INTRAVENOUS METOPROLOL PRECEDING THROMBOLYSIS IN ACUTE THROMBOTIC MYOCARDIAL-INFARCTION IN THE DOG - EFFECTS ON INFARCT SIZE, MYOCARDIAL BLOOD-FLOW, AND LEFT-VENTRICULAR FUNCTION

Intravenous (i.v.) metoprolol preceding thrombolysis in an anesthetize d dog model of thrombotic occlusion of the anterior descending coronar y artery helps limit infarct size (IS). We wished to determine whether these effects are caused at least in part by enhancement of collatera l blood flow to the area at risk (AAR). Thrombotic occlusion was provo ked by a copper coil technique. We measured intracardiac pressures and their derivatives by catheter-tip micromanometers, cardiac output (CO ) by thermodilution method, regional myocardial blood flow (RMBF) by r adioactive microspheres technique, global and regional left ventricula r (LV) function by ventriculography, and IS with triphenyltetrazolium at the end of the experiment. Measurements were performed before and a fter 60-min occlusion and after 30- and 90-min reperfusion. Received f ifteen minutes after occlusion, 12 dogs metoprolol 0.3 mg/kg i.v. foll owed by 0.3 mg/kg/h; 12 received saline. Thrombolysis was performed in all dogs after 60-min occlusion with recombinant tissue-type plasmino gen activator (rt-PA) 10 mu g/kg/min for 30 min. Hemodynamic findings were similar in both groups. During occlusion, collateral flow to tota l AAR (18.6 +/- 7.5 vs. 11.0 +/- 6.1 ml/min/100 g), to its subepicardi al (22.1 +/- 8.1 vs. 12.2 +/- 7.2 ml/min/100 g), midmyocardial (16.0 /- 8.9 vs. 8.0 +/- 5.5 ml/min/100 g), and endocardial(l4.1 +/- 8.1 vs. 7.3 +/- 6.0 ml/min/100 g) layers was higher (p less than or equal to 0.03) in metoprolol than in placebo-treated dogs. The ratio of flow of AAR/circumflex region was higher (p less than or equal to 0.03) for t otal area (0.39 +/- 0.14 vs. 0.23 +/- 0.12), epicardial(0.55 +/- 0.19 VS. 0.34 +/- 0.21 ml/min/100 g) and midmyocardial (0.30 +/- 0.16 vs. 0 .17) layers. Global ventricular function was comparable in both groups after 90-min reperfusion; the infarct region was akinetic in the meto prolol group and dyskinetic in the placebo group. AAR (41.1 +/- 15.3 v s. 42.4 +/- 12.9 cm(2)) was similar in both groups, and IS (21.6 +/- 2 0.7 vs. 43.0 +/- 17.3% of AAR, p = 0.014) was smaller in metoprolol-tr eated dogs. Metoprolol administered i.v. before thrombolysis enhances collateral blood flow to the AAR, limits IS, and improves regional LV performance.