在犬冠状动脉血栓形成闭塞后，早期静脉注射美托洛尔可通过重组组织型纤溶酶原激活剂溶栓，改善梗死危险区的侧支血流，从而增强心肌挽救。

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.

作者信息

Zmudka K, Aubert A, Dubiel J, Vanhaecke J, Flameng W, Kaczmarek J, De Geest H

机构信息

Second Department of Cardiology, Academy of Medicine, Kraków, Poland.

出版信息

J Am Coll Cardiol. 1994 May;23(6):1499-504. doi: 10.1016/0735-1097(94)90398-0.

DOI:10.1016/0735-1097(94)90398-0

PMID:8176113

Abstract

OBJECTIVES

We studied the effects of beta 1-adrenergic blockade preceding thrombolysis on hemodynamic variables, myocardial blood flow and infarct size in a canine model of thrombotic occlusion of the left anterior descending coronary artery.

BACKGROUND

Previous work suggested a reduction in infarct size and improvement in left ventricular function by intravenous beta-blockade preceding thrombolysis.

METHODS

Experiments were conducted in 34 anesthetized dogs; 17 received 0.975 mg/kg body weight of metoprolol intravenously starting 15 min after occlusion, and thrombolysis was initiated 60 min after occlusion. Seventeen dogs received saline solution followed by thrombolysis. Coronary blood flow was measured by radioactive microspheres, infarct size by a dye method, hemodynamic variables by catheter-tipped pressure transducers and 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 flow and hemodynamic variables were similar. Sixty minutes 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. Collateral flow 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 (14.30 +/- 8.63 vs. 7.35 +/- 4.94) and endocardial (13.18 +/- 8.21 vs. 6.26 +/- 5.34 cm3/min per 100 g) layers was higher (p < or = 0.05) in the metoprolol-treated dogs. The ratio of epicardial flow area at risk/circumflex territory was inversely correlated to infarct size (r = -0.69, p < 0.01). After 5 min of occlusion, collateral flow was comparable in the five dogs of each group; over the next 55 min it remained constant in the metoprolol group but decreased in the placebo dogs.

CONCLUSIONS

Intravenous metoprolol, administered before thrombolysis, enhances infarct size limitation, partly by improvement of collateral flow to area at risk.

摘要

目的

我们在犬左前降支冠状动脉血栓闭塞模型中研究了溶栓前β1肾上腺素能阻滞剂对血流动力学变量、心肌血流量和梗死面积的影响。

背景

先前的研究表明，溶栓前静脉注射β受体阻滞剂可减小梗死面积并改善左心室功能。

方法

对34只麻醉犬进行实验；17只在闭塞后15分钟开始静脉注射0.975mg/kg体重的美托洛尔，并在闭塞后60分钟开始溶栓。17只犬接受生理盐水然后进行溶栓。通过放射性微球测量冠状动脉血流量，通过染料法测量梗死面积，通过导管尖端压力传感器测量血流动力学变量，通过热稀释法测量心输出量。

结果

美托洛尔治疗组和安慰剂治疗组的梗死面积分别为危险区域面积的23.62±18.04%和41.50±16.03%（p<0.01）。闭塞前，心肌血流量和血流动力学变量相似。闭塞后60分钟，美托洛尔治疗组的心输出量较低（1.94±0.41对2.32±0.68升/分钟，p<0.01）。美托洛尔治疗组中，流向危险区域的侧支血流（17.27±7.44对10.25±5.33）及其心外膜（21.68±8.04对11.5±6.10）、心肌中层（14.30±8.63对7.35±4.94）和心内膜（13.18±8.21对6.26±5.34cm³/分钟每100克）层的血流较高（p≤0.05）。危险区域心外膜血流面积/回旋支区域的比值与梗死面积呈负相关（r=-0.69，p<0.01）。闭塞5分钟后，每组的5只犬的侧支血流相当；在接下来的55分钟内，美托洛尔组保持不变，而安慰剂组的犬侧支血流减少。