cinnarizine and Coronary-Disease

In male rats, anaesthetized with pentobarbitone, ligation of the main left coronary artery causes an early phase of ventricular arrhythmias which last about 30 min. In approximately 60% of control animals, ventricular fibrillation occurs but since spontaneous reversion to sinus rhythm may occur, mortality is of the order of 30%. When administered intravenously 15 min prior to ligation, verapamil (0.01 and 0.05 mg kg-1), prenylamine (0.5 mg kg-1), flunarizine (0.1, 0.25, 0.5 and 1.0 mg kg-1) and cinnarizine (0.25, 0.5 and 1.0 mg kg-1) protected against these arrhythmias. Higher doses of verapamil (0.1 and 0.5 mg kg-1), prenylamine (5 mg kg-1) and flunarizine (2.5 mg kg-1) did not afford a similar protection and mortality was increased to or above control values. Death was due in prenylamine-treated rats to atrioventricular block leading to asystole whereas in those administered verapamil or flunarizine it was a consequence of persistent ventricular fibrillation. Prior to ligation, a sustained fall in mean arterial blood pressure was observed only following the administration of the highest doses of prenylamine, flunarizine and cinnarizine. Heart rate was reduced by administration of only the highest dose of prenylamine. These studies show that although the four calcium antagonists studied, i.e. verapamil, prenylamine, flunarizine and cinnarizine do suppress ischaemia-induced arrhythmias, this protective effect may be limited to a narrow concentration range.

Topics: Anesthesia; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Blood Pressure; Calcium Channel Blockers; Cinnarizine; Coronary Disease; Flunarizine; Heart Rate; Male; Prenylamine; Rats; Rats, Inbred Strains; Verapamil

We tested the effects of the calcium antagonists lanthanum, diltiazem, and flunarizine on the development of atherosclerosis in rabbits fed a 2% cholesterol diet. The drugs were given orally and were well tolerated. In the cholesterol control animals, 52.2% of the thoracic aortic intimal surface was Sudan IV positive. This was reduced by 37% (p less than 0.05) with lanthanum, 37% (p less than 0.05) with diltiazem, and 34% (p less than or equal to 0.06) with flunarizine. In all cholesterol-fed animals, the intramural, but not subepicardial, coronary arteries were severely diseased. The extent and distribution of this disease were not altered by the various drug interventions. Thus, the calcium antagonists lanthanum, diltiazem, and flunarizine suppress atherogenesis of the rabbit aorta but have no effect on the extent or distribution of atherosclerosis in the intramural coronary arteries.

Topics: Animals; Aortic Diseases; Arteriosclerosis; Calcium Channel Blockers; Cholesterol, Dietary; Cinnarizine; Coronary Disease; Diltiazem; Female; Flunarizine; Lanthanum; Organ Size; Rabbits