Effects of histamine on ouabain-induced ventricular fibrillation in guinea pigs

The effects of histamine on ouabain (1 microM)-induced ventricular fibrillation (VF) were studied in Langendorff hearts of guinea pigs. Histamine 0.5-10 microM induced a concentration-dependent shortening of incubation period of VF induced by ouabain. In the presence of cimetidine (CMT) 3 microM, the concentration-response curve (CRC) of histamine shifted to the right in a parallel fashion, whereas diphenhydramine (DPH) 4 microM failed to antagonize the effects of histamine. CMT shifted the CRC to right in the same extent no matter DPH was present or not. The synergic effects of histamine on the ouabain-induced VF were not secondary to its positive chronotropic effect. In anesthetized guinea pigs, iv histamine 1.2 mg/kg/h decreased the doase of iv ouabain (2.8 microg/min) required to induce VF. The effect of histamine was antagonized by iv CMT 15 mg/kg/h but not by iv DPH 5 mg/kg/h. These results suggest that only H2-receptors are involved in mediating the synergic effects of histamine on ouabain-induced VF in vitro and in vivo.