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    The Beneficial Effects of Tadalafil on Renal Ischemia-Reperfusion Injury in Rats
    (Karger, 2011) Guzeloglu, Mehmet; Yalcinkaya, Fatih; Atmaca, Soner; Bagriyanik, Alper; Oktar, Suleyman; Yuksel, Oguz; Fansa, Iyad
    Acute renal failure due to ischemia-reperfusion (I/R) injury is a common complication in cardiovascular surgery. We determined the influence of tadalafil on renal injury in a renal I/R model in rats. For this purpose, 21 male Wistar albino rats were separated into 3 groups: sham, placebo and tadalafil. A right nephrectomy was performed, and the left renal pedicles were occluded for 60 min and reperfused for 60 min in the placebo and tadalafil groups. A single dose of tadalafil (10 mg/kg) through an orogastric tube was administered to the tadalafil group. Tubular atrophy with acute inflammation in renal histology, total oxidant status (TOS) and total antioxidant status (TAS) were determined in tissue homogenates. Compared to the tadalafil group, tubular atrophy and acute inflammation was significant in the placebo group. TAS levels were significantly higher in the tadalafil group compared to the placebo (p = 0.01) and sham groups (p = 0.04). While TOS levels were significantly higher in the placebo group (p = 0.03), tadalafil did not significantly alter the TOS levels. The beneficial effects of tadalafil can be attributed to its protective effects on renal tubular cells and inhibition of leukocyte infiltration in renal tissue. We think that tadalafil treatment has an important role in reducing renal injury resulting from renal I/R. Copyright (c) 2010 S. Karger AG, Basel
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    Effect of Tadalafil on Neointimal Hyperplasia in a Rabbit Carotid Artery Anastomosis Model
    (Medical Tribune Inc, 2013) Guzeloglu, Mehmet; Aykut, Koray; Albayrak, Gokhan; Atmaca, Soner; Oktar, Suleyman; Bagriyanik, Alper; Hazan, Eyup
    Purpose: 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. Materials and 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). Conclusion: 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.
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    The effects of zoledronic acid on neointimal hyperplasia: a rabbit carotid anastomosis model
    (Turkish Soc Cardiology, 2011) Guzeloglu, Mehmet; Gul, Mehmet; Reel, Buket; Yurekli, Ismail; Aykut, Koray; Hazan, Eyup
    Objective: The aim of the present study was to investigate the effect of zoledronic acid (ZA), as a matrix metalloproteinase inhibitor, on neointimal hyperplasia in rabbit carotid anastomosis model. Methods: New Zealand male rabbits were divided into two groups as placebo and treatment groups in this experimental study. After anesthesia, the right carotid artery of each rabbit was end-to-end anastomosed with an 8/0 polypropylene suture. Left carotid artery was kept as control without any operation. Placebo group (n=6) received phosphate buffered saline (PBS) (0.5mL/kg/day/s.c.) for 28 days postoperatively, whereas ZA group (n=6) received ZA (100 mu g/kg/day/s.c.) for the same period. After sacrification, the anastomosed and control arteries were isolated. Morphometric and immunohistochemical examinations were performed. Statistical analyses of morphometric and immunohistochemical data were performed using two-way ANOVA and Chi-square test respectively. Results: In PBS group, vascular injury in the anastomosed artery significantly increased the intimal area (anastomosed: 112.51 +/- 61.18 mu m(2)*1000 vs. control: 22.62 +/- 4.26 mu m(2)*1000, p<0.01) and intima/media index (anastomosed: 0.347 +/- 0.29 vs. control: 0.075 +/- 0.01, p<0.05) compared to control artery. ZA significantly reduced the intimal area (39.29 +/- 18.21 mu m(2)*1000, p<0.01) and intima/media index (0.112 +/- 0.07, p<0.05) compared to PBS group. Additionally, a-smooth muscle actin immunopositivity was found significantly decreased in anastomosed arteries from ZA group (ZA: 2.33 +/- 0.52 vs. PBS: 3.50 +/- 0.5, p<0.05). Moreover, intensive gelatinase (MMP-2 and MMP-9) immunoreactivities were clearly seen in anastomosed arteries compared to control arteries from PBS group. ZA apparently decreased immunopositivities for gelatinases in anastomosed arteries. Conclusion: ZA might be a promising agent for prevention of neointimal hyperplasia, which is the most significant cause of graft failures in late postoperative period. (Anadolu Kardiyol Derg 2011; 11: 93-100)