REACTION) OF MICE TO A SINGLE INTRADERMAL INJECTION OF BACTERIAL POLYSACCHARIDES

1957 ◽  
Vol 105 (6) ◽  
pp. 653-664 ◽  
Author(s):  
Margaret G. Kelly ◽  
Norman H. Smith ◽  
Isidore Wodinsky ◽  
David P. Rall
Keyword(s):  
Strain Differences ◽  
Inbred Strains ◽  
Blocking Agent ◽  
Intradermal Injection ◽  
F1 Hybrid ◽  
Hemorrhagic Necrosis ◽  
Inbred Strains Of Mice ◽  
Anticoagulant Drug ◽  
Shwartzman Reaction ◽  
Hemorrhagic Lesion

A survey of inbred strains of mice was made to determine whether the phenomenon of dermal hemorrhagic necrosis, as described in rabbits by Shwartzman, could be elicited in mice by bacterial polysaccharide preparations of demonstrated activity in rabbits. The polysaccharide preparations used were obtained from cultures of S. marcescens, S. typhosa, Ps. aeruginosa, and H. pertussis. Ten of the strains tested were unreactive. Three strains of mice and one F1 hybrid subline developed a hemorrhagic lesion at the site of injection of a single, relatively high intradermal dose of polysaccharide. Some increase in incidence of hemorrhagic lesions was obtained when the intradermal dose was followed in 24 hours by an intravenous injection. In the gross and microscopically, the skin lesion produced in mice resembled the Shwartzman reaction in rabbits. An adrenergic blocking agent, SY-28, and an anticoagulant drug, coumadin, both of which block the dermal Shwartzman reaction in rabbits, also blocked the hemorrhagic skin reaction in mice.

scholarly journals STUDIES ON THE GENERALIZED SHWARTZMAN REACTION

1952 ◽  
Vol 96 (6) ◽  
pp. 605-624 ◽  
Author(s):  
Lewis Thomas ◽  
Robert A. Good
Keyword(s):  
Nitrogen Mustard ◽  
Lethal Effect ◽  
Optimal Time ◽  
Time Interval ◽  
Renal Lesion ◽  
Protein Nitrogen ◽  
Local Skin ◽  
Cortical Necrosis ◽  
Before And After ◽  
Shwartzman Reaction

Certain factors involved in the production of the generalized Shwartzman reaction with meningococcal toxin in rabbits were investigated. The optimal amounts of toxin for the preparing and provoking injections, and the optimal time interval between injections were determined. Under suitable conditions of dosage and timing, bilateral cortical necrosis of the kidneys was produced in a high proportion of animals. When excessive amounts of toxin were used for preparation the incidence of the reaction was reduced. Animals undergoing the generalized Shwartzman reaction became severely prostrated within several hours after the provoking injection of toxin. The renal lesion became fully developed within 24 hours, and its occurrence was associated with a rise of the blood non-protein nitrogen. Edema and petechial hemorrhages in the ears were observed in rabbits with advanced renal lesions. The earliest change in the kidneys in the generalized Shwartzman reaction was the appearance of homogeneous, eosinophilic material, resembling fibrinoid, within the lumen of the glomerular capillaries. Occlusion of the capillaries by this material was regarded as the cause of subsequent tubular necrosis in the renal cortex. The material appeared to be derived from the blood, rather than from the capillary walls. Cortisone enhanced the lethal effect of a single, large dose of meningococcal toxin, as well as causing bilateral renal cortical necrosis. The generalized Shwartzman reaction produced by two injections of toxin was aggravated by cortisone and ACTH. Profound polymorphonuclear leukopenia was produced by both the preparing and provoking injections of toxin. When leukopenia was produced before the preparing injection of toxin, by treatment with nitrogen mustard, the generalized Shwartzman reaction was inhibited. During the intervals before and after leukopenia, and when leukopenia was prevented by shielding the femoral bone marrow from the action of nitrogen mustard, no inhibition of the generalized Shwartzman phenomenon was demonstrable. Various colloidal and particulate materials, which are capable of provoking the local skin Shwartzman reaction when injected intravenously, failed to provoke the generalized Shwartzman reaction. A working hypothesis was set up to account for certain events in the generalized Shwartzman reaction.

