The effect of pretreatment with moricizine on early arrhythmia resulting from myocardial ischemia in rats.
Moricizine (moracizine) is a new class I antiarrythmic drug which is undergoing a large scale clinical trial at present. A rat model was used to compare the effects of moricizine (5 mg/kg i.v.), disopyramide (DSP 5 mg/kg i.v.) and mexiletine (MXT 5 mg/kg i.v.) on early ventricular arrhythmias occurring within 30 min after ligation of the left coronary artery. After intravenous administration, all three drugs slowed the heart rate significantly (p less than 0.01), and compared to the control group only moricizine significantly increased the systolic, diastolic and mean arterial blood pressures. The total number of premature ventricular complexes were as follows; control group (n = 9); 1666 +/- 250 beats, moricizine group (n = 7); 1645 +/- 417 beats (NS), DSP group (n = 10); 325 +/- 155 beats (p less than 0.01 vs control) and MXT group (n = 10); 733 +/- 147 beats (p less than 0.01 vs control). The incidence of primary ventricular fibrillation, was significantly reduced by DSP and MXT (10% reduction and 20% reduction respectively) (p less than 0.05), while moricizine (incidence 80%) had no effect in comparison to the control group (incidence 90%). Death due to arrhythmia was completely abolished by DSP and MXT; although moricizine showed a slight tendency to increase the mortality rate, but the difference was not significant. In conclusion, moricizine has no obvious protective effect on early ventricular arrhythmias resulting from coronary artery occlusion in rats.
He
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Second Department of Internal Medicine, Yamanashi Medical College, Japan.
Komori
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Tamura
K
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Hashimoto
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K
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology; D003327:Coronary Disease / Q000150:complications* / Q000503:physiopathology; D004206:Disopyramide / Q000494:pharmacology / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008801:Mexiletine / Q000494:pharmacology / Q000627:therapeutic use; D016293:Moricizine / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains
D008801:Mexiletine; D016293:Moricizine; D004206:Disopyramide