Procainamide delivery to ischemic canine myocardium following rapid intravenous administration.

SUMMARY This study delineates the time course of procainamide accumulation in myocardium afterbolus administratio andn it relationshis top regiona l myocardial bloo The lefd flowt circumfle. xcoronary artery was ligated in 28 open-chest dogs. This was followed 40 minutes later by injection intothe left atrium of labeled microspheres 14. C-labeled procainamide, 1.5 mg/kg, was then administered a sa singl 1-minute infusioe n in 24 dogs, and four dogs were kille adt each of six different times (1.5-15minutes) after onse of drut g infusion In fou. r additional th dogse sam,e dos oef labeled dru wag sadministered as a 1-minut infusioe n repeated ever 5 minutesy ; afte thr e fifth dose th,e animals werekilled. Myocardial sections were analyze for regionad l blood flo anw d regional procainamide concen-tration. In the ischemic region, procainamide accumulated more slowly, and peak concentrations werelower than in the nonischemic region, being lowes int the most severely ischemic sections The dru. gwas thus distributed heterogenously throug the myocardiuh m early after bolus administration. Overtime, however, this distribution became more homogenous with concentrations in nonischemic sectionsfalling off more rapidly tha inn ischemic sections. Predicted steady state concentrations were achievedafter 15 minutes in mildly ischemic sections (0.31-0.90 ml/mi per gn) but had not been reached by 25minutes in severely ischemic sections We conclud. e that ischemic myocardium a potentia, l sit ofeantiarrhythmic drug action, represent as progression of pharmacokinetic compartments increasinglydistal from the central compartment, depending o thn e severity of ischemia. CircRes 46: 789-795, 1980