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.

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

Background: 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 µM H2O2 and/or 10 µM 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.

Bedside surgery to treat patent ductus arteriosus in low-birth-weight premature infants.

BACKGROUND: Patent ductus arteriosus (PDA) is commonly seen in premature infants with low birth weights (LBW). It is a condition that has high mortality and morbidity rates. Early closure of the ductus arteriosus may require surgery or medical treatment. However, the decision of first medical approach for symptomatic PDA closure is still debated. In this study, we compared the surgical and medical treatments for the closure of PDA in premature LBW infants. METHODS: This study included 27 premature infants whose birth weights were lower than 1500 g, who were born in the period between 2011 and 2013 and had symptomatic PDA. Patients were separated into two groups: groups A and B. Group A included patients whose PDAs were closed with medical treatment (n = 16), and group B included patients who had undergone surgical operations for PDA closure (n = 11). RESULTS: There were no statistically significant differences between groups A and B when the groups were compared in terms of birth weight, gestational age, respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), sepsis, intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP), and pneumothorax. Although the mortality rate was determined to be lower in group B (2 out of 11, 18.1%) than in group A (7 out of 16, 43.7%), no statistically significant difference was found between the two groups. A statistically significant increase was determined in the incidence of kidney function loss in patient group that received Ibuprofen, a medical treatment, in comparison to the patients who had surgery. CONCLUSION: In conclusion, surgery is a safe method to repair PDA in premature LBW infants. Although there is no remarkable difference between surgery and medical treatment, we suggest that a surgical approach may be used as a first choice to repair PDA considering the lower rate of mortality and morbidity and higher rate of closure compared to medical treatment.

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. METHODS: A total of 27 patients with a history of femoropopliteal bypass operation who was admitted with acute limb ischemia were enrolled in this retrospective study. In cases in which the Fogarty catheter could not be passed through the popliteal anastomosis, the popliteal region was explored and a new bypass or patch plasty was performed for the distal anastomosis. The cases in which the blood circulation was observed in the graft, but in which the Fogarty catheter balloon was stuck in the native vessels on the proximal and distal side of the graft and the balloon could be withdrawn by deflation, were referred to conventional angiography. The stenosis observed in native vessels was managed by endovascular stent grafting and/or balloon dilatation. FINDINGS: Graft patency was achieved in all patients. In 11 patients, conventional angiography was implemented following embolectomy. In these patients, all the occlusions found as significant on angiography were removed by percutaneous transluminal angioplasty. CONCLUSION: Effective use of Fogarty catheter is safe in acute femoropopliteal bypass graft occlusions and in particular, in the planning of further treatment following thrombectomy.

Pulsatile versus non-pulsatile flow to reduce cognitive decline after coronary artery bypass surgery: A randomized prospective clinical trial.

BACKGROUND: In this prospective study, we aimed to compare the effect of pulsatile and non-pulsatile flow on the cognitive functions in patients undergoing coronary artery bypass surgery. METHODS: Patients scheduled for their first coronary artery bypass surgery (n = 148) were randomly assigned to the pulsatile flow group (Group A, n = 75) or non-pulsatil group (Group B, n = 73). Cognitive performance was assessed with (MoCA) montreal cognitive assessment test performed by psychologists before coronary artery bypass surgery and 1 month after the operation. RESULTS: Mild cognitive impairment was seen in 12 (16%) patients and serious cognitive impairment was seen in 1 (1.33%) patient in the pulsatile flow group. In the other group, mild cognitive impairment was detected in 23 (31.50%) patients and serious cognitive decline was found in 3 (4.10%) patients. Mean MoCA scores were 25.86 ± 2.62 in group A and 22.12 ± 2.20 in group B. The difference between two groups was statistically significant (P = 0.041). CONCLUSIONS: We suggest that pulsatile flow has beneficial effects to decrease cognitive dysfunction in patients undergoing on-pump coronary artery bypass surgery.

Investigation of the direct hepatic effects of intramuscular interleukin-8 injection in an experimental rabbit model.

