Procainamide delivery to ischemic canine myocardium following rapid intravenous administration

T. L. Wenger, D. J. Browning, C. E. Masterton, M. B. Abou-Donia, F. E. Harrell, R. J. Bache, H. C. Strauss

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

This study delineates the time course of procainamide accumulation in myocardium after bolus administration and its relationship to regional myocardial blood flow. The left circumflex coronary artery was ligated in 28 open-chest dogs. This was followed 40 minutes later by injection into the left atrium of labeled microspheres. 14C-labeled procainamide, 1.5 mg/kg, was then administered as a single 1-minute infusion in 24 dogs, and four dogs were killed at each of six different times (1.5-15 minutes) after onset of drug infusion. In four additional dogs, the same dose of labeled drug was administered as a 1-minute infusion repeated every 5 minutes; after the fifth 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 thus distributed heterogenously through the myocardium early after bolus administration. Over time, however, this distribution became more homogeneous with concentrations in nonischemic sections falling off more rapidly than in ischemic sections. Predicted steady state concentrations were achieved after 15 minutes in mildly ischemic sections (0.31-0.90 ml/min per g) but had not been reached by 25 minutes in severely ischemic sections. We conclude that 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.

Original languageEnglish (US)
Pages (from-to)789-795
Number of pages7
JournalUnknown Journal
Volume46
Issue number6
DOIs
StatePublished - Jan 1 1980

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