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.
OBJECTIVE
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.
Zmudka
K
K
Second Department of Cardiology, Academy of Medicine, Kraków, Poland.
Aubert
A
A
Dubiel
J
J
Vanhaecke
J
J
Flameng
W
W
Kaczmarek
J
J
De Geest
H
H
D000818:Animals; D003097:Collateral Circulation / Q000187:drug effects*; D003328:Coronary Thrombosis / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage*; D011897:Random Allocation; D011994:Recombinant Proteins / Q000627:therapeutic use; D016879:Salvage Therapy / Q000379:methods*; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; D008790:Metoprolol