Effects of thrombin inhibition on the development of acute platelet-thrombus deposition during angioplasty in pigs. Heparin versus recombinant hirudin, a specific thrombin inhibitor.
The effect of recombinant hirudin and the dosage of heparin on acute platelet-thrombus deposition during carotid angioplasty in anesthetized pigs was prospectively assessed. Fifty-five animals (mean weight, 33.9 kg) were randomized to one of six heparin dosages: heparin boluses of 35, 50, 100, 150, 200, or 250 units/kg followed by a continuous infusion of 35, 50, 100, 150, 200, or 250 units/kg/hr, respectively. Another five pigs received a bolus of 1 mg/kg hirudin (recombinant desulphatohirudin), a specific thrombin inhibitor, followed by an infusion of 1 mg/kg/hr. Bilateral carotid angioplasty was performed in all pigs 20 minutes after starting the infusion; they were sacrificed 57 +/- 12 minutes after the procedure. Deep medial arterial injury was present in approximately 75% of the dilated segments, and subendothelial injury in the remaining 25%. Mean log of number of platelets and molecules of fibrinogen per centimeter squared of deep injury in segments from all the animals treated with heparin were 4.74 +/- 1.03 and 5.02 +/- 0.64, respectively. A regression analysis showed an inverse correlation of the log of platelet deposition with the heparin group (r = -0.56, p = 0.0001) with administered total units of heparin (r = -0.55, p = 0.0003) and with mean plasma heparin concentration (r = -0.55, p = 0.0004) in deeply injured arteries. Similar inverse relations were obtained for fibrinogen. In contrast, the deposition of platelets and fibrinogen in subendothelial injury was very low and independent of the heparin administered.(ABSTRACT TRUNCATED AT 250 WORDS)
Heras
M
M
Division of Cardiovascular Disease and Internal Medicine, Mayo Clinic.
Chesebro
J H
JH
Penny
W J
WJ
Bailey
K R
KR
Badimon
L
L
Fuster
V
V
D000800:Angioplasty, Balloon; D000818:Animals; D002339:Carotid Arteries; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006493:Heparin / Q000627:therapeutic use*; D024764:Hirudin Therapy; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D011994:Recombinant Proteins / Q000627:therapeutic use; D013552:Swine; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000517:prevention & control*
D011994:Recombinant Proteins; D005340:Fibrinogen; D006493:Heparin; D013917:Thrombin