scholarly journals STUDIES ON THE GENERALIZED SHWARTZMAN REACTION

1955 ◽  
Vol 102 (3) ◽  
pp. 249-261 ◽  
Author(s):  
Lewis Thomas ◽  
Joel Brunson ◽  
Richard T. Smith
Keyword(s):  
Polyvinyl Alcohol ◽  
Intravenous Injection ◽  
Dextran Sulfate ◽  
Nitrogen Mustard ◽  
Protective Action ◽  
Gram Negative ◽  
Single Intravenous Injection ◽  
Intravenous Injections ◽  
Shwartzman Reaction

Lesions indistinguishable from those of the generalized Shwartzman reaction occured in rabbits when a single intravenous injection of Gram-negative bacterial endotoxin was accompanied, or followed, by an injection of one of the following synthetic, heparin-like, acidic polymers-sodium polyanethol sulfonate, dextran sulfate, or sodium polyvinyl alcohol sulfonate. These reactions were produced by doses of polymer or of endotoxin which were without demonstrable effect when given singly. Heparin, in those similar to those previously shown to protect rabbits against the lesions of the generalized Shwartzman reaction, prevented the reaction to the combined injection of endotoxin and acidic polymers. Nitrogen mustard, which was previously shown to prevent the lesions of the generalized Shwartzman reaction from occurring after two intravenous injections of endotoxin, had no protective action against the lesions produced by the combined injection of endotoxin and polymer. Cortisone did not affect the reaction to endotoxin and polymer. The role of fibrinogen in the reaction under study is discussed in the paper which follows.

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 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 The role of granulocytes in the activation of intravascular coagulation and the precipitation of soluble fibrin by endotoxin

Blood ◽  
1975 ◽  
Vol 45 (5) ◽  
pp. 631-641 ◽  
Author(s):  
G Muller-Berghaus ◽  
T Eckhardt
Keyword(s):  
Nitrogen Mustard ◽  
Endotoxin Administration ◽  
Soluble Fibrin ◽  
Intravascular Coagulation ◽  
Platelet Counts ◽  
Intravenous Injections

Abstract This study examines the role of neutrophils (PMN) in the pathogenesis of endotoxin-induced microclot formation. It is intended to clarify whether granulocytes are involved in endotoxin-induced activation of intravascular coagulation (generation of soluble fibrin) and/or in endotoxin-induced precipitation of soluble fibrin. Precipitation of soluble fibrin was achieved by injection of endotoxin into ancrod- infused rabbits with circulating soluble fibrin (first model). Activation of intravascular coagulation was elicited by two intravenous injections of endotoxin into rabbits (second model). Seventy-two and ninety-six hours after injection of nitrogen mustard, leukopenic rabbits had PMN counts between 0 and 50 cells per mul. Neutropenia did not prevent the occurrence of glomerular microclots after infusion of ancrod and injection of endotoxin (first model). Neutropenia influenced neither the decrease in mean fibrinogen concentrations nor the drop in mean platelet counts after ancrod and endotoxin administration. In contrast to the first model, neutropenia prevented the occurrence of glomerular microclots and of circulating soluble fibrin after two injections of endotoxin (second model). It did not, however, protect rabbits from the decrease in mean platelet counts after endotoxin administration. These data indicate that granulocytes are involved in endotoxin-induced activation of intravascular coagulation and the production of soluble fibrin but are not essential to endotoxin-induced precipitation of soluble fibrin.

scholarly journals The role of granulocytes in the activation of intravascular coagulation and the precipitation of soluble fibrin by endotoxin

Blood ◽  
1975 ◽  
Vol 45 (5) ◽  
pp. 631-641
Author(s):  
G Muller-Berghaus ◽  
T Eckhardt
Keyword(s):  
Nitrogen Mustard ◽  
Endotoxin Administration ◽  
Soluble Fibrin ◽  
Intravascular Coagulation ◽  
Platelet Counts ◽  
Intravenous Injections

