Interaction between myocardial depressant factor and vasoactive mediators with ischemia and shock.

A variety of endogenously formed vasoconstrictor substances circulate in the blood and act as mediators in ischemia and shock states. These humoral substances are chemically diverse and include peptides, lipids, and aromatic amines. One of the novel peptides, myocardial depressant factor (MDF) and several interesting lipids, including thromboxane A2 (TxA2), leukotriene D4 (LTD4), and platelet-activating factor (PAF) are very potent substances having a broad profile of pathophysiological actions. Some of the effects of MDF include myocardial depression, constriction of splanchnic vessels, and impairment of phagocytosis. TxA2 primarily constricts blood vessels, aggregates platelets, and increases membrane permeability. LTD4 is a potent vasoconstrictor and bronchoconstrictor and promotes leakage of fluid out of blood vessels. PAF activates platelets, depresses cardiac function, constricts airways, and enhances fluid leakage from the intravascular compartment. Thus vasoconstriction is common to all these mediators. Moreover, these vasoactive substances have common mechanisms of release and interact to exacerbate ischemia and contribute to the pathogenesis of a variety of shock states. New pharmacological approaches to blocking the formation and action of these mediators have provided interesting insights into the pathophysiology of shock.