The effects of zoledronic acid on neointimal hyperplasia: a rabbit carotid anastomosis model

WOS: 000288827900002PubMed ID: 21285021Objective: 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

Advanced treatment of acute femoropopliteal bypass graft occlusion with Fogarty catheter guidance

Purpose: The guiding role of the Fogarty catheter was investigated among patients suffering from limb ischemia due to acute femoropopliteal bypass graft occlusion

The effects of PPAR gamma agonist rosiglitazone on neointimal hyperplasia in rabbit carotid anastomosis model

Background: Neointimal hyperplasia involving smooth muscle cell (SMC) proliferation, migration and extracellular matrix (ECM) degradation is an important component of atherosclerosis. It develops as a response to vascular injury after balloon angioplasty and vascular graft placement. Matrix metalloproteinases (MMPs) induce SMC proliferation, migration and contribute to intimal hyperplasia by degrading ECM. PPAR. agonists inhibit SMC proliferation, migration and lesion formation. In this study, we aimed to investigate the effects of PPAR. agonist rosiglitazone on neointimal hyperplasia and gelatinase (MMP-2 and MMP-9) expressions in rabbit carotid anastomosis model

Repair of Isolated Mitral Papillary Muscle Rupture Consequent to Blunt Trauma in a Small Child

Blunt thoracoabdominal trauma is most often caused by high-velocity motor-vehicle accidents or by falls from a height. The clinical spectrum of cardiac injuries arising from this type of trauma varies from myocardial contusion to valvular rupture. Intracardiac valvular rupture is rarely observed, and few cases have been reported. The youngest of the patients in cases reported to date was 6 years of age. Here we report the case of a 2½year-old child, who sustained mitral valve insufficiency due to isolated rupture of the posterior mitral papillary muscle, which developed after a domestic accident

Low-dose doxycycline inhibits hydrogen peroxide-induced oxidative stress, MMP-2 up-regulation and contractile dysfunction in human saphenous vein grafts

WOS: 000469125200001PubMed ID: 31213768Background: Cardiopulmonary bypass (CPB) applied during coronary artery bypass grafting (CABG), promotes inflammation, generation of reactive oxygen species (ROS) and up-regulation of matrix metalloproteinases (MMPs). All these complications may lead to contractile dysfunction, restenosis and early graft failure, restricting long-term efficacy of bypass grafts. Low-dose doxycycline is a potent MMP inhibitor and ROS scavenger. In this study, we aimed to investigate the effects of doxycycline on ROS generation, MMP regulation and contractile dysfunction induced by H2O2 in human saphenous vein (HSV) grafts. Methods: HSV grafts (n=7) were divided into four groups after removing endothelial layer by mechanical scratching and incubated with 10 mu M H2O2 and/or 10 mu M doxycycline for 16 hrs. Untreated segments served as control. Concentration-response curves to noradrenaline (NA), potassium chloride (KCl), serotonin (5-HT) and papaverine were performed. Superoxide anion and other ROS levels were determined by using lucigenin- and luminol-enhanced chemiluminescence assays, respectively. Expression/activity of gelatinases (MMP-2/MMP-9) was examined by gelatin zymography. MMP-13 expression was evaluated by immunostaining/immunoscoring. Results: H2O2 incubation increased superoxide anion and other ROS levels. Doxycycline prevented these increments. H2O2 suppressed contractile responses to NA, KCl and 5-HT. Doxycycline ameliorated contractions to NA and KCl but not to 5-HT. H2O2 or doxycycline did not altered relaxation to papaverine. MMP-2 and MMP-13 expression increased with H2O2, but doxycycline inhibited MMP-2 up-regulation/activation. Conclusion: Low-dose doxycycline may have beneficial effects on increased oxidative stress, MMP up-regulation/activation and contractile dysfunction in HSV grafts.Scientific Research Foundation of Ege UniversityEge UniversityThe authors would like to thank to Prof. Bekir Ugur Ergur for contributions to immunohistochemical analyses, to Hatice Uluer for valuable statistical consultancy and to Scientific Research Foundation of Ege University for the financial support

The effects of PPAR-gamma agonist pioglitazone on renal ischemia/reperfusion injury in rats

