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This Article Full Text Full Text (PDF) All Versions of this Article: 290/3/H959    most recent 00649.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Hong, T.-T. Articles by Lucchesi, B. R. Search for Related Content PubMed PubMed Citation Articles by Hong, T.-T. Articles by Lucchesi, B. R.

Effect of thrombolysis on myocardial injury: recombinant tissue plasminogen activator vs. alfimeprase

Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan

Submitted 16 June 2005 ; accepted in final form 25 September 2005

Plasmin-dependent thrombolytic agents are potentially prothrombotic and proinflammatory. Alfimeprase, a zinc-containing metalloproteinase, degrades fibrin directly and achieves thrombolysis independent of plasmin formation. This study examines the hypothesis that thrombolysis in the absence of plasmin generation results in improved myocardial salvage on reperfusion. The thrombolytic effects of recombinant tissue plasminogen activator [rt-PA; 0.022 mg/kg, 1/10 of which was administered as a loading dose; the rest (9/10) was infused over 60 min by intracoronary (ic) administration] or alfimeprase (0.5 mg/kg over 1 min ic) were evaluated in a canine model of arterial thrombosis involving electrolytic injury of the left circumflex (LCX) coronary artery. Both agents induced thrombolysis, with onset of reperfusion being more rapid after alfimeprase compared with rt-PA (1.5 ± 0.6 vs. 10.1 ± 2.1 min). In the absence of adjunctive therapy, time to reocclusion after alfimeprase was 3.2 ± 0.5 min compared with 77.5 ± 31.9 min with rt-PA. The glycoprotein IIb/IIIa platelet receptor antagonist CRL-42796 prolonged reperfusion time after thrombolysis with alfimeprase or rt-PA. The effect of each lytic agent on myocardial infarct size was examined in a separate group of dogs subjected to 60 min of LCX coronary artery ligation and 4 h of reperfusion. Myocardial infarct size, expressed as percentage of the risk region, was larger (32.16 ± 3.95%) after rt-PA compared with alfimeprase (19.85 ± 3.61%) or that of the saline control group (18.46 ± 3.34%). rt-PA in contrast to alfimeprase, a direct-acting fibrinolytic agent, is associated with an increase in myocyte reperfusion injury.

myocardium; reperfusion injury; thrombolytic agents