Melagatran attenuates fibrin and platelet deposition in a porcine coronary artery over-stretch injury model.
Melagatran is the active form of the oral direct thrombin inhibitor, ximelagatran. The purpose of this study was to compare the effects of different doses of melagatran with heparin or placebo on platelet deposition and relative fibrin content after coronary angioplasty in pigs. After 125I-labelled fibrinogen and autologous 111Indium-labelled platelets had been infused a balloon injury was performed in the left anterior descending and the right coronary arteries. Pigs were randomized to receive either heparin 200 IU/kg bolus plus 20 IU/kg per h infusion (n = 7); melagatran 1 mg/kg bolus plus 0.33 mg/kg per h infusion (n = 7); melagatran bolus 0.5 mg/kg plus 0.17 mg/kg per h infusion (n = 7); melagatran 0.15 mg/kg bolus plus 0.05 mg/kg per h infusion (n = 6) or saline (n = 4). Seventy-five minutes after the angioplasty, the pigs were euthanized and the injured vessel segments were measured in a gamma counter. Compared with placebo, platelet deposition and relative fibrin content were reduced after both heparin and melagatran, in the latter case with a dose-response relationship. Melagatran reduced platelet deposition and relative thrombus size in a dose-dependent manner when compared with placebo after coronary angioplasty in pigs. No statistically significant difference between melagatran and heparin was found.
Scherstén
Fredrik
F
Department of Cardiology, Sahlgren University Hospital, Göteborg, Sweden. fredrik.schersten@telia.com
Wahlund
Göran
G
Björnheden
Tom
T
Carlsson
Stefan
S
Mattsson
Christer
C
Grip
Lars
L
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000818:Animals; D001384:Azetidines; D001596:Benzylamines; D001792:Blood Platelets / Q000187:drug effects*; D003331:Coronary Vessels / Q000293:injuries*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005337:Fibrin / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D010973:Platelet Adhesiveness / Q000187:drug effects; D011849:Radioactive Tracers; D013552:Swine; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control
D001384:Azetidines; D001596:Benzylamines; D005343:Fibrinolytic Agents; D011849:Radioactive Tracers; C109573:melagatran; D005337:Fibrin; D005998:Glycine