Pharmacodynamics and pharmacokinetics of oral pirmenol.

The efficacy, pharmacokinetics, and pharmacodynamics of pirmenol, a class Ia antiarrhythmic agent, were studied in patients with frequent symptomatic premature ventricular complexes (PVCs). Pirmenol was given every 12 hours to eight patients in a dose-ranging protocol, and median PVC suppression of 94% (range 72% to 100%) was achieved. The median effective pirmenol dose was 300 mg/day (range 200 to 500 mg/day), and mean (+/- SD) trough plasma pirmenol concentration at the effective dose was 0.98 +/- 0.29 micrograms/ml. The mean half-life of elimination was 10.5 +/- 2 hours. There was considerable overlap among patients with respect to plasma pirmenol concentration and times at which PVC frequency returned to 25%, 50%, and 75% of baseline during drug washout trials. Altering pirmenol's dose interval (while maintaining a constant daily dose) from 12 to 6 hours did not improve drug efficacy. Pirmenol was given to seven patients for long-term therapy (24 to 44 months). Median PVC suppression at 24 months was 70%. Pirmenol is safe and well tolerated, and it can be administered twice daily for PVC suppression.

Digital subtraction angiography in angioplasty of total coronary artery occlusion.

This report describes a digital subtraction angiographic technique used to simultaneously display the proximal and distal segments of three totally occluded coronary arteries in two patients undergoing percutaneous transluminal coronary angioplasty (PTCA). The advantage of this technique over routine cineangiography for PTCA of total occlusions is illustrated.

Cryosurgical versus catheter ablation of the atrioventricular junction.

Results of catheter ablation of the atrioventricular (AV) junction in 41 patients were compared with results of cryosurgical ablation in 42 patients. Mean follow-up was 29 months among patients who underwent catheter ablation and 53 months among those who underwent cryosurgical ablation. In both groups complete heart block was produced in most patients (88% in the catheter ablation group, 86% in the cryosurgery group), and similar proportions of patients continued to receive antiarrhythmic drugs (27% in the catheter ablation group, 36% in the cryosurgery group). However, the short-term morbidity rate was significantly lower among patients who underwent catheter ablation (12% vs 42%) (p = 0.004). Long-term mortality and morbidity rates were not significantly different; most deaths were related to underlying cardiopulmonary disease and morbidity to problems with permanent pacemakers. Both catheter ablation and cryosurgical ablation of the AV junction are effective in creating complete AV block and controlling supraventricular tachycardia in medically refractory patients. Because catheter ablation is associated with lower short-term morbidity and avoids the need for a major surgical procedure, it is preferable to cryosurgical ablation of the AV junction when permanent abolition of AV conduction is necessary.

Pharmacokinetics and pharmacodynamics of esmolol administered as an intravenous bolus.

Esmolol is a new ultra-short-acting beta-adrenergic receptor blocking agent that may be useful in the treatment of patients with heart disease. We gave esmolol as an intravenous bolus injection (over 30 seconds) to 12 healthy men in a dose-ranging study; each subject received two doses. Our dosing schedule began with 30 mg in the first subject and ended with 100 mg and 150 mg in the final four subjects. We measured blood esmolol concentration, PR interval, QRS duration, QTc interval, cardiac cycle, systolic blood pressure, and diastolic blood pressure. Esmolol doses of 150 mg produced blood esmolol concentrations of 0.868 to 1.47 micrograms/ml. The peak PR interval recorded after esmolol was significantly longer than the control PR interval in four subjects who received 100 and 150 mg doses (192 +/- 7.9 msec vs. 177 +/- 10.6 msec; P = 0.00002). Peak prolongation of the PR interval was recorded 6 to 10 minutes after the bolus, at which time blood esmolol concentrations were negligible. Esmolol did not consistently affect any other pharmacodynamic variable. Giving esmolol as an intravenous bolus injection may be a simple alternative to loading and maintenance infusion in some clinical settings.

Incidence of symptomatic tachycardia in untreated patients with paroxysmal supraventricular tachycardia.

The purpose of this article is to investigate the occurrence of symptomatic paroxysmal supraventricular tachycardia (PSVT) in untreated patients and to assess factors that influenced its occurrence. We studied 34 patients with this arrhythmia during an observation period in which they received no antiarrhythmic drug therapy for up to 90 days. Recurrence of PSVT was documented by telephone transmission of the electrocardiogram. Each patient was allowed to have exactly one episode of tachycardia before being removed from the study. We measured how long patients remained free of their tachycardia (the tachycardia-free period) and heart rate during tachycardia. Twenty-nine of the 34 patients had an attack of symptomatic tachycardia within the 90-day observation period. The proportion of patients who had not had any symptomatic PSVT by each day of follow-up was calculated using the Kaplan-Meier method as follows: 75% by day 3, 50% by day 19, 25% by day 36, and 17% by day 90. Patients with any other heart or lung disease had significantly shorter tachycardia-free periods. The mean heart rate during spontaneous tachycardia was 203.5 +/- 34.9 beats per minute (range, 142 to 288 beats per minute). Patients with longer tachycardia-free periods had significantly faster heart rates during tachycardia.