Reduced intimal hyperplasia in rabbits via medical therapy after carotid venous bypass

Abstract

Intimal hyperplasia is a major cause of restenosis after the interventional or surgical treatment of occlusive arterial disease. We investigated the effects of clopidogrel, calcium dobesilate, nebivolol, and atorvastatin on the development of intimal hyperplasia in rabbits after carotid venous bypass surgery. We divided 40 male New Zealand rabbits into 4 study groups and 1 control group. After occluding the carotid arteries of the rabbits, we constructed jugular venous grafts between the proximal and the distal segments of the occluded artery. Thereafter, group 1 (control) received no medication. We administered daily oral doses of clopidogrel to group 2, calcium dobesilate to group 3, nebivolol to group 4, and atorvastatin to group 5. The rabbits were killed 28 days postoperatively. The arterialized jugular venous grafts were extracted for histopathologic examination. Intimal thicknesses were 42.87 +/- 6.95 microm (group 2), 46.5 +/- 9.02 microm (group 3), 34.12 +/- 5.64 microm (group 4), and 48.37 +/- 6.16 microm (group 5), all significantly less than the 95.12 +/- 9.93 microm in group 1 (all P < 0.001). Medial thicknesses were 94 +/- 6 microm (group 2), 101.5 +/- 13.52 microm (group 3), 90.5 +/- 9.69 microm (group 4), and 101.37 +/- 7.99 microm (group 5), all significantly thinner than the 126.62 +/- 13.53 microm in group 1 (all P < 0.001). In our experimental model of carotid venous bypass grafting in rabbits, clopidogrel, calcium dobesilate, nebivolol, and atorvastatin each effectively reduced the development of intimal hyperplasia. Herein, we discuss our findings and review the medical literature.

Keywords: Anastomosis, surgical; cardiovascular agents/administration & dosage; carotid arteries/drug/effects/pathology/surgery; carotid stenosis/prevention & control; coronary artery disease/drug therapy/prevention & control; coronary restenosis/drug therapy; disease models, animal; hyperplasia/drug therapy/etiology/prevention & control; jugular veins/transplantation; rabbits; tunica intima/drug effects/pathology.

Fig. 1 Operative photograph of completed venous bypass graft (arrow) to the internal carotid artery

Fig. 2 Postoperative carotid angiogram (arrow indicates venous bypass graft).

Fig. 3 Histologic views of the explanted grafts at the end of the study. Lesser intimal hyperplasia can be seen in all of the study groups in the A) control group: B) clopidogrel group, C) calcium dobesilate group, D) nebivolol group, and E) atorvastatin group (H & E, orig. ×10). a = adventitia; i = intima; m = media; arrows indicate borders of intimal and medial areas