Showing papers by "Stanley Nattel published in 1985"

Effect of sympathetic tone on ventricular arrhythmias during circumflex coronary occlusion.

Abstract: To determine if the sympathetic nervous system exerts an arrhythmogenic effect on the ischemic myocardium independent of heart rate, the proximal circumflex coronary artery was occluded for 1 h in 62 open-chest, anesthetized dogs. The atrial rate was maintained at 200/min, and the vagosympathetic trunks were transected in all dogs. The total incidence of ventricular fibrillation was 35% in 20 dogs with intact stellates and not significantly different from the incidence of ventricular fibrillation (15%) in another 20 dogs in which both stellate ganglia had been decentralized. Electrical stimulation of the left ansae subclavia (3 Hz, 2 ms, 6-8 V) in the remaining 22 dogs significantly increased the incidence of ventricular fibrillation to 73% (P less than 0.05). The magnitude of S-T segment elevation in the lead II electrocardiogram 90 s after occlusion was 0.69 +/- 0.08 mV in the group with left ansae stimulation and significantly elevated (P less than 0.01) compared with dogs with intact stellates (0.35 +/- 0.06 mV) and with the denervated dogs (0.19 +/- 0.05 mV). The data indicate that the sympathetic nervous system is capable of a direct arrhythmogenic influence on the ischemic myocardium independent of heart rate. The rate-independent arrhythmogenic effects of the sympathetic nervous system may be mediated by an increase in severity of the ischemic insult.

Frequency-dependent effects of amitriptyline on ventricular conduction and cardiac rhythm in dogs.

Abstract: Although overdoses of tricyclic antidepressant are known to produce both sinus tachycardia and ventricular tachyarrhythmias in man, these have been assumed to occur by independent mechanisms. This study was designed to evaluate the relationship of ventricular activation frequency to the cardiotoxic effects of amitriptyline. When amitriptyline was infused into dogs with formalin-induced atrioventricular (AV) block to evaluate a broad range of pacing frequencies, the drug produced dose-related QRS prolongation that was markedly frequency dependent. Similar frequency-dependent depression of the maximum rate of depolarization (Vmax) was noted for canine Purkinje fibers superfused with amitriptyline in vitro. The time constant of recovery from amitriptyline-induced block was dose independent and averaged 228 msec in vivo and 216 msec in vitro. When amitriptyline was infused into dogs with intact AV conduction, sinus tachycardia occurred within 15 min, followed by progressive QRS prolongation and ventricular tachyarrhythmias after an average 29 min. Slowing of sinus rate by vagal stimulation (seven dogs) or intravenous metoprolol (five dogs) reproducibly reversed the QRS prolongation and ventricular tachyarrhythmias caused by amitriptyline. These studies show that amitriptyline produces frequency-related depression of ventricular conduction in vivo, with a time dependence similar to effects on the maximum rate of depolarization in vitro. Interventions that slow heart rate reverse the adverse effects of amitriptyline on ventricular conduction and cardiac rhythm.

Age-dependent lidocaine disposition in patients with acute myocardial infarction.

Abstract: To evaluate age-dependent changes in lidocaine disposition in patients with acute myocardial infarction, we measured plasma concentrations of lidocaine and its metabolites monoethylglycinexylidide and glycinexylidide after discontinuation of a maintenance lidocaine infusion. Plasma lidocaine clearance was calculated by dividing the lidocaine concentration at the end of the infusion into the maintenance infusion rate. Lidocaine clearance in 35 patients was related to body weight and was reduced by heart failure. Heart failure was more common in the elderly, occurring in 15 of 27 (56%) patients over 65 years old and seven of 29 (24%) patients under 65 years old. There was a reduction in lidocaine clearance with age due, in part, to lower body weight and a higher prevalence of heart failure in the elderly. Multilinear regression analysis showed that age and weight contributed to the prediction of lidocaine plasma clearance in patients with and without heart failure. Age was a particularly important predictor of lidocaine clearance in patients with heart failure. Adjustment of lidocaine maintenance doses based on age, weight, and heart failure may help control the frequency of lidocaine adverse reactions in the elderly. Clinical Pharmacology and Therapeutics (1985) 37, 381–386; doi:10.1038/clpt.1985.58