This study examines the role of neutrophils (PMN) in the pathogenesis of endotoxin-induced microclot formation. It is intended to clarify whether granulocytes are involved in endotoxin-induced activation of intravascular coagulation (generation of soluble fibrin) and/or in endotoxin-induced precipitation of soluble fibrin. Precipitation of soluble fibrin was achieved by injection of endotoxin into ancrod- infused rabbits with circulating soluble fibrin (first model). Activation of intravascular coagulation was elicited by two intravenous injections of endotoxin into rabbits (second model). Seventy-two and ninety-six hours after injection of nitrogen mustard, leukopenic rabbits had PMN counts between 0 and 50 cells per mul. Neutropenia did not prevent the occurrence of glomerular microclots after infusion of ancrod and injection of endotoxin (first model). Neutropenia influenced neither the decrease in mean fibrinogen concentrations nor the drop in mean platelet counts after ancrod and endotoxin administration. In contrast to the first model, neutropenia prevented the occurrence of glomerular microclots and of circulating soluble fibrin after two injections of endotoxin (second model). It did not, however, protect rabbits from the decrease in mean platelet counts after endotoxin administration. These data indicate that granulocytes are involved in endotoxin-induced activation of intravascular coagulation and the production of soluble fibrin but are not essential to endotoxin-induced precipitation of soluble fibrin.

scholarly journals THE ROLE OF VASOCONSTRICTION IN THE LOCAL SHWARTZMAN REACTION

1957 ◽  
Vol 105 (6) ◽  
pp. 643-652 ◽  
Author(s):  
David P. Rall ◽  
Margaret G. Kelly
Keyword(s):  
Nitrogen Mustard ◽  
Lactic Acid Production ◽  
Metabolic Changes ◽  
Bacterial Polysaccharide ◽  
Specific Sequence ◽  
Abdominal Skin ◽  
Shwartzman Reaction ◽  
Adrenergic Blocking ◽  
Local Shwartzman Reaction

The local Shwartzman reaction was provoked in the skin of the ear, hind leg, and costovertebral angle of the rabbit, as well as in the ventral abdominal skin. Certain adrenergic blocking drugs reduced the incidence of positive reactions when given prior to the provocative dose of bacterial polysaccharide. Epinephrine and other vasoconstrictor drugs administered intradermally into the prepared skin site produced typical hemorrhagic-necrotic lesions when the usual intravenous injection of polysaccharide was omitted. This reaction could be blocked by adrenergic blocking drugs, but appeared to be augmented by heparin or nitrogen mustard. A hypothesis has been developed to help explain the mechanism of the local Shwartzman reaction. Following the preparatory dose, tissue metabolic changes occur which lead to increased lactic acid production and render the area particularly susceptible to anoxia. Following the provocative dose, adrenergic vasoconstriction occurs. It is suggested that this vasoconstriction may be intensified at the prepared site by small residual amounts of the preparatory dose of polysaccharide which might potentiate the action of the epinephrine. The anoxia initiated by the vasoconstriction is prolonged and intensified by the formation of intravascular thrombi around clumps of leucocytes and platelets. This anoxia, superimposed on the local metabolic changes, leads to the characteristic lesion of hemorrhage and necrosis. Thus a combination of factors, all of causal importance and largely due to known pharmacologic properties of bacterial lipopolysaccharide, occur in specific sequence to lead to the classic local 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.

Studies on the Pathogenesis of the Generalized Shwartzman Reaction

1964 ◽  
Vol 12 (02) ◽  
pp. 452-461 ◽  
Author(s):  
F Rodríguez-Erdmann
Keyword(s):  
Intravenous Injection ◽  
Coagulation System ◽  
Single Intravenous Injection ◽  
E Coli ◽  
Haemorrhagic Diathesis ◽  
Shwartzman Reaction ◽  
Plasma Factors

SummaryThe generalized Shwartzman reaction (gSr) was produced in pregnant rabbits by means of a single intravenous injection of E.-coli endotoxin. The animals developed a profound and a haemorrhagic diathesis. The haemorrhagic condition is thought to be the result of an acute consumption of the plasma-factors of the coagulation system. The pathogenesis of the gSr is discussed in the light of literature dealing with this phenomenon.

scholarly journals STUDIES ON THE PATHOGENESIS OF FEVER

1957 ◽  
Vol 106 (6) ◽  
pp. 787-809 ◽  
Author(s):  
Robert G. Petersdorf ◽  
Willis R. Keene ◽  
Ivan L. Bennett
Keyword(s):  
Intravenous Injection ◽  
Bacterial Endotoxin ◽  
Endogenous Pyrogen ◽  
Febrile Response ◽  
Single Intravenous Injection ◽  
Shwartzman Reaction ◽  
Endogenous Serum Pyrogen ◽  
Indirect Action ◽  
Local Shwartzman Reaction ◽  
Bacterial Products

The "endogenous serum pyrogen" that appears in the circulating blood after a single intravenous injection of endotoxin does not produce leukopenia in normal animals, fails to provoke the local Shwartzman reaction, and elicits no "tolerance" when injected daily. Suppression of the febrile response to endotoxin by prednisone does not prevent the appearance of pyrogen in the blood. Animals given large amounts of endotoxin daily continue to respond with high fevers despite failure of endogenous serum pyrogen to appear in detectable amounts after the first two or three injections. Analysis of the response to daily injections shows clearly that the fever during the first 2 hours after administration of endotoxin is unrelated to levels of endogenous serum pyrogen; in contrast, the magnitude of the fever after the 2nd hour correlates well with endogenous pyrogen in some instances. The leukopenic response to endotoxin could not be correlated with the appearance of endogenous serum pyrogen. The differences between endotoxin and endogenous pyrogen and the similarities between leukocyte extracts (sterile exudates) and endogenous pyrogen are summarized and discussed. Dissociation of the febrile response to bacterial endotoxin and levels of endogenous serum pyrogen are discussed and it is concluded that a mechanism involving both direct and indirect action of endotoxins offers the best explanation for the pyrogenic action of these bacterial products.

The Role of Platelets and Leukocytes in Endotoxin-Induced Disseminated Intravascular Coagulation (DIC)

1975 ◽  
Author(s):  
V. Gurewich ◽  
B. Lipinski
Keyword(s):  
Nitrogen Mustard ◽  
Fibrin Deposition ◽  
Platelet Factor ◽  
Cortical Necrosis ◽  
Gram Negative ◽  
Renal Cortical Necrosis ◽  
Heparin Activity ◽  
Wbc Count ◽  
Substantial Drop

DIC was induced by two appropriately spaced injections of endotoxin. Evidence of fibrin deposition was determined by a previously described radioactive technique, by autoradiography of kidney slices and by the development of renal cortical necrosis. In animals made leukopenic but not thrombocytopenic by nitrogen mustard, fibrin deposition was inhibited. The degree of inhibition appeared proportional to the degree of leukopenia. Another group of rabbits was made thrombocytopenic but not leukopenic by the injection of neuraminidase (Sigma) 48 hours before the first dose of endotoxin. Thrombocytopenia (< 50,000/mm3) failed to inhibit fibrin deposition and the development of renal cortical necrosis. These animals showed the characteristic biphasic white cell response and an increase in plasma anti-heparin activity. Comparable findings were observed in a patient with DIC secondary to gram negative septicemia. In this patient, a substantial drop in WBC count developed (8.500-900/mm3). Platelet factor 4 determined by an immunoassay (Dr. S. Niewiarowski) was normal. It is concluded that granulocytes but not platelets are essential for endotoxin-induced DIC. It is likely that the increase in anti-heparin activity previously described is derived from white cells and not platelets.

scholarly journals STUDIES ON THE GENERALIZED SHWARTZMAN REACTION

1955 ◽  
Vol 102 (3) ◽  
pp. 263-278 ◽  
Author(s):  
Lewis Thomas ◽  
Richard T. Smith ◽  
Richard von Korff
Keyword(s):  
Low Temperature ◽  
Intravenous Injection ◽  
Nitrogen Mustard ◽  
Molecular Size ◽  
Qualitative Change ◽  
Synthetic Polymer ◽  
Shwartzman Reaction ◽  
Synthetic Acid

An intravenous injection of sodium polyanethol sulfonate, a heparin-like synthetic polymer of large molecular size, into rabbits given endotoxin 2 hours previously, results in the abrupt disappearance from the circulating blood of a large proportion of fibrinogen. The depletion of circulating fibrinogen is prevented by the administration of heparin prior to the synthetic polymer. In animals receiving the polymer alone, or endotoxin alone, no depletion of fibrinogen occurs. It is suggested that the intravascular deposition of fibrinoid and the subsequent necrotizing lesions of the generalized Shwartzman reaction, which occur after the combined injection of endotoxin and synthetic acid polymer, may be due to the intravascular precipitation of fibrinogen by polymer. A qualitative change in fibrinogen, characterized by its precipitability by heparin at low temperature, is regularly demonstrable in plasma between 1 and 4 hours after an intravenous injection of endotoxin. The appearance of this heparin-precipitable fraction is prevented by treatment with heparin before endotoxin. It is not influenced by nitrogen mustard or cortisone. During the period when depletion of circulating fibrinogen is produced by polyanethol, in endotoxin-treated animals, the heparin-precipitable fraction also disappears from the blood. It is suggested that the change in fibrinogen may represent partial polymertization, and the cold precipitability of this material by heparin may be related to its enhanced precipitability, in vivo, by polyanethol. An hypothesis which accounts for certain events in the generalized Shwartzman reaction, based on observations reported in this study, is presented.

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