Pronounced accumulation of metoprolol in ischemic myocardium after coronary venous retroinfusion.
The myocardial availability of the beta 1-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 administered as an i.v. injection while 7 pigs received the drug retrogradely into the coronary vein. The time of administration 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 less than 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 approximately 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
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Ryden
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Tadokoro
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Sjoquist
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Kar
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Ervik
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Corday
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D003331:Coronary Vessels; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D013552:Swine
D008790:Metoprolol