Antigen-induced acceleration of automaticity in electrically depolarized ventricular myocardium of sensitized guinea...

Alterations in the membrane potentials during anaphylactic reactions were studied in ventricular muscle obtained from actively sensitized guinea pigs. The preparation was depolarized by constant current in a sucrose gap chamber to induce repetitive automatic action potential discharges (RAD) from the reduced membrane potentials (-60 to 0 mV). Application of specific antigen (human gamma-globulin, 6.8 X 10(-8) mol/L) markedly accelerated the firing frequency of the RAD. Overshoot and maximum rate of rise (Vmax) of the RAD increased during the initial 3 to 6 min of the antigenic challenge. The acceleration phase was followed by a long period of severe depression with marked reduction in the firing frequency of the RAD. These changes could be mimicked by an application of histamine (6.3 X 10(-7) mol/L) but were abolished in the presence of metiamide, a histamine H2-receptor antagonist (1 X 10(-5) mol/L). These findings indicate that an anaphylactic reaction transiently enhances the automaticity in electrotonically depolarized ventricular muscle, probably via the action of released histamine. Initial enhancement and later depression of the ectopic automaticity may be significant in the genesis of arrhythmias which occur during anaphylactic shock.