scholarly journals EXPERIMENTAL PRODUCTION OF HEMORRHAGE AND VASCULAR LESIONS IN LYMPH NODES: AN EXTENSION OF THE SHWARTZMAN PHENOMENON

1937 ◽  
Vol 65 (2) ◽  
pp. 287-302 ◽  
Author(s):  
Lewis Henry Koplik
Keyword(s):  
Lymph Nodes ◽  
Intravenous Injection ◽  
Lymphatic Drainage ◽  
Intradermal Injection ◽  
Vascular Lesions ◽  
Experimental Production ◽  
Intravenous Injections ◽  
Shwartzman Reaction ◽  
High Concentrations ◽  
Shwartzman Phenomenon

Characteristic changes are produced in the lymph nodes of rabbits following the intravenous injection of certain bacterial filtrates administered 24 hours after either an intralymphatic or an intradermal injection of the same filtrate. These changes are limited to the nodes served by the lymphatic injected or to those furnishing the lymphatic drainage for the injected skin site. By either method the initial or preparatory injection of filtrate reaches the lymph nodes through one or more of its afferent lymphatics, and similar lesions are produced in the nodes. The lesions consist of hemorrhages recognizable by gross and microscopic examination. The capillaries and veins are congested and thrombosed. Their endothelial cells are swollen. Arterioles are generally little affected. Though hemorrhages and thromboses are usually seen together in the nodes, they have been observed occurring independently. They are both probably secondary to endothelial changes. The lesions are not dependent on the amount of preexisting inflammation in the nodes. Endothelial changes, hemorrhages and thromboses were usually noted in the regional nodes when positive Shwartzman reactions had been elicited in prepared skin by intravenous injection of the bacterial filtrate. However, these lesions in many instances were observed under similar conditions in these nodes even when the Shwartzman reaction in the skin was negative. It appears that lymph nodes are more susceptible to the production of the Shwartzman phenomenon than the skin sites which they drain. A single intralymphatic or intradermal injection of the bacterial filtrates used in this study, even in high concentrations, does not produce in adjacent lymph nodes the characteristic changes noted when this preparatory injection is followed by a subsequent intravenous injection of the filtrate. Single intravenous injections also are not productive of hemorrhage and thrombosis in lymph nodes.

scholarly journals Intravascular Coagulation with Generalized Shwartzman Reaction Induced by a Heparin-Like Anticoagulant (Liquoid)

1967 ◽  
Vol 18 (01/02) ◽  
pp. 024-039 ◽  
Author(s):  
S. A Evensen ◽  
M Jeremic ◽  
P. F Hjort
Keyword(s):  
Body Weight ◽  
Intravenous Injection ◽  
Anticoagulant Effect ◽  
Coagulation System ◽  
Factor V ◽  
Cortical Necrosis ◽  
Renal Cortical Necrosis ◽  
Intravascular Coagulation ◽  
Shwartzman Reaction

SummaryLiquoid (sodium polyanethol sulfonate), a synthetic heparin-like anticoagulant, produces renal cortical necrosis in rabbits. This lesion is indistinguishable from the generalized Shwartzman reaction which is caused by intravascular coagulation in a prepared animal. We have investigated this apparently paradoxic effect of Liquoid. Our main findings are:1. Liquoid is a potent heparin-like anticoagulant. One mg of Liquoid is neutralized by 1 mg of Polybrene. After intravenous injection the anticoagulant effect is immediate and persists for several hours.2. In larger concentrations, Liquoid precipitates fibrinogen. The precipitation does not depend on an intact coagulation system; the precipitates are dissolved in 30% urea.3. An intravenous injection of 20 mg Liquoid/1500 g body-weight produces an early thrombocytopenia, a progressive depletion of fibrinogen and factor V, the appearance of cold-precipitating material in plasma, and severe renal cortical necrosis.4. Pretreatment with warfarin completely prevents all of these effects, except a moderate fall in platelets.We conclude that Liquoid produces these effects, not by precipitation of fibrinogen, but by intravascular coagulation, probably released through aggregation and damage of the platelets. Thus, intravascular coagulation is again confirmed as the final event in the generalized Shwartzman reaction.

