title: Antithrombotic therapy for deep arterial injury by angioplasty. Efficacy of common platelet inhibition compared with thrombin inhibition in pigs.
abstract: BACKGROUND
  Platelet-thrombus formation is a complication of arterial wall deep injury by balloon angioplasty that may lead to acute arterial occlusion and may contribute to restenosis.
  
  
  RESULTS
  Because common platelet-inhibitor drugs with a heparin bolus (100 units/kg) may be effective in inhibiting platelet-thrombus formation after arterial angioplasty, these were compared with a bolus of heparin alone (control), the specific thrombin inhibitor hirudin (1.0 mg/kg), and saline (hirudin control) in normal pigs after angioplasty of the common carotid arteries. In the presence of deep arterial wall injury (injury exposing the media), indium-111-labeled platelet deposition (x 10(6)/cm2) was 68.8 +/- 12.3 and 48.1 +/- 16.9 in the control animals. This was significantly reduced by pretreatment with low-dose aspirin (1 mg/kg/day), by high-dose aspirin (20 mg/kg/day) plus dipyridamole, and especially by thrombin inhibition with hirudin. Treatment regimens with aspirin alone (20 mg/kg/day), dipyridamole alone, or sulfinpyrazone were ineffective. Likewise, the incidence of mural thrombosis was 75% and 80% in deeply injured arteries of controls and was significantly reduced to 46% with aspirin plus dipyridamole, 25% with low-dose aspirin, and 0% with hirudin. The incidence of mural thrombosis was unchanged with high-dose aspirin (69%), dipyridamole (90%), or sulfinpyrazone (92%). This mural thrombosis could not be identified by angiography. In the presence of mild injury (deendothelialization), platelet deposition was low (less than 10 x 10(6)/cm2, a single layer) and was not changed by any therapy, including hirudin.
  
  
  CONCLUSIONS
  These therapies do not affect platelet adhesion to deeply or mildly injured artery. These data suggest a greater role for thrombin inhibition than with thromboxane or cyclooxygenase inhibition in the pathogenesis of platelet-rich mural thrombosis after deep injury during angioplasty. Antithrombotic therapy for arterial thrombosis by thrombin inhibition appears promising.
authors.affiliation: Division of Cardiovascular Disease and Internal Medicine, Mayo Clinic, Rochester, MN 55905.
authors.forename: J Y
authors.initials: JY
authors.lastname: Lam
authors.forename: J H
authors.initials: JH
authors.lastname: Chesebro
authors.forename: P M
authors.initials: PM
authors.lastname: Steele
authors.forename: M
authors.initials: M
authors.lastname: Heras
authors.forename: M W
authors.initials: MW
authors.lastname: Webster
authors.forename: L
authors.initials: L
authors.lastname: Badimon
authors.forename: V
authors.initials: V
authors.lastname: Fuster
mesh_terms: D000800:Angioplasty, Balloon; D000818:Animals; D001158:Arteries / Q000293:injuries* / Q000473:pathology; D001241:Aspirin / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006331:Heart Diseases / Q000503:physiopathology; D006493:Heparin / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013552:Swine; D013927:Thrombosis / Q000503:physiopathology
chemical_list: D005343:Fibrinolytic Agents; D006629:Hirudins; D010975:Platelet Aggregation Inhibitors; D004176:Dipyridamole; D006493:Heparin; D001241:Aspirin