Thrombin inhibition enhances tissue-type plasminogen activator-induced thrombolysis and delays reocclusion

Am J Physiol. 1992 Feb;262(2 Pt 2):H374-9. doi: 10.1152/ajpheart.1992.262.2.H374.

Abstract

The objectives of this study were to test the hypotheses that thrombin inhibitors 1) enhance tissue-type plasminogen activator (t-PA)-induced coronary thrombolysis and 2) prevent or delay coronary artery reocclusion. Seventy-one dogs developed occlusive coronary thrombi after introducing a copper coil into the left anterior descending coronary artery (LAD). Coronary blood flows were monitored by an externally positioned pulsed Doppler flow probe. t-PA was given with or without heparin at different times after LAD occlusions. In some experiments, hirugen, a synthetic hirudin-based peptide and specific thrombin inhibitor, was given as 4 mg/kg i.v. bolus and 3 mg.kg-1.h-1 i.v. infusion at 30 min after LAD occlusion with t-PA and a bolus of heparin. Thrombolysis times were significantly shorter in t-PA- and heparin-treated dogs than in dogs treated with t-PA alone. Reocclusion times were significantly longer in t-PA- and heparin-treated dogs than in dogs treated with t-PA alone. Continuous heparin infusions prolonged reocclusion times to greater than 180 min in all treated dogs. The addition of hirugen to t-PA plus one bolus heparin prolonged reocclusion times to 90 +/- 6 min in dogs with 30-min thrombi. Thus heparin enhances t-PA-induced thrombolysis and delays reocclusion. Addition of a specific thrombin inhibitor, such as hirugen, to heparin enhances its effect on delaying reocclusion.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Coagulation / drug effects
  • Coronary Disease / prevention & control*
  • Dogs
  • Fibrinolytic Agents / pharmacology*
  • Heparin / pharmacology
  • Hirudins / analogs & derivatives
  • Hirudins / pharmacology
  • Peptide Fragments / pharmacology
  • Platelet Aggregation
  • Recurrence
  • Thrombin / antagonists & inhibitors*
  • Time Factors
  • Tissue Plasminogen Activator / pharmacology*

Substances

  • Fibrinolytic Agents
  • Hirudins
  • Peptide Fragments
  • hirugen
  • Heparin
  • Thrombin
  • Tissue Plasminogen Activator