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Hemodynamic effects of a new antiarrhythmic agent: cibenzoline
Insights
Cibenzoline, a new anti-arrhythmic drug, significantly reduced cardiac output and left ventricular function in patients. Caution is advised for patients with compromised heart function due to its negative inotropic effects.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Cibenzoline is a novel anti-arrhythmic agent with multi-class Vaughan-Williams properties.
- Its hemodynamic effects require thorough investigation, especially in patients with pre-existing cardiac conditions.
Purpose of the Study:
- To evaluate the hemodynamic impact of intravenous Cibenzoline in patients undergoing cardiac catheterization.
- To assess the relationship between Cibenzoline plasma levels and observed hemodynamic changes.
Main Methods:
- Hemodynamic parameters including left ventricular pressure and right-sided pressures were measured in 9 patients.
- Measurements were taken at baseline and at intervals after intravenous Cibenzoline administration (1 mg/kg).
- Left ventricular peak positive dP/dt and Vmax were calculated, and plasma Cibenzoline levels were quantified.
Main Results:
- Cardiac index decreased by 20% at 5 minutes, with recovery after one hour. Stroke index fell, while heart rate remained stable.
- Ventricular filling pressures increased, and peripheral and pulmonary resistances rose significantly.
- Left ventricular peak positive dP/dt and Vmax showed significant reductions, correlating with plasma Cibenzoline levels.
Conclusions:
- Intravenous Cibenzoline exerts significant negative inotropic effects, impacting cardiac output and contractility.
- Therapeutic plasma levels of Cibenzoline are associated with a notable decrease in cardiac output and left ventricular function.
- Caution is recommended when using Cibenzoline in patients with severely depressed ventricular function.
Abstract:
The hemodynamic effects of an intravenous dose of 1 mg/kg of Cibenzoline, a new anti-arrhythmic agent with properties of classes I, III and IV of the Vaughan-Williams classification, were studied in 9 patients during routine cardiac catheterization. Six patients had valvular heart disease (aortic insufficiency in 5 and mitral stenosis in 1), one patient had ischemic heart disease, one patient had alcoholic cardiomyopathy and the remaining patient had coarctation of the thoracic aorta. Left ventricular pressure and right sided intracardiac pressures were recorded using a high fidelity transduced and a Swan-Ganz catheter respectively. The first derivative of the left ventricular pressure was obtained electronically and Vmax calculated by linear extrapolation to zero load of the contractile element shortening velocity--left ventricular pressure relationship. Plasma levels of Cibenzoline were measured by gas liquid chromatography. All these parameters were obtained under baseline conditions and then 5, 10, 20, 40 and 60 minutes after intravenous administration of Cibenzoline. Cardiac index fell by 20% 5 minutes after the injection of Cibenzoline, and returned to control after one hour only. This fall was primarily related to a decrease in stroke index, since heart rate remained virtually unchanged. Right and left ventricular filling pressures increased significantly from the 5th to the 40th minute. Aortic systolic pressure fell by approximately 6%, without any change in mean and diastolic aortic pressures. Peripheral and pulmonary resistances increased at 20 minutes by 33% and 45%, respectively. Left ventricular peak positive dP/dt and Vmax decreased significantly at 5 minutes and remained below the baseline value until 60 minutes by 9% and 11% respectively. Percent changes in cardiac index, dP/dt and Vmax were significantly correlated to cibenzoline plasma levels (r = 0.85, 0.79, 0.74 respectively; n = 45). Thus, doses achieving plasma levels within the reported therapeutic range (250-350 ng/ml) would be expected to result in a 8-12% decrease in cardiac output associated with 12-17% and 15-21% reduction of left ventricular dP/dt and Vmax respectively. These data indicate that cibenzoline exerts significant negative inotropic effects. Its use in the subset of patients with severely depressed ventricular function warrants caution.