Acute effect of disopyramide on atrial fibrillation in the Wolff-Parkinson-White syndrome.
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Disopyramide was administered intravenously to 54 patients during atrial fibrillation and predominantly pre-excited QRS configuration at the time of electrophysiologic study. All patients had Wolff-Parkinson-White syndrome and no patient had coexistent heart disease. The drug was given during sustained atrial fibrillation (n = 45) or during sinus rhythm before induction of atrial fibrillation for patients whose atrial fibrillation was self-terminating in the control state (n = 9). Atrial fibrillation converted to sinus rhythm within 15 min after disopyramide in 37 (82%) of the 45 patients. The shortest RR intervals between two pre-excited cycles increased from 208 +/- 42 to 293 +/- 117 ms (p less than 0.0001). The average RR interval of all cycles prolonged from 332 +/- 60 to 396 +/- 117 ms(n = 45, p less than 0.0001). The 9 patients in whom pre-excitation was abolished after the drug had a significantly longer initial shortest RR interval than that of the 36 patients in whom pre-excitation persisted (246 +/- 47 versus 199 +/- 36 ms, p = 0.0022). No patients developed significant hemodynamic or other adverse effects after disopyramide. These data support the intravenous use of disopyramide in patients with normal ventricular function who have atrial fibrillation and a predominant ventricular response over an accessory atrioventricular pathway. (+info)
Simultaneous liquid-chromatographic determination of five antiarrhythmic drugs and their major active metabolites in serum.
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We report an isocratic "high-performance" liquid chromatographic method for the simultaneous measurement of tocainide, lidocaine, procainamide, quinidine, disopyramide, and their major active metabolites in serum. The drugs are extracted from 200 microL of serum at pH 9.5 with 1.5 mL of 1,2-dichloromethane, concentrated by evaporation, and separated on a CN-bonded-phase column at 40 degrees C (flow rate 2 mL/min) with a pH 7.1 mobile phase of acetonitrile/methanol/phosphate buffer (60/7/33, by vol); the phosphate buffer contains 10 mmol of KH2PO4 and 0.5 mmol of triethylamine per liter. The antiarrhythmic drugs elute in the K' (capacity factor) range of 1.43 (lidocaine) to 5.7 (disopyramide). Results vary linearly with drug concentration to at least 30 mg/L; the detection limit is 0.1-0.2 mg/L. Within-run precision (CV) ranges from 0.9% to 5.0% and day-to-day precision from 2.1% to 6.2%, depending on the specific drug and its concentration in serum. Extraction efficiencies vary from 76% to 85% and analytical recoveries from 98.5% to 103%. At toxic serum concentrations, several basic drugs may interfere with the assay of some antiarrhythmics, but only hydroxyzine, verapamil, and certain local anesthetics interfere at therapeutic concentrations. (+info)
Comparative haemodynamic effects of intravenous lignocaine, disopyramide and flecainide in uncomplicated acute myocardial infarction.
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A prospective study evaluated the comparative haemodynamic effects of three Class I antiarrhythmics (lignocaine Class 1B, disopyramide Class 1A and flecainide Class 1C) in 30 patients with uncomplicated acute myocardial infarction. Three groups, each of 10 patients, were allocated to lignocaine (Group I) 1.5 mg kg-1 i.v. loading dose over 10 min followed by infusion at 3 mg kg-1 h-1, disopyramide (Group II) or flecainide (Group III), both administered as a 1.0 mg kg-1 i.v. loading bolus over 10 min followed by a 1.6 mg kg-1 h-1 infusion for 120 min. The plasma levels of each drug were in the described therapeutic range. Lignocaine decreased cardiac index (-0.3 l min-1 m-2 (9%); P less than 0.05) and stroke volume index (-5 ml m-2 (11%); P less than 0.01). Systemic blood pressure, heart rate and systemic vascular resistance index were unchanged. There was a small increase (+3 mm Hg (30%); P less than 0.01) in pulmonary artery occluded pressure (PAOP). Both disopyramide and flecainide increased systemic blood pressure; the maximum increases for mean blood pressure were +10 mm Hg (11%) and +4 mm Hg (4%) respectively. Both drugs reduced cardiac index (-0.5 l min-1 m-2 (16%): -0.4 l min-1 m-2 (11%)) and stroke volume index (-11 ml m-2 (25%): -5 ml m-2 (11%)). There were increases in heart rate (+13: +5 beats min-1) pulmonary artery occluded pressure (+2: +3 mm Hg) and systemic vascular resistance index (+696: +275 dyn s cm-5 m2).(ABSTRACT TRUNCATED AT 250 WORDS) (+info)
Flecainide compared with a combination of digoxin and disopyramide for acute atrial arrhythmias after cardiopulmonary bypass.
