Effects of thrombin inhibition on the development of acute platelet-thrombus deposition during angioplasty in pigs. Heparin versus recombinant hirudin, a specific thrombin inhibitor

M. Heras, J. H. Chesebro, W. J. Penny, K. R. Bailey, L. Badimon, V. Fuster

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Abstract

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 1mg/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 fibrogen 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 fibrogen. In contrast, the deposition of platelets and fibrinogen in subendothelial injury was very low and independent of the heparin administered. Macroscopic thrombus decreased from 72% of deeply injured arterial segments in the lowest heparin dosage group (activated partial thromboplastin time similar to the animals in the hirudin group) to 10% in the highest heparin dosage group and to 0% in the animals treated with hirudin. Activated partial thromboplastin times were threefold that of control basal values for animals on the lowest heparin dosage (35 units/kg); a similar prolongation of times was observed in the hirudin group. However, the mean logs of platelet and fibrinogen deposition per centimeter squared of deep injury were significantly lower in the hirudin group than on 35 units/kg heparin (3.23 ± 0.44 vs. 5.44 ± 0.60 and 3.98 ± 0.36 vs. 5.33 ± 0.53, respectively; p < 0.001) and were also lower in the hirudin group than on the highest dosage (250 units/kg) of heparin (3.8 ± 0.6 and 4.6 ± 0.6, respectively; p < 0.04). In the presence of deep but not subendothelial arterial injury after angioplasty, there is a dose-dependent inhibition by heparin of acute platelet and fibrinogen depositions and the proportion of arterial segments with mural thrombosis. Hirudin was more effective in preventing thrombosis than heparin; this probably reflects the more specific and potent inhibition of thrombin by hirudin.

Original languageEnglish (US)
Pages (from-to)657-665
Number of pages9
JournalCirculation
Volume79
Issue number3
DOIs
StatePublished - Jan 1 1989

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ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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