Effect of Antithrombotic Agents after Carotid Endarterectomy in Rats

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Abstract
The pharmacological prevention of thrombosis after surgical arterial injury is still an open question. In the present study, a recently developed model of carotid endarterectomy in rats was used to assess the effectiveness of heparin, prostacyclin (PGI2), and OKY-1581, a selective thromboxane A2 (TXA2) synthetase inhibitor, in preventing thrombus formation. Thirty-six male Sprague-Dawley rats were divided into six groups: A--controls (no treatment), B--tris (hydroxymethyl) aminomethane (Tris)-HCl buffer (vehicle of PGI2), C--heparin (100 IU/kg), D--OKY-1581 (100 microns/kg/minute), E--low dose PGI2 (10 ng/kg/minute), F--high dose PGI2 (50 ng/kg/minute). The animals were killed by in vivo perfusion-fixation 15 minutes after recirculation. The endarterectomized vessels were submitted to scanning electron microscopy examination and were evaluated blindly according to the following scale: 1, (almost) normal appearance of the endarterectomized surface; 2, moderately abnormal appearance; and 3, definitely abnormal appearance. The results in terms of thrombus prevention were as follows: controls congruent to Tris-HCl buffer less than OKY-1581 congruent to low dose PGI2 less than high dose PGI2 less than heparin. When combined, the two control groups did significantly worse than all four treated groups (P greater than 0.05). Fisher's exact test showed a statistically significant difference between controls and the heparin group (P = 0.01) and between controls and high dose PGI2-treated rats (P less than 0.05), but not between controls and low dose PGI2-(P less than 0.16) or OKY-1581-treated animals (P less than 0.16). In conclusion, the present study confirms that anticoagulation with heparin is effective in reducing thrombus formation after carotid endarterectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

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