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Effects of the Na+ antagonist cibenzoline on left ventricular function of postischemic hearts
H M Hoffmeister1, M E Beyer, L Seipel
1Abt. III, Eberhard-Karls-Universität, Tübingen, Germany.
Insights
The antiarrhythmic drug cibenzoline significantly reduced heart function in rats with postischemic left ventricles. This sodium antagonist caused notable cardiodeperessant effects, especially in compromised cardiac muscle.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Negative inotropic effects of antiarrhythmic drugs pose risks, particularly in patients with impaired left ventricular function.
- Cibenzoline, a Class I antiarrhythmic drug, acts as a sodium (Na+) antagonist.
Purpose of the Study:
- To investigate the circulatory and myocardial effects of cibenzoline in rats with normal and postischemic myocardium.
- To assess the impact of cibenzoline on cardiac function in compromised left ventricular conditions.
Main Methods:
- Utilized 47 open-chest rats, divided into normal and postischemic myocardium groups.
- Administered cibenzoline (2 mg/kg i.v.) and compared hemodynamic measurements (cardiac output, dP/dtmax, heart rate, aortic pressure) to saline controls.
- Performed isovolumic registrations to evaluate left ventricular systolic pressure and peak dP/dtmax.
Main Results:
- In postischemic rats, cibenzoline significantly decreased cardiac output (38%), dP/dtmax (30%), and peak isovolumic dP/dtmax (19%).
- Heart rate, mean aortic pressure, and systemic resistance were also significantly reduced (22%, 22%, and 20% respectively).
- Normal rats showed no significant hemodynamic changes after cibenzoline administration.
Conclusions:
- Standard doses of the sodium antagonist cibenzoline can induce significant cardiodeperessant effects.
- These effects are particularly pronounced in postischemic left ventricles with reduced contractile function.
- Cibenzoline's potential for cardiac depression warrants careful consideration in patients with left ventricular dysfunction.
Abstract:
The negative inotropic effect of antiarrhythmic drugs is a major drawback in antiarrhythmic drug therapy, especially in patients with reduced contractile function of the left ventricle. The circulatory and myocardial effects of the new class I antiarrhythmic drug (a Na+ antagonist), cibenzoline (2 mg/kg i.v.), were investigated in 47 open-chest rats with normal and postischemic myocardium (3 x 4 minutes of global ischemia). Hemodynamic measurements in the intact circulation and isovolumic registrations (peak isovolumic left ventricular systolic pressure and peak isovolumic dP/dtmax) were compared to saline controls. In rats with postischemic myocardium, cibenzoline caused a significant (p < 0.001) decrease in the cardiac output for 38%, in the dP/dtmax for 30%, and in the peak isovolumic dP/dtmax for 19% at the end of infusion (compared to the control). The heart rate was reduced by 22% (p < 0.001), the mean aortic pressure by 22% (p < 0.001), and the calculated systemic resistance by 20% (p < 0.001). In contrast to the results with postischemic myocardium, no important changes in the hemodynamics were detectable after an identical dose in normal animals without left ventricular dysfunction. The results indicate that standard doses of the Na+ antagonist cibenzoline may induce significant cardiodeperessant effects on postischemic left ventricles with reduced function.