Anaphylactic shock (AS) was induced in 15 monkeys, and their hemodynamics were studied in order to identify the mechanisms initiating the low cardiac output (CO) state. Further, in 16 monkeys various substances were used with the aim of mimicking or antagonizing the changes in AS. Initial peripheral collapse was indicated by lowering of the right atrial pressure (RAP). The subsequent development of pulmonary hypertension increased RAP and, by extending venous pooling, reduced filling of the left heart. The degree of pulmonary hypertension or arterial hypotension was a poor indicator of the fall in CO. Hypoxemia and dysrythmias occurred occasionally, but early hemoconcentration was not found. Light depression of CO (—42%), due to venous pooling and reduction in left heart filling, could be corrected by fluid administration. In contrast, severe depression of CO (—81%) associated with ST-T depression and with decreased cardiac contractility responded less to the fluid load, suggesting that myocardial failure was partly responsible for the low output state.

Inhibition of prostaglandin (PG) synthesis by indomethacin did not prevent the development of AS. Injections of PGE2 and PGF, alone or together with histamine (Hi), did not mimic AS. PGE2 induced hypotension accompanied by an increase in CO, and PGF induced general vasoconstriction and a somewhat diminished CO. Hi induced hypotension and pulmonary hypertension; CO increased after low doses but decreased after sublethal doses. Compound 48/80, a liberator of Hi and slow-reacting substance (SRS), imitated Hi effects initially, but later mimicked a minor state of AS. Infusion of FPL 55712, a selective antagonist of SRS, prevented AS, and general vasoconstriction occurred instead. In this model of AS, SRS is a more important mediator than Hi or PG.