WOS: 000318616500033PubMed ID: 22981741Background: Acute renal failure due to renal ischemia/reperfusion (IR) injury is a significant clinical problem in cardiovascular surgery. Reactive oxygen species and inflammation play essential roles in the pathophysiology of IR injury. Matrix metalloproteinases (MMPs) are enzymes that play important roles in inflammation and mediate extracellular matrix degradation. It is known that peroxisome proliferatoreactivated receptor-gamma agonists have antiinflammatory and antioxidant effects. In the present study, we aimed to investigate the effects of pioglitazone, a synthetic peroxisome proliferatoreactivated receptor-gamma agonist, on MMPs and oxidative stress in a renal IR injury model in rats. Materials and methods: Male Wistar albino rats were divided into three groups: control (n = 7), placebo (n = 7; saline/p.o.), and pioglitazone (n = 7; 5 mg/kg/day/p.o.). In the control group, a right nephrectomy was conducted without left renal IR injury. In the placebo and pioglitazone groups, pretreatments were started 3 d before operation. In both groups, left renal pedicles were clamped for 60 min and then reperfused for 60 min. Paraffinized renal sections were evaluated histopathologically. Furthermore, expressions of MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2, superoxide dismutase 1 (SOD1), and p47-phox/p67-phox subunits of NADPH oxidase were determined by immunostaining and scoring. Results: In the placebo group, renal IR injury induced diffuse tubular necrosis and intense acute inflammation, but pioglitazone inhibited these effects. MMP-2, MMP-9, and TIMP-2 expression increased in the placebo group. However, while MMP-2 and -9 expression decreased, TIMP-2 expression did not change in the pioglitazone group. p47-phox/p67-phox expression increased in the placebo group, but SOD1 expression did not change. Pioglitazone diminished p47-phox/p67-phox expression, whereas it enhanced SOD1 expression. Conclusion: Our results suggest that pioglitazone might be helpful to reduce renal IR injury because of its antiinflammatory and antioxidant effects. (C) 2013 Elsevier Inc. All rights reserved

Pioglitazone inhibits oxidative stress, MMP-mediated inflammation and vascular dysfunction in high glucose-induced human saphenous vein grafts

Aims: The aim of this study was to investigate the effects of pioglitazone on reactive oxygen species (ROS), expressions/activities of MMPs and TIMP-2, and VSMC proliferation and vascular reactivity in high glucose (HG)-induced human saphenous vein (HSV) grafts. Methods: HSV grafts (n = 10) obtained from patients undergoing CABG were incubated with 30 mM glucose and/or 10 μM pioglitazone or 0.1 % DMSO for 24 h after endothelium removal. ROS levels were examined by chemiluminescence assay, MMP-2,-9,-14, TIMP-2, and α-SMA expression/activity was determined by gelatine zymography/immunohistochemistry. Vascular reactivity to potassium chloride, noradrenaline, serotonin, prostaglandin F2α and papaverine was assessed in HSVs. Results: HG induced superoxide anion (SA) (123 %) and other ROS levels (159 %), up-regulated MMP-2 expression (180 %)/activity (79 %), MMP-14 expression (24 %) and MMP-9 activity while down-regulating TIMP-2 expression (27 %). HG elevated total MMP-2/TIMP-2 ratio (483 %) and MMP-14/TIMP-2 ratio (78 %). However, HG plus pioglitazone inhibited SA (30 %) and other ROS levels (29 %), down-regulated MMP-2 expression (76 %)/activity (83 %), MMP-14 expression (38 %) and MMP-9 activity, while reversing TIMP-2 expression (44 %). HG plus pioglitazone decreased total MMP-2/TIMP-2 ratio (91 %) and MMP-14/TIMP-2 ratio (59 %). HG impaired contractions to all agents but pioglitazone improved them. Conclusions: Pioglitazone may contribute to the prevention of restenosis and maintaining vascular function in HSV grafts of DM patients undergoing CABG

A Congenital Arteriovenous Malformation Originating from the Aorta Locating in the Posterior Mediastinum

Vascular malformations located in the posterior mediastinum are extremely rare. Most of them are found coincidentally during routine examinations. Only a small percentage of these posterior mediastinal arteriovenous malformation cases may cause symptoms such as dyspnea due to compression of surrounding tissues. Radio logic imaging can be insufficient in some cases for differential diagnosis. Because of their vascular nature, diagnostic needle biopsy may have a high risk of bleeding. Open surgical resection is a safe treatment choice under many circumstances, and it helps the diagnosis as well. In this paper, a case of a 31-year-old male is presented with an incidentally diagnosed arteriovenous malformation, originating from the descending aorta and located in the posterior mediastinum

Effect of Tadalafil on Neointimal Hyperplasia in a Rabbit Carotid Artery Anastomosis Model

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