Platelet and fibrin deposition on coronary stents in minipigs: effect of hirudin versus heparin.
OBJECTIVE
The present study was designed to test the hypothesis that the direct thrombin hirudin is more efficient than heparin in reducing thrombus formation after coronary stenting.


BACKGROUND
Despite aggressive anticoagulation, subacute thrombosis of coronary stents is a major complication associated with these new devices.


METHODS
In 19 minipigs indium-111-labeled thrombocytes and iodine-125-labeled fibrinogen were injected 14 to 19 h before coronary implantation of tantalum balloon-expandable stents. In group 1 (n = 6, seven stents), a bolus of heparin (100 U/kg body weight) was given before stenting. Group 2 (n = 6, 11 stents) received both dextran (500 ml) and heparin (a 100-U/kg bolus followed by a continuous infusion of 50 U/kg per h). In group 3 (n = 7, 13 stents), hirudin (recombinant desulphatohirudin HV 1 [CGP 39393] [1 mg/kg]) was given before stent implantation, followed by an infusion of 1 mg/kg per h. All animals were pretreated with aspirin (250 mg intravenously).


RESULTS
Activated partial thromboplastin time was prolonged to > 1.8 times control values in groups 2 and 3. Histologic examination after perfusion fixation 12 h after stenting showed a variable extent of thrombus on all stents. Medial tear was observed in three stents in group 1, six stents in group 2 and six stents in group 3. The number of platelets on all stents averaged 116.2 (range 22 to 522) x 10(6) in group 1, 64.3 (range 11 to 169) x 10(6) in group 2 and 19.7 (range 9 to 38) x 10(6) in group 3 (p < 0.05 vs. group 1 and vs. group 2). The increase in platelet deposition, associated with medial tear in all groups, was lowest in the hirudin group. Similarly, fibrin deposition was lowest on stents in hirudin-treated animals.


CONCLUSIONS
Recombinant hirudin significantly reduces platelet and fibrin deposition on coronary stents compared with the reduction achieved with combined heparin, dextran and aspirin.
Buchwald
A B
AB
Department of Cardiology, University Clinic, Göttingen, Germany.
Sandrock
D
D
Unterberg
C
C
Ebbecke
M
M
Nebendahl
K
K
Lüders
S
S
Munz
D L
DL
Wiegand
V
V
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D001241:Aspirin / Q000627:therapeutic use; D003328:Coronary Thrombosis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D003911:Dextrans / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D005260:Female; D005337:Fibrin / Q000187:drug effects*; D006493:Heparin / Q000627:therapeutic use*; D024764:Hirudin Therapy; D006629:Hirudins / Q000031:analogs & derivatives*; D007205:Indium Radioisotopes; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D011994:Recombinant Proteins / Q000627:therapeutic use; D015607:Stents; D013552:Swine; D013556:Swine, Miniature / Q000097:blood*; D013997:Time Factors
D003911:Dextrans; D006629:Hirudins; D007205:Indium Radioisotopes; D011994:Recombinant Proteins; D005337:Fibrin; D006493:Heparin; D001241:Aspirin; C060225:desirudin