Pharmacokinetic analysis of coronary sinus retroinfusion in pigs. Ischemic myocardial concentrations in the left circumflex coronary arterial area using metoprolol as a tracer.

Myocardial availability of drug, using metoprolol as a tracer, in acutely ischemic myocardium in the area of the left circumflex (LCX) coronary artery was compared following standard intravenous (IV) administration and after coronary sinus retroinfusion. Seven open-chest farm pigs were subjected to a 21-minute occlusion of the LCX coronary artery. All animals received simultaneous IV tritium-labeled metoprolol (0.2 mg/kg) and unlabeled metoprolol (0.2 mg/kg) retrogradely into the coronary sinus. The drug administration was started after 1 minute of coronary artery occlusion and continued for 5 minutes. Intravenously administered metoprolol resulted in a higher peak plasma concentration of metoprolol (382 +/- 52 nmol/l) than coronary sinus retroinfusion (276 +/- 47 nmol/l). The nonischemic myocardial metoprolol concentration was of similar magnitude (393-454 pmol/g), whether infused IV or into the coronary sinus. Coronary sinus retroinfusion, however, resulted in a substantial accumulation of metoprolol in the ischemic myocardium (2887-5863 pmol/g). Coronary sinus retroinfusion resulted in a pronounced and specific accumulation in the ischemic myocardium in the territory of the LCX coronary artery.