Pharmacokinetic analysis of coronary sinus retroinfusion in pigs |
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Authors: | Nobuo Hatori Per-Ove Sjöquist Carl Regårdh Lars Rydén |
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Institution: | (1) National Defense Medical College, Saitana, Japan;(2) Hässle Research Laboratories, Möndal, Sweden;(3) Department of Cardiology, Karolinska Institute, Stockholm;(4) Thoraxklinikerna, Karolinska Sjukhuset, S-10401 Stockholm, Sweden |
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Abstract: | Summary 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 starded 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. |
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Keywords: | coronary sinus left circumflex coronary artery retroinfusion metoprolol |
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