The comparison of inhibitor effects of pentoxifylline and adenosine substances in anastomoses performed on rat carotid arteries on restenosis, development of neointima and smooth muscle cell proliferation

Objective: Cerebral ischemia and infarct are significant morbidity and mortality reasons at the present time. Therefore the revascularization to be done before development of infarct may be able to affect the degree of morbidity. However, as in other parts of the body, also in the brain, the long-term openness of vascular anastomoses and bypass grafts performed decreases with the development of intimal hyperplasia in the region that vascular injury occurs. Intimal hyperplasia and smooth muscle cell proliferation have a great impact on restenosis may be developed after vascular interventions. While pentoxifylline reduces collagen accumulation associated with vascular injury by inhibiting some cytokines, adenosine inhibits smooth muscle cell proliferation. Hence, we have searched and compared the inhibitor effects of pentoxifylline and adenosine substances on restenosis, development of neointima and smooth muscle cell proliferation in the anastomoses performed on rat carotid arteries. Material and Method: All anastomoses in the work have been performed by the same surgeon. In our work, randomly chosen, Sprague Dawley type, weighing in average 250-300 grams, male or female 24 rats were used. During the work, all rats were kept in the same place and under the same conditions ( 20 + 2 0C temperature, in a room which has air conditioning system and sun light). On the day of experiment, 80 mg/kg ketamine + 10 mg/kg xylazine was given as anesthesia. 45 minutes after the first dose, 40 mg/kg ketamine + 5 mg/kg xylazine was applied as the second dose of anesthesia. 50 mg/kg dose of cefazoline was preoperatively applied by intramuscular way as prophylactic to prevent infection. The operation field was cleaned with antiseptic solution. The subjects' right side carotid artery was used for anastomosis, and the left side carotid artery was used for controlling. After sterilization, the proper position was provided and the common carotid artery was explored by making a horizontal right side neck incision. Then the carotid artery was dissected, proximally and distally clamped with a microclamp. The same artery was transacted with a micro scissors, then, anastomosis was applied with 10/0 polypropylene suture and lastly, tissues were closed anatomically. The rats were separated into 4 groups. Group 1 rats were control group, the group of rats which 100 mg/kg/day dose of pentoxifylline were given subcutaneously through 7 days as Group 2, the group of rats which 1 mg/kg/day dose of adenosine was given subcutaneously through 7 days as Group 3, and finally, the group of rats which both substances were given through 7 days were determined as Group 4. At the end of 7th day, both carotid arteries (the right side which anastomosis performed on and the left side which anastomosis wasn't performed on) were removed, each in the form of 1 cm segment and had equal distant to anastomosis line. The segments were sent to histopathology laboratory for examination. The biopsies obtained were preserved in formalin solution, stained with hematoxylin-eosin and examined by the same histologist. After all examination, anastomosis progress was evaluated. Evaluation parameters were determined as lumen diameter, lumen area, tunica media area, edema, inflammation, vessel wall injury, intimal hyperplasia, medial atrophy, thrombus, and endothelization. Then, the experiment was terminated by sacrificing the subjects with exsanguinations. Results: Although pentoxifylline and adenosine substances used after vascular interventions separately have inhibitor effects on restenosis, development of neointima and smooth muscle cell proliferation, together use of these two substances created a synergic effect, not an additive effect. Conclusion: Concurrent use of pentoxifylline and adenosine as useful agents for prevention of restenosis, intimal hyperplasia and smooth muscle cell proliferation occurred after vascular interventions can be more effective. Keywords: Pentoxifylline, Adenosine, Restenosis, Intimal hyperplasia, Smooth muscle cell proliferation, Anastomosis, Rat.