Effect of tadalafil on neointimal hyperplasia in a rabbit carotid artery anastomosis model.
OBJECTIVE
Intimal thickening, which results from the response to arterial damage caused by therapeutic interventions or other reasons, is usually called as neointima. Neointimal hyperplasia is a main step in the pathogenesis of late-term restenosis, which is developed after vascular interventions. Reduction in nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling plays a substantial role in the pathogenesis of neointima formation. Phosphodiesterase V is detected in the peripheral coronary and pulmonary vascular smooth muscle cells and in the cardiac tissue. Based on the effects of phosphodiesterase V inhibitors on vascular smooth muscle cells, in the present study, the effect of tadalafil, a new member of phosphodiesterase V inhibitors, on neointimal hyperplasia was investigated in the rabbit carotid artery anastomosis model.


METHODS
Fourteen male New Zealand white rabbits weighing between 2.5-3 kg, were used. The rabbits were randomly divided into two equal groups; tadalafil group received oral tadalafil (2 mg/kg/day), and PBS group received sterile PBS solution (normal saline; 2 mg/kg/day) for 28 days after the surgery. The right carotid arteries of all rabbits were anastomosed in an end-to-end fashion using 8/0 polypropylene suture. The rabbits were sacrificed at the end of the postoperative period of 28 days. After sacrificing, firstly anastomosis segment on the right carotid artery and secondly a part of the left carotid artery (as control) of each rabbit were removed. Morphometric examination of tissue sections was performed under a light microscope connected to an image capture system.


RESULTS
There was a significant difference between the right and left carotid arteries in terms of intimal area and intima/media ratio both in tadalafil and PBS groups (p <0.001 for each). Intimal area and intima/media ratio were increased in the right carotid arteries compared to the left carotid arteries (p <0.001 for each). Besides, when the right carotid arteries of both groups were compared using covariance analysis, it was observed that intimal area and intima/media ratio in the anastomosis site were significantly reduced with tadalafil treatment (p <0.001).


CONCLUSIONS
The present study was promising in terms of tadalafil use as a new agent for the prevention of neointimal hyperplasia, which is the leading cause of late-term graft failure in vascular surgery.
Izmir University Faculty of Medicine, Department of Cardiovas cular Surgery, Izmir, Turkey.
Mehmet
M
Guzeloglu
Koray
K
Aykut
Gökhan
G
Albayrak
Soner
S
Atmaca
Suleyman
S
Oktar
Alper
A
Bagriyanik
Eyup
E
Hazan
D000714:Anastomosis, Surgical; D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D006965:Hyperplasia / Q000473:pathology / Q000517:prevention & control; D008297:Male; D008953:Models, Anatomic; D058426:Neointima / Q000473:pathology* / Q000517:prevention & control; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D000068581:Tadalafil; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
D002243:Carbolines; D058986:Phosphodiesterase 5 Inhibitors; D000068581:Tadalafil