Procainamide delivery to ischemic canine myocardium following rapid intravenous administration.

Publisher Website
Google Scholar
Abstract
The time course of procainamide accumulation in myocardium after bolus administration and its relationship to regional myocardial blood flow were delineated. The left circumflex coronary artery was ligated in 28 open-chest dogs. This was followed 40 min later by injection into the left atrium of labeled microspheres. 14C-labeled procainamide, 1.5 mg/kg, was administered as a single 1 min infusion in 24 dogs, and 4 dogs were killed at each of 6 different times (1.5-15 min) after onset of drug infusion. In 4 additional dogs the same dose of labeled drug was administered as a 1 min infusion repeated every 5 min; after the 5th dose, the animals were killed. Myocardial sections were analyzed for regional blood flow and regional procainamide concentration. In the ischemic region, procainamide accumulated more slowly and peak concentrations were lower than in the nonischemic region, being lowest in the most severely ischemic sections. The drug was distributed heterogenously through the myocardium early after bolus administration. Over time this distribution became more homogenous with concentrations in nonischemic sections falling off more rapidly than in ischemic sections. Predicted steady-state concentrations were achieved after 15 min in mildly ischemic sections (0.31-0.90 ml/min per g) but had not been reached by 25 min in severely ischemic sections. Ischemic myocardium, a potential site of antiarrhythmic drug action, represents a progression of pharmacokinetic compartments increasingly distal from the central compartment, depending on the severity of ischemia.

This publication has 12 references indexed in Scilit: