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. 1968 Nov 30;128(6):1401–1424. doi: 10.1084/jem.128.6.1401

AN ANALYSIS OF THE TOXIC ACTIONS OF PURIFIED STREPTOLYSIN O ON THE ISOLATED HEART AND SEPARATE CARDIAC TISSUES OF THE GUINEA PIG

Bruce A Reitz 1, Denis J Prager 1, George A Feigen 1
PMCID: PMC2138580  PMID: 4176938

Abstract

The response of isolated guinea pig hearts to perfusion with purified streptolysin O is characterized by a rapid, but transient, decrease in rate and amplitude of contraction; these reactions are superimposed upon a gradual, irreversible, loss of ventricular contractility. At ventricular standstill, the atria continue to beat spontaneously in a normal way. Isolated ventricle strips prepared from such preparations can be driven electrically, and their behavior is functionally indistinguishable from that of similar preparations made from normal hearts. Tests on spontaneously beating isolated atrial pairs show that the toxin induces a dose-dependent, reversible, decline in rate and amplitude which is accompanied by a marked, but transient, increase in the velocity of repolarization of the intracellular potential. The atrial reactions were completely blocked by atropine and potentiated by eserine. Acetylcholine was detected in the perfusates obtained by incubating a large pool of atrial tissue with active toxin, supporting the inference that the transient mechanical and electrophysiological reactions to toxin might be consequences of the release of acetylcholine from these tissues by the active toxin. Control studies showed that only the active toxin had the capacity to induce the cardiac responses. The toxin was active only in the reduced but not the oxidized form. The effects of the active toxin were modified if it were heated prior to challenge, and they could be neutralized by specific antiserum and inhibited by cholesterol. Since the driven ventricle strip was mechanically and electrophysiologically insensitive to streptolysin O, the irreversible changes in the whole heart must have occurred because of a defect in the atrioventricular conduction system.

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Selected References

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  1. BERNHEIMER A. W., CARLSON A. S., FREEMAN E. B., KELLNER A. Loss of myocardial contractility induced in isolated mammalian hearts by streptolysin O. J Exp Med. 1956 Sep 1;104(3):361–373. doi: 10.1084/jem.104.3.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bernheimer A. W., Cantoni G. L. THE CARDIOTOXIC ACTION OF PREPARATIONS CONTAINING THE OXYGEN-LABILE HEMOLYSIN OF STREPTOCOCCUS PYOGENES : I. INCREASED SENSITIVITY OF THE ISOLATED FROG'S HEART TO REPEATED APPLICATION OF THE TOXIN. J Exp Med. 1945 Mar 1;81(3):295–306. doi: 10.1084/jem.81.3.295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. FEIGEN G. A., MASUOKA D. T., THIENES C. H., SAUNDERS P. R., SUTHERLAND G. B. Mechanical response of the isolated electrically driven rat ventricle strip. I. Preparation and standardization. Stanford Med Bull. 1952 Feb;10(1):27–31. [PubMed] [Google Scholar]
  4. FEIGEN G. A., NIELSEN C. B., SUTHERLAND G. B. Differential action of ammonium chloride on the response of the sensitized gut to ovalbumin, serotonin, and histamine. J Immunol. 1957 Apr;78(4):240–245. [PubMed] [Google Scholar]
  5. FEIGEN G. A., VAUGHAN WILLIAMS E. M., PETERSON J. K., NIELSEN C. B. Histamine release and intracellular potentials during anaphylaxis in the isolated heart. Circ Res. 1960 Jul;8:713–723. doi: 10.1161/01.res.8.4.713. [DOI] [PubMed] [Google Scholar]
  6. GOULLET P., CORABOEUF E., BRETON D. ACTION D'UNE PR'EPARATION DE STREPTOLYSINE O PURIFI'EE SUR LE TISSU MYOCARDIQUE VENTRICULAIRE. C R Hebd Seances Acad Sci. 1963 Sep 2;257:1735–1738. [PubMed] [Google Scholar]
  7. HALBERT S. P., AUERBACH T. The use of precipitin analysis in agar for the study of human streptococcal infections. IV. Further observations on the purification of group A extracellular antigens. J Exp Med. 1961 Jan 1;113:131–158. doi: 10.1084/jem.113.1.131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. HALBERT S. P., BIRCHER R., DAHLE E. Studies on the mechanism of the lethal toxic action of streptolysin "O" and the protection by certain antiserotonin drugs. J Lab Clin Med. 1963 Mar;61:437–452. [PubMed] [Google Scholar]
  9. HALBERT S. P., BIRCHER R., DAHLE E. The analysis of streptococcal infections. V. Cardiotoxicity of streptolysin O for rabbits in vivo. J Exp Med. 1961 Apr 1;113:759–784. doi: 10.1084/jem.113.4.759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. HALBERT S. P., KEATINGE S. L. The analysis of streptococcal infections. VI. Immunoelectrophoretic observations on extracellular antigens detectable with human antibodies. J Exp Med. 1961 Jun 1;113:1013–1028. doi: 10.1084/jem.113.6.1013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. HALBERT S. P., SWICK L., SONN C. The use of precipitin analysis in agar for the study of human streptococcal infections. I. Oudin technic. J Exp Med. 1955 May 1;101(5):539–556. doi: 10.1084/jem.101.5.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. HALBERT S. P., SWICK L., SONN C. The use of precipitin analysis in agar for the study of human streptococcal infections. II. Ouchterlony and Oakley technics. J Exp Med. 1955 May 1;101(5):557–576. doi: 10.1084/jem.101.5.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. HALBERT S. P. The use of precipitin analysis in agar for the study of human streptococcal infections. III. The purification of some of the antigens detected by these methods. J Exp Med. 1958 Sep 1;108(3):385–410. doi: 10.1084/jem.108.3.385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. HOFFMAN B. F., SUCKLING E. E. Cardiac cellular potentials; effect of vagal stimulation and acetylcholine. Am J Physiol. 1953 May;173(2):312–320. doi: 10.1152/ajplegacy.1953.173.2.312. [DOI] [PubMed] [Google Scholar]
  15. Halpern B. N., Rahman S. Studies on the cardiotoxicity of streptolysin O. Br J Pharmacol Chemother. 1968 Mar;32(3):441–452. doi: 10.1111/j.1476-5381.1968.tb00445.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. MORTIMER E. A., Jr, RAMMELKAMP C. H., Jr Prophylaxis of rheumatic fever. Circulation. 1956 Dec;14(6):1144–1152. doi: 10.1161/01.cir.14.6.1144. [DOI] [PubMed] [Google Scholar]
  17. PETERSON N. S., FEIGEN G. A. Effect of [NO3] on atrial action potentials and contraction as modified by [Na] and [Ca]. Am J Physiol. 1962 May;202:950–956. doi: 10.1152/ajplegacy.1962.202.5.950. [DOI] [PubMed] [Google Scholar]
  18. Vurek G. G., Prager D. J., Feigen G. A. Antibody concentration and temperature as determinants of in vitro sensitization and histamine release in isolated cardiac tissues. J Immunol. 1967 Dec;99(6):1243–1253. [PubMed] [Google Scholar]

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