Reduction of ventricular fibrillation threshold by histamine: resolution into separate H1 and H2-mediated components

The effects of histamine and the selective agonists impromidine (H2-agonist) and 2-(2-thiazolyl ethylamineXH1-agonist) on yen-tricular fibrillation threshold were tested in the isolated guinea-pig heart. All three compounds produced reversible concentra-tion-dependent decreases in ventricular fibrillation threshold. Ventricular fibrillation threshold reduction was not secondary to the positive chronotropic effect of the three compounds. Computer analysis of the data using appropriate theoretical models suggests that the net effect of histamine on ventricular fibrillation threshold is the resultant of two components: H1 and H2. Pyrilamine inhibited the H1-mediated effects of histamine on ventricular fibrillation threshold with a Kb value of 0.449 nM. H1- and H2-receptors mediating ventricular fibrillation threshold reduction differ in their relative sensitivity to histamine (H1&gt