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Fifty six adult patients were randomised to treatment with flecainide (group 1, n = 29) or a combination of digoxin and disopyramide (group 2, n = 27) for acute atrial fibrillation and flutter after cardiac surgery. Intravenous flecainide was given as a 2 mg/kg bolus over 20 minutes followed by an infusion (0.2 mg/kg per hour) for 12 hours. Group 2 were given digoxin (0.75 mg) intravenously followed two hours later by an intravenous bolus of disopyramide (2 mg/kg) and an infusion (0.4 mg/kg per hour) for 10 hours. Within 12 hours sinus rhythm was restored in 86% of the group 1 (25 patients) and 89% of the group 2 (24 patients). The median time to reversion was significantly shorter in group 1 (80 minutes, range 30-180 minutes) than group 2 (220 minutes, range 138-523 minutes). None of the patients in group 1 and four of the patients in group 2 had transient relapses into atrial fibrillation during the 12 hours of intravenous treatment. There were five late relapses in group 1 and seven in group 2 during subsequent oral treatment. Two group 1 patients and two group 2 patients showed adverse drug effects. Intractable ventricular arrhythmias occurred after five days of oral treatment in one patient (group 1) who had poor left ventricular function, hepatic impairment, and toxic concentrations of drugs at the time of death. Flecainide was as effective as the combination of digoxin and disopyramide and it acted significantly faster and was associated with fewer relapses. Monitoring of blood concentrations of flecainide is essential in patients with poor left ventricular function and hepatic impairment. (+info)
Haemodynamic effects of disopyramide in patients after open-heart surgery.
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Disopyramide phosphate was administered intravenously in a dose of 1.2 mg/kg body weight over one minute to nine patients after open-heart surgery and coronary artery bypass grafting. The haemodynamic changes were studied during and for 30 minutes after drug administration. Heart rate was unchanged throughout the study. During infusion the only significant changes were an increase in systemic blood pressure and systolic impedance signifying a direct increase in peripheral arterial resistance. Systemic blood pressure remained significantly higher for 10 minutes and systolic impedance for 30 minutes. Immediately after infusion max. dPower/dT, a measure of ventricular contractility, was significantly depressed for 15 minutes. Both cardiac output and aortic flow were significantly depressed for 30 minutes. DPTI/TTI, an estimate of subendocardial supply/demand ratio, showed an insignificant increase throughout the study. This study shows that intravenous disopyramide starts acting within 45 seconds of the start of infusion, directly increases peripheral arterial resistance, has a breif negative inotropic action, and does not reduce subendocardial blood flow. (+info)
Electrophysiological effects of melperone on isolated rabbit heart muscles.