Hageman Factor Activity in Liquoid-Induced Consumption Coagulopathy

1971 ◽  
Vol 26 (01) ◽  
pp. 058-070 ◽  
Author(s):  
G Müller-Berghaus ◽  
H. G Lasch
Keyword(s):  
Intravenous Injection ◽  
Coumarin Derivative ◽  
Consumption Coagulopathy ◽  
Factor Activity ◽  
Hageman Factor ◽  
Platelet Counts ◽  
Shwartzman Reaction ◽  
Initial Drop ◽  
Glomerular Capillaries

Summary1. Consumption coagulopathy was induced by intravenous injection of Liquoid (sodium polyanetholsulfonate) into rabbits. Thirteen out of 21 animals injected with Liquoid showed fibrin formation in the renal glomerular capillaries characteristic of the generalized Shwartzman reaction. In these 13 animals, a pronounced drop in Hageman factor activity was observed in addition to a decrease in platelet counts and fibrinogen levels.2. The consumption coagulopathy induced by Liquoid could be prevented by pretreatment of the rabbits with phenprocoumon, a coumarin derivative. None of 21 rabbits pretreated by this anticoagulant and injected with Liquoid showed fibrin in the renal glomerular capillaries. Phenprocoumon pretreatment did not influence the decrease in platelet counts, but it did significantly diminish the drop in fibrinogen levels. Although disseminated intra vascular coagulation and the generalized Shwartzman reaction could be inhibited by phenprocoumon pretreatment, this anticoagulant could not prevent the initial drop in Hageman factor activity after Liquoid injection.3. Phenprocoumon did not influence the activity or synthesis of Hageman factor. As phenprocoumon pretreatment could not prevent the drop in Hageman factor activity after intravenous injection of Liquoid, it might be concluded that the Hageman factor is either consumed, directly inactivated or destroyed in the animals independent of the presence of the prothrombin complex. These findings support earlier studies which have shown that inhibition of Hageman factor activation in vivo can prevent the generalized Shwartzman reaction induced by Liquoid.

scholarly journals ANTIGEN-ANTIBODY REACTION IN THE PATHOGENESIS OF BILATERAL RENAL CORTICAL NECROSIS

1963 ◽  
Vol 117 (3) ◽  
pp. 365-376 ◽  
Author(s):  
Leung Lee
Keyword(s):  
Immune Complexes ◽  
Coagulation System ◽  
Cortical Necrosis ◽  
Renal Cortical Necrosis ◽  
Bacterial Endotoxins ◽  
Shwartzman Reaction ◽  
Soluble Immune Complexes ◽  
Antigen Antibody ◽  
Glomerular Capillaries

In the presence of reticuloendothelial blockade, the intravenous injection of a protein antigen into specifically immunized rabbits or the infusion of soluble immune complexes into normal animals has been shown to result in the production of bilateral renal cortical necrosis. The similarity in the pathogenesis of this lesion and that seen in the classical generalized Shwartzman reaction produced by bacterial endotoxins is indicated by (a) the failure of both lesions to develop in animals pretreated with large doses of heparin, (b) by the finding of "heparin-precipitable fibrinogen" in the circulation, and (c) by the presence of massive fibrin deposits within the glomerular capillaries. These findings indicate that antigen-antibody reactions in vivo are capable of activating the blood coagulation system and that the mode of action of bacterial endotoxins may have an immunological basis.

