Prevention of rethrombosis after coronary thrombolysis in a chronic canine model. II. Adjunctive therapy with r-hirudin.

Abstract

We examined the effectiveness of the direct-acting thrombin inhibitor, recombinant hirudin (r-hirudin), for prevention of coronary rethrombosis after thrombolysis with recombinant tissue plasminogen activator (rt-PA) in a canine model of coronary artery thrombosis. The reocclusion rate of 15-30% associated with thrombolytic therapy emphasizes the need for adjunctive therapy to prevent rethrombosis. We studied r-hirudin for its potential to prevent reocclusion in a model of coronary artery thrombosis/thrombolysis. The circumflex coronary arteries of anesthetized dogs were instrumented with a flow probe, an intraluminal electrode, and a ligature stenosis. The dogs were reanesthetized on the ninth postoperative day, and intimal injury was induced with an anodal current. After occlusive thrombus formation, tissue plasminogen activator (rt-PA) was administered. The animals were allocated to receive either placebo, r-hirudin [5 mg/kg intravenously (i.v.) bolus, 2 mg/kg/h i.v., for 3.5 h] or r-hirudin (5 mg/kg i.v., bolus, 1 mg/kg/h i.v., for 12 h). Neither aspirin nor heparin was used. Ex vivo platelet function and coronary artery blood flow velocity were recorded on each of 5 consecutive days. Infarct size and residual thrombus weight were determined at the end of the protocol. r-Hirudin infusion (3.5 and 12 h) provided little benefit over rt-PA alone. Ex vivo platelet aggregation was not affected by r-hirudin. Little improvement in the incidence of reocclusion and mortality in a model of coronary artery thrombosis/thrombolysis resulted from adjunctive treatment with r-hirudin.

• Authors: W E Rote, D X Mu, E R Bates, M A Nedelman, B R Lucchesi
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 23 Issue 2 Pg. 203-11 (Feb 1994) ISSN: 0160-2446 [Print] United States
• PMID: 7511748 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Fibrinolytic Agents
• Recombinant Proteins
• Tissue Plasminogen Activator

Topics

• Animals
• Blood Coagulation (drug effects)
• Chronic Disease
• Coronary Thrombosis (pathology, physiopathology, prevention & control)
• Coronary Vessels (pathology, physiopathology)
• Dogs
• Fibrinolytic Agents (therapeutic use)
• Hirudin Therapy
• Male
• Myocardial Infarction (pathology, physiopathology)
• Platelet Aggregation (drug effects)
• Recombinant Proteins (therapeutic use)
• Recurrence
• Time Factors
• Tissue Plasminogen Activator (therapeutic use)