H2-receptor antagonism is not pro-arrhythmic in a chronic canine model.
Seven to 28 days after coronary artery ligation, programmed electrical stimulation was performed in conscious dogs. Groups of 6 previously inducible dogs in which no arrhythmia could presently be achieved were randomly allocated to receive quinidine, cimetidine, ranitidine or placebo. Results were assessed for the drugs' ability to induce ventricular tachycardia or fibrillation, and compared with placebo using Fisher's Exact Test. In the placebo group 4/6 dogs remained unchanged, one developed an arrhythmia, and one died. With quinidine, 3/6 dogs developed an arrhythmia (0.5 mg/kg, 4.0 mg/kg, 4.0 mg/kg) and three died (4 mg/kg, 8 mg/kg, 16 mg/kg) (p less than 0.05 compared with placebo). With cimetidine, 4/6 dogs remained unchanged, one developed an arrhythmia after 4 mg/kg, and one died after 0.5 mg/kg. After ranitidine 3/6 dogs remained unchanged and three died (1.0 mg/kg, 4.0 mg/kg, 16.0 mg/kg). PR, QTc, QRS, refractory periods, and mean systolic pressure remained unchanged after placebo, cimetidine, and ranitidine, but QTc increased (p less than 0.05) and mean systolic pressure fell (p less than 0.01) after quinidine. Heart rate did not change following placebo, but increased (p less than 0.05) after each of the three drug treatments. These results fail to show a significant arrhythmogenic effect of cimetidine or ranitidine in a model validated by the significant pro-arrhythmic effects of quinidine. The cause of death in all cases was ventricular fibrillation.
Uprichard
A C
AC
Department of Therapeutics and Pharmacology, Queen's University of Belfast, Northern Ireland.
Harron
D W
DW
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000209:etiology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D002927:Cimetidine / Q000494:pharmacology*; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006635:Histamine H2 Antagonists; D008297:Male; D011899:Ranitidine / Q000494:pharmacology*; D013997:Time Factors
D006635:Histamine H2 Antagonists; D002927:Cimetidine; D011899:Ranitidine