scholarly journals THE ROLE OF EPINEPHRINE IN THE REACTIONS PRODUCED BY THE ENDOTOXINS OF GRAM-NEGATIVE BACTERIA

1956 ◽  
Vol 104 (6) ◽  
pp. 865-880 ◽  
Author(s):  
Lewis Thomas
Keyword(s):  
Blood Vessels ◽  
Intravenous Injection ◽  
Acute Inflammation ◽  
Nitrogen Mustard ◽  
Basic Mechanism ◽  
Intradermal Injection ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Hemorrhagic Necrosis

Extensive lesions of dermal hemorrhagic necrosis occurred in rabbits when epinephrine (or norepinephrine) was injected into the skin within 4 hours after an intravenous injection of endotoxin. As little as 5 µg. of intradermal epinephrine, and 1 µg. of intravenous endotoxin, were sufficient to produce lesions. Similar lesions, but smaller in size and surrounded by a zone of acute inflammation, were produced by intradermal injection of a mixture of comparable amounts of endotoxin and epinephrine. No lesions were produced by combinations of endotoxin with serotonin, pitressin, or ephedrine. Both types of epinephrine-endotoxin lesion were prevented by pretreatment with cortisone, dibenzyline, and chlorpromazine. They were not prevented by heparin or nitrogen mustard. The lesions produced by intradermal mixtures of epinephrine and endotoxin were greatly enhanced in size and severity in animals treated with nitrogen mustard. Both types of lesion were prevented in rabbits rendered "tolerant" by repeated injections of sublethal amounts of endotoxin. It is concluded that endotoxin has the property of altering the reactivity of blood vessels to epinephrine in such a way that this hormone becomes a potent necrotizing agent. The possibility that this effect may represent a basic mechanism in the various intoxicating actions of endotoxin, and certain implications of this hypothesis, are discussed.

scholarly journals STUDIES ON THE GENERALIZED SHWARTZMAN REACTION

1953 ◽  
Vol 97 (5) ◽  
pp. 751-766 ◽  
Author(s):  
Lewis Thomas ◽  
Floyd W. Denny ◽  
Joan Floyd
Keyword(s):  
Time Interval ◽  
Time Of Death ◽  
Fibrinoid Necrosis ◽  
Optimal Conditions ◽  
Cortical Necrosis ◽  
Intravenous Injections ◽  
Hemorrhagic Necrosis ◽  
Group A ◽  
Shwartzman Reaction ◽  
Systemic Infections

Cutaneous and systemic infections of rabbits by Group A streptococci bring about a state of preparation for, respectively, the local and generalized Shwartzman reactions, produced by intravenous injection of meningococcal or S. marcescens toxin. With maximal systemic streptococcal infections, the lesions of the generalized Shwartzman reaction do not differ from those caused by two successive intravenous injections of Gram-negative bacterial toxins. The characteristic lesions of the reaction are bilateral cortical necrosis of the kidneys, hemorrhagic necrosis in the lungs, liver, and spleen, and myofiber necrosis in the myocardium. Under optimal conditions involving the dosages of streptococci and toxin, and the time interval between the injections, a new lesion consisting of necrosis and the accumulation of fibrinoid material in the walls of the coronary arteries occurred in approximately 50 per cent of animals within 48 hours after the injection of meningococcal toxin. Fibrinoid necrosis was not observed in the arteries of tissues other than the heart. It did not occur in control rabbits injected with streptococci alone or toxin alone, nor in animals with the generalized Shwartzman reaction produced by two intravenous injections of toxin. Streptococcal bacteriemia was present at the time of death in one-third of the animals with fibrinoid necrosis. In one animal, a group of bodies resembling cocci in chains was seen within the wall of a coronary artery with fibrinoid necrosis. A series of photomicrographs to illustrate the pathological changes in the hearts and kidneys of streptococcus-infected rabbits subjected to the Shwartzman reaction is presented.

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