Hirudin, heparin, and placebo during deep arterial injury in the pig. The in vivo role of thrombin in platelet-mediated thrombosis.
Three dosages (0.3, 0.7, and 1.0 mg/kg) of recombinant hirudin, a specific inhibitor of thrombin, were compared with heparin (50 units/kg) and placebo for reducing thrombus formation in the carotid arteries of 50 pigs after deep injury by balloon dilatation. Each drug was administered as a bolus followed immediately by a continuous infusion of the same dose per hour. Major end points were quantitative indium-111-labeled platelet and iodine-125-labeled fibrinogen deposition and the incidence of mural thrombosis. This study showed that heparin, at a dose that prolonged the activated partial thromboplastin time (APTT) to twice the control time, did not prevent mural thrombosis or significantly reduce platelet deposition compared with placebo but did reduce fibrinogen deposition. Recombinant hirudin markedly reduced platelet and fibrinogen deposition in a dose-related manner and totally eliminated mural thrombosis at an APTT of two to three times that of control. Platelet deposition (x 10(6)/cm2, mean +/- SEM) in areas of deep arterial injury for the placebo, heparin, and 0.3, 0.7, and 1.0 mg/kg hirudin groups was 54 +/- 21, 33 +/- 9, 22 +/- 6, 8 +/- 1, and 7 +/- 1, respectively; electron microscopy showed a single layer (or less) of platelets at the two highest hirudin dosages. The incidence of macroscopic mural thrombosis was 76% with placebo, 57% with heparin, 46% with 0.3 mg/kg hirudin; there were no thrombi with 0.7 or 1.0 mg/kg hirudin (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Heras
M
M
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905.
Chesebro
J H
JH
Webster
M W
MW
Mruk
J S
JS
Grill
D E
DE
Penny
W J
WJ
Bowie
E J
EJ
Badimon
L
L
Fuster
V
V
D000818:Animals; D002339:Carotid Arteries / Q000648:ultrastructure; D020212:Carotid Artery Injuries; D002404:Catheterization; D004305:Dose-Response Relationship, Drug; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D006629:Hirudins / Q000494:pharmacology*; D008297:Male; D008855:Microscopy, Electron, Scanning; D010314:Partial Thromboplastin Time; D010919:Placebos; D010974:Platelet Aggregation; D013552:Swine; D013917:Thrombin / Q000502:physiology*; D013927:Thrombosis / Q000188:drug therapy / Q000503:physiopathology
D006629:Hirudins; D010919:Placebos; D005340:Fibrinogen; D006493:Heparin; D013917:Thrombin