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1. Electrophysiological effects of melperone on isolated atrial and ventricular muscle preparations of the rabbit were studied by a conventional microelectrode technique. 2. Melperone (3.3 microM) prolonged the action potential duration and effective refractory period of the atrial preparations without affecting the maximum rate of depolarization (Vmax). These effects of melperone on action potential duration and effective refractory period were inhibited by a low potassium perfusate (2.7 mM). 3. A high concentration of melperone (16.6 microM) decreased Vmax of atrial preparations. In ventricular muscles, melperone at either concentration decreased Vmax, although the increase in action potential duration was greater than in the atrium. 4. Depression of Vmax of ventricular muscles by melperone was found to be augmented by an increase of stimulation frequency and drug concentration. 5. The rate of onset of rate-dependent block of Vmax in ventricle was increased with drug concentration and frequency of stimulation. However, the time constant of recovery from rate-dependent block was almost constant. The kinetics of rate-dependent block of Vmax by melperone were approximately similar to those of quinidine and disopyramide. Consequently it is concluded that melperone possesses class 1a antiarrhythmic activity as well as class 3 activity. (+info)
Frequency- and voltage-dependent depression of maximum upstroke velocity of action potentials by pirmenol in guinea pig ventricular muscles.
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The frequency-dependency and voltage-dependency of the suppressing effect of pirmenol, a novel antiarrhythmic agent, on the maximum upstroke velocity (Vmax) of action potentials were examined and compared with those of disopyramide in guinea pig papillary muscles. Pirmenol in concentrations higher than 3 microM decreased Vmax with a slight increase in action potential duration. The reduction of Vmax by pirmenol was enhanced in a frequency-dependent manner over the range of 0.1-2.0 Hz. Pirmenol (30 microM) produced a small resting block (5.5%), whereas disopyramide (100 microM) produced a greater one (25.8%). The onset of frequency-dependent Vmax reduction at 2.0 Hz followed a monoexponential function with a slow rate constant (0.308 +/- 0.055 AP-1). The time constant for the recovery from the frequency-dependent block by pirmenol was also slow (33.5 +/- 5.4 sec), but faster than that of disopyramide (82.5 +/- 12.3 sec). At 1.0 Hz, pirmenol caused a shift (9.5 mV) of the curve relating the resting membrane potential and Vmax along the voltage axis in the hyperpolarizing direction. Thus, pirmenol is a Class Ia drug that has frequency- and voltage-dependent inhibitory actions on Vmax, and its onset and offset kinetics are relatively slow. (+info)
Actions of a newly synthesized compound (711389-S) on various types of experimentally induced arrhythmias in mammalian species in situ.
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We examined effects of 711389-S, a new antiarrhythmic agent, on ouabain-induced arrhythmias in dogs and guinea-pigs, aconitine-induced arrhythmias in dogs and mice, adrenaline-induced arrhythmias in dogs under an anesthetized condition, and arrhythmias induced by coronary artery ligation and occlusion by a glass bead in dogs under conscious and un-restrained conditions. 711389-S (1-3 mg/kg, i.v.) decreased the number of ventricular extrasystoles induced by ouabain in dogs, and the doses of ouabain required to induce various types of arrhythmias were increased by pretreatment of guinea-pigs with intraduodenal application of 711389-S (5-10 mg/kg). In mice, 711389-S (3 mg/kg, i.v. or 10 mg/kg, p.o.) significantly prolonged the time to onset of arrhythmias induced by aconitine infusion. Atrial fibrillation induced by a topical application of aconitine on the atrium was blocked by 711389-S (1 mg/kg, i.v.) in dogs. 711389-S (1-3 mg/kg, i.v.) depressed arrhythmias induced by adrenaline and restored the sinus rhythm by significantly decreasing the number of ventricular ectopic beats induced by coronary ligation or occlusion in dogs. Oral administration of 711389-S (10-30 mg/kg) in dogs markedly depressed the ventricular ectopic beats induced by coronary ligation. The half decay time of 711389-S after a single bolus injection of 711389-S ranged from 60 to 80 min. Results indicate that 711389-S has similar antiarrhythmic effects to those of other Class I antiarrhythmic agents in situ, and they suggest that this compound might have potential usefulness as a new type of antiarrhythmic agent for clinical use. (+info)