Hemodynamic effects of a new antiarrhythmic agent: XXXX .

@entity1 @entity64 @entity5354 @entity1498 @entity337 @entity7926 @entity741 @entity4794 @entity340
The hemodynamic effects of an intravenous dose of 1 mg/kg of @entity5354 , a new anti-arrhythmic agent with properties of classes I, III and IV of the Vaughan-Williams classification, were studied in 9 @entity1 during routine cardiac catheterization. Six @entity1 had @entity340 ( @entity337 in 5 and @entity4794 in 1), one @entity1 had @entity741 , one @entity1 had @entity7926 and the remaining @entity1 had @entity1498 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 @entity5354 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 @entity5354 . Cardiac index fell by 20% 5 minutes after the injection of @entity5354 , and returned to control after one hour only. This fall was primarily related to a decrease in @entity64 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 @entity5354 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 @entity5354 exerts significant negative inotropic effects. Its use in the subset of @entity1 with severely depressed ventricular function warrants caution.
