1. The rapid death which occurred after intravenous injection of activated streptolysin O from. Group A or Group C streptococci was always preceded by profound electrocardiographic alterations. After several multiples of the LD50 doses, cardiac electrical arrest or fibrillation could occur within 2 to 4 seconds after completion of the injection.

2. The streptolysin O preparations used were rather highly purified, but were known to be contaminated with small amounts of one or two other immunologically distinct components. Evidence that the observed results were due to streptolysin O was obtained by tests of the reversibly oxidized materials, and by cholesterol inactivation, as well as by in vivo protection with human gamma globulin rich in antistreptolysin antibodies.

3. Four non-streptolysin streptococcal antigens, partially or highly purified, failed to produce similar electrocardiographic changes, and were much less toxic. One of these was 3 X recrystallized and 1 X rechromatographed streptococcal proteinase. Shigella paradysenteriae type III endotoxin also did not produce striking electrocardiographic abnormalities.

4. A working hypothesis has been developed implicating streptolysin O as the etiological streptococcal factor responsible for the pathogenesis of rheumatic fever, which seems to account for the principal features of this illness.

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