PRONOUNCED ACCUMULATION OF METOPROLOL IN ISCHEMIC MYOCARDIUM AFTER CORONARY VENOUS RETROINFUSION

The myocardial availability of the β1-selective blocker metoprolol was compared following standard intravenous (i.v.) administration and after coronary venous retroinfusion. Thirteen open-chest farm pigs were subjected to 90-min occlusion of the left anterior descending coronary artery. In six of these pigs, metoprolol was ad-ministered as an i.v. injection while 7 pigs received the drug retrogradely into the coronary vein. The time of ad-ministration was 5 min. In both groups, metoprolol was administered after 30 min of coronary artery occlusion. Metoprolol did not influence heart rate (HR) or blood pressure (BP) whether administered i.v. or into the coronary vein. At the end of administration, plasma metoprolol was significantly higher when administered i.v. (2,955 ± 543 nmol/L) than after coronary venous infusion (1,213 ± 464 nmol/L; p < 0.05). At 30 and 60 min after injection, plasma metoprolol did not differ significantly between the two groups. Myocardial tissue concentration of metoprolol in nonischemic myocardium was 480 pmol/g for both groups and similar in the subendocardial, midmyocardial, and subepicardial layers of the myocardium. After i.v. administration, myocardial Metoprolol concentration in the ischemic zone was less than that in the nonischemic zone, averaging 150-300 pmol/g tissue. In contrast, coronary venous retroinfusion of metoprolol resulted in a substantial accumulation of the drug in the ischemic zone, as exemplified by a subendocardial concentration of 2,002 ± 689; a midmyocardial concentration of 26,643 ± 8,813 and a subepicardial concentration of 98,571 ± 58,930 pmol/g, respectively (mean ± SE). Coronary venous retroinfusion of metoprolol resulted in a pronounced accumulation of drug in the ischemic myocardium. The transmyocardial concentration gradient was significant, with the highest levels in the subepicardial layers and the lowest in the subendocardial layers. These high concentrations of metoprolol were obtained without any adverse hemodynamic effects. © 1990 Raven Press, Ltd., New York.