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.
Hatori
N
N
National Defense Medical College, Saitana, Japan.
Sjöquist
P O
PO
Regårdh
C
C
Rydén
L
L
D000818:Animals; D003327:Coronary Disease / Q000378:metabolism*; D003331:Coronary Vessels / Q000502:physiology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D008790:Metoprolol / Q000097:blood / Q000493:pharmacokinetics*; D009206:Myocardium / Q000378:metabolism*; D013552:Swine; D014316:Tritium
D014316:Tritium; D008790:Metoprolol