BACKGROUND: The aim of this study was to investigate the effects of intramuscular IL-8 injection on hepatic tissues using an in vivo histopathological animal model. MATERIAL AND METHODS: Twelve New Zealand white rabbits were used for this randomized, controlled, single-blinded interventional study. For 6 days, 1 gluteus maximus muscle was injected daily with 1 mcg/kg of IL-8 in 6 rabbits (Group A). The remaining 6 rabbits (to determine to normal porto-hepatic morphology of the rabbit genus) were in the sham group (Group B). At the end of the 7th day, all rabbits were killed and livers were meticulously harvested. Microscopically, regional tissues were scored according to portal inflammation, focal necrosis, piecemeal necrosis, and total impact. RESULTS: Total impact score, portal inflammation, focal necrosis, and piecemeal necrosis were the histopathologic changes present in a higher incidence in the IL-8 group compared with the control group. The differences were significant when the groups were compared according to total impact score, portal inflammation, focal necrosis, and piecemeal necrosis according to Pearson's correlation (p<0.05). The most significant differences were detected at the total impact scores (p=0.002) and the portal inflammation scores (p=0.008). CONCLUSIONS: Our results showed that IL-8 may damage hepatocytes. This can be the determined target for new therapeutic strategies. Further trials should be designed to obtain definitive results.

Preoperative mild cognitive dysfunction predicts pulmonary complications after coronary artery bypass graft surgery.

OBJECTIVES: In elderly patients with mild cognitive impairment, noncompliance with respiratory exercises, ineffective expectoration, reluctance in mobilization, and difficulty in learning the use of drugs such as inhalers were observed in the early postoperative period after coronary artery bypass graft surgery. It was hypothesized that respiratory complications may be more frequent in these patients, and so the postoperative respiratory complications in patients with preoperative mild cognitive impairment were compared with the postoperative respiratory complications of a control group. DESIGN: A prospective cohort control. SETTING: A university hospital. PARTICIPANTS: Patients undergoing elective coronary artery bypass graft surgery. INTERVENTIONS: Investigators separated 48 patients>70 years old who were scheduled for elective coronary artery bypass graft surgery into two groups: patients with preoperative mild cognitive impairment (group A, n = 25) and patients with no cognitive impairment (control group; group B, n = 23). The patients' cognitive status was evaluated preoperatively by the Montreal Cognitive Assessment test. MEASUREMENTS AND MAIN RESULTS: Pulmonary functions and respiratory complications were evaluated via chest x-rays and spirometry tests preoperatively and postoperatively. A significant difference was observed between the groups, particularly with regard to atelectasis and prolonged ventilation (p<0.001 and p<0.05). No significant impairment was observed in the spirometry tests of the control group. However, a significant deterioration was observed in the postoperative spirometry tests of patients with preoperative mild cognitive impairment. CONCLUSIONS: This study suggested that mild cognitive impairment was associated with pulmonary complications after coronary artery bypass graft surgery.

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. MATERIAL AND METHOD: 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.

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

BACKGROUND: 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 proliferator-activated receptor-γ agonists have antiinflammatory and antioxidant effects. In the present study, we aimed to investigate the effects of pioglitazone, a synthetic peroxisome proliferator-activated receptor-γ 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.

The effects of PPARγ 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. PPARγ agonists inhibit SMC proliferation, migration and lesion formation. In this study, we aimed to investigate the effects of PPARγ agonist rosiglitazone on neointimal hyperplasia and gelatinase (MMP-2 and MMP-9) expressions in rabbit carotid anastomosis model. METHODS: New Zealand white rabbits (n = 13, 2.7-3.2 kg) were divided into placebo and treatment groups. Right carotid artery (CA) was transected and both ends were anastomosed. Treatment group (n = 6) received rosiglitazone (3 mg/kg/day/p.o.) and placebo group (n = 7) received PBS (phosphate buffered saline, 2.5 ml/kg/day/p.o.) for 4 weeks postoperatively. After the sacrification, right and left CAs were isolated. Morphometric analyses and immunohistochemical examinations for gelatinases were performed. RESULTS: Intimal area (0.055 ± 0.005 control vs 0.291 ± