Physiologic Action of Clostridium Welchii (Type A) Toxins in Dogs 123

Zamecnik, Paul C.; Nathanson, Ira T.; Aub, Joseph C.

doi:10.1172/jci101821

Cited by 24 publications

(4 citation statements)

References 20 publications

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“…welchii toxic filtrates (14) have demonstrated that the dosage, rate, and route of administration of the toxins determine the type of effects on dogs. The same considerations apply to the present studies on Cl.…”

Section: Discussionmentioning

confidence: 99%

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Physiologic Action of Clostridium Oedematiens (Novyi) Toxin in Dogs 123

Aub¹,

Zamecnik²,

Nathanson³

1947

J. Clin. Invest.

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The frequent occurrence of Cl. oedematiens in war wounds in general and in gas gangrene in particular (1) has stimulated the study of the physiologic effects of the toxin of this organism. The availability of Cl. oedematiens toxin in purified form has made it possible to investigate its action as distinct from toxins of other synergistic and symbiotic organisms which contribute to the clinical picture of anaerobic infections. Such a study is herein reported.The pathologic effects of Cl. oedematiens were described first by Novy (2); and, subsequently, on the same or closely related organisms, by Weinberg and Seguin (3), and others (4 to 6). Previous studies of the physiologic effects of this toxin have not, however, reached our attention. It has not been demonstrated that more than one toxin is produced by the organism, although analogy with Cl. welchii makes this a possibility.Recent work from this laboratory (7 to 13) has shown that the presence of clostridia may constitute an important factor in some forms of traumatic shock produced experimentally in dogs. The present communication points out that a picture similar to that of traumatic shock may be produced experimentally in dogs by the injection of Cl. oedematiens toxin. MATERIALS AND METHODSThe experiments have been carried out using several preparations of purified Cl. oedematiens (Novyi) The methods used in this study have been described previously (14), with the following exceptions: liver function was tested by the bromsulfalein excretion method; and kidney function was tested by phenolsulfonphthalein excretion. RESULTS Cl. oedematiens intravenouslyDosage: Thirty-five dogs were injected intravenously with a dosage of toxin which ranged from 3,700 down to 20 MLD per kgm. Of 9 unanesthetized dogs simply injected with varying amounts of toxin and then observed, there was only 1 survivor, the animal receiving the 20 MLD per kgm. dose. Dogs given 46 and 90 MLD per kgm. died on the third day. With larger doses of toxin (over 500 MLD per kgm.) the survival time was uniformly shortened to a matter of hours.Twenty-six dogs were anesthetized and, following carotid and tracheal cannulation, were injected intravenously with toxin. The majority of these animals were given 1,250 MLD per kgm., and only 3 out of the 26 survived longer than 8 hours.Rate of injection: There was no great differ-. ence in the effect of the toxin whether it was given rapidly in small volume (less than 10 ml.) by syringe, or diluted to 100 ml. and allowed to drip into the animal by slow infusion over a period of hours. The survival time following slow infusion was an hour or two longer, and the decline of the blood pressure more gradual, but otherwise the picture was the same by either method.

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Section: Discussionmentioning

confidence: 99%

“…oedematiens (Novyi) The methods used in this study have been described previously (14), with the following exceptions: liver function was tested by the bromsulfalein excretion method; and kidney function was tested by phenolsulfonphthalein excretion.…”

Section: Methodsmentioning

confidence: 99%

Physiologic Action of Clostridium Oedematiens (Novyi) Toxin in Dogs 123

Aub¹,

Zamecnik²,

Nathanson³

1947

J. Clin. Invest.

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“…On the basis of the information presently available we may en vision a qualified picture of the mechanism of gas gangrene infec (180), and collagenase may add its characteris tic activity to create the pulped muscle appearance generally seen in gangrene. This evidence is most complete for C. perfringens, but probably applies as well to those other clostridia which are able to initiate gas gangrene infections.…”

Section: Acquired Immunity Against Infectious Disease 253mentioning

confidence: 99%

“…Zamecnik, Nathanson & Aub have described these for C. perfringens(180) and for C. novyi(181), and Pasternack & Bengston (182) for C. septicum. C. perfringens toxic filtrate pro duces gross intravascular hemolysis and fall in blood pressure ;C. novyi toxin acts principally upon the peripheral vascular system; and with C. septicum filtrate cardiotoxic and nephrotoxic proper ties predominate.Some information regarding successful immunization against gas gangrene by the use of toxoids has been available for years,but a great deal was added during the latter years of World War Annu.…”

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confidence: 99%