Analysis of the Biphasic Response in Cardiac Anaphylaxis to an Active Streptococcal Toxin

Abstract

Guinea pig atria, sensitized in vitro with rabbit anti-streptolysin O, release histamine when challenged with inactive toxin and both histamine and acetylcholine when tested with the active (reduced) form. Challenge with active toxin results in a transient cholinergic depressor reaction which precedes the long-lasting augmentor effect of histamine. This biphasic response was analyzed by (1) varying the intensity of the anaphylactic phase alone, (2) by activating the toxin in the reaction system after initiating anaphylaxis by inactive toxin, and (3) by simulation of the biphasic response, using the mediators themselves. When the atrium is presented both substances simultaneously, the response to acetylcholine precedes that to histamine. The powerful atrial cholinesterase activity explains the transience of the toxic phase. The transient and oppositely directed effects of acetylcholine on the cardiac action potential always override those of histamine.