Time course of thrombotic changes after microsurgical carotid endarterectomy in the rats.

An experimental model of microsurgical carotid endarterectomy in rats developed recently in our laboratory was used in the present study. Our adult Sprague-Dawley rats were killed by in vivo perfusion-fixation at 5 minutes, 15 minutes, 30 minutes, 3 hours, 1 day, and 3 days after the completion of carotid endarterectomy, and vessels were studied by scanning electron microscopy, light microscopy, and transmission electron microscopy for evaluation of thrombotic changes at the level of arterial injury. Although no postoperative carotid occlusion was observed, thrombus formation was noted as early as 15 minutes after recirculation. Thrombus formation reached its peak at 3 hours and was no longer detected 3 days after the procedure. Microsurgical carotid endarterectomy in rats may be a useful experimental model for the evaluation of antithrombotic drugs

Carotid endarterectomy in rats. Technical note.

Carotid endarterectomy in rats. Technical note. Carotid endarterectomy is a widely used surgical procedure for stroke-threatened patients. Thrombosis is a major post-operative risk and appears to occur very early after operation is completed. Several drugs may influence the mechanism of thrombus formation, and theoretically could be considered for perioperative use in clinical cases. Therefore, inexpensive easily reproducible experimental models would be useful. This paper describes microsurgical carotid endarterectomy in the rat

Time course of thrombotic changes after microsurgical carotid endarterectomy in the rats.

An experimental model of microsurgical carotid endarterectomy in rats developed recently in our laboratory was used in the present study. Our adult Sprague-Dawley rats were killed by in vivo perfusion-fixation at 5 minutes, 15 minutes, 30 minutes, 3 hours, 1 day, and 3 days after the completion of carotid endarterectomy, and vessels were studied by scanning electron microscopy, light microscopy, and transmission electron microscopy for evaluation of thrombotic changes at the level of arterial injury. Although no postoperative carotid occlusion was observed, thrombus formation was noted as early as 15 minutes after recirculation. Thrombus formation reached its peak at 3 hours and was no longer detected 3 days after the procedure. Microsurgical carotid endarterectomy in rats may be a useful experimental model for the evaluation of antithrombotic drugs

Effect of antithrombotic agents after carotid endarterectomy in rats

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

Effect of antithrombotic agents after carotid endarterectomy in rats

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

Microsurgical carotid endarterectomy in rats

The purpose of this study was to develop an inexpensive experimental model of carotid endarterectomy. Unilateral common carotid endarterectomies 3 mm in length were performed on 25 rats using microsurgical techniques. The pattern of endothelial regrowth after endarterectomy, the pinocytosis of regenerated endothelial cells, and the effects of heparin and thromboxane A2 synthetase inhibitor on thrombus formation were examined 7 days after the resumption of flow. Pinocytotic vesicular transport in endothelial cells was evaluated using horseradish peroxidase. All endarterectomized vessels in both control and drug-treated groups were patent 7 days after operation without apparent mural thrombus formation. Regenerated endothelial cells had spindle-shaped nuclei and cell bodies with long axes oriented parallel to the direction of blood flow. There were several instances where the leading edge of the endothelium at the distal end was reflected back in the distal direction. The extent of the endothelial ingrowth was often greater from the proximal end of the endarterectomy than from the distal end. These observations suggest that hemodynamic force affects endothelial regeneration. Pinocytotic activity was less in the regenerated endothelium than in either the endothelium remaining at the periphery of the endarterectomy or the endothelium of the control animals