EARLY INTRAVENOUS ADMINISTRATION OF METOPROLOL ENHANCES MYOCARDIAL SALVAGE BY THROMBOLYSIS WITH RECOMBINANT TISSUE-TYPE PLASMINOGEN-ACTIVATOR AFTER THROMBOTIC CORONARY-ARTERY OCCLUSION IN THE DOG BY IMPROVEMENT OF THE COLLATERAL BLOOD-FLOW TO THE AREA AT RISK

Objectives. We studied the effects of beta(1)-adrenergic blockade prec eding thrombolysis on hemodynamic variables, myocardial blood flow and infarct size in a canine model of thrombotic occlusion of the left an terior descending coronary artery. Background. Previous work suggested a reduction in infarct size and improvement in left ventricular funct ion by intravenous beta blockade preceding thrombolysis. Methods. Expe riments were conducted in 34 anesthetized dogs; 17 received 0.975 mg/k g body weight of metoprolol intravenously starting 15 min after occlus ion, and thrombolysis was initiated 60 min after occlusion. Seventeen dogs received saline solution followed by thrombolysis. Coronary blood how was measured by radioactive microspheres, infarct size by a dye m ethod, hemodynamic variables by catheter tipped pressure transducers a nd cardiac output by the thermodilution method. Results, Infarct size in metoprolol and placebo treated dogs was 23.62 +/- 18.04% and 41.50 +/- 16.03% of area at risk, respectively (p < 0.01). Before occlusion, myocardial blood dow and hemodynamic variables were similar. Sixty mi nutes after occlusion, cardiac output (1.94 +/- 0.41 vs. 2.32 +/- 0.68 liters/min, p < 0.01) was lower in the metoprolol treated dogs, Colla teral how to the area at risk (17.27 +/- 7.44 vs. 10.25 +/- 5.33) and to its epicardial(21.68 +/-: 8.04 vs. 11.5 +/- 6.10), midmyocardial (1 4.30 +/- 8.63 vs. 7.35 +/- 4.94) and endocardial (13.18 +/- 8.21 vs. 6 .26 +/- 5.34 cm(3)/min per 100 g) layers was higher (p less than or eq ual to 0.05) in the metoprolol-treated dogs. The ratio of epicardial f low area at risk/circumflex territory was inversely correlated to infa rct size (r = -0.69, p < 0.01). After 5 min of occlusion, collateral f low was comparable in the five dogs of each group; over the next 55 mi n it remained constant in the metoprolol group but decreased in the pl acebo dogs. Conclusions. Intravenous metoprolol, administered before t hrombolysis, enhances infarct size limitation, partly by improve ment of collateral how to area at risk.