Inability of Metoprolol to Achieve a Sustained Limitation of Infarct Size 24 h After Coronary Artery Embolization in the Closed Chest Dog

Abstract

Summary: Studies were undertaken to ascertain whether metoprolol, a β1-selective adrenergic blocking agent, could offer a limitation of myocardial injury throughout a 24-h period of coronary embolization in the dog. Regional myocardial ischaemia was induced through the use of a bead embolization technique which did not require thoracotomy. In order to delineate the zone at risk of infarction (hypoperfused area), radioactive microspheres (141Ce) were administered intraventricularly immediately after embolization. In the drug-treated group (n = 8) metoprolol administration was initiated by an intravenous bolus injection (0.3 mg · kg-1). This was followed by a continuous infusion (0.003 mg · kg-1 · min-1) during the 24-h experimental period. In the control group (n = 8) saline was administered throughout the 24-h period. Electrocardiographic activity was monitored throughout the experiment and this confirmed the negative chronotropic and antiarrhythmic properties of metoprolol. After 24 h, the hearts were excised and transverse myocardial sections (3 mm) prepared. Areas of necrosis were visualized by tetrazolium staining and risk zones were defined by microsphere autoradiography. In the control and metoprolol-treated groups, 73.3 ± 7.7% and 68.2 ± 6.1% of the risk zone became necrotic, respectively. There was no significant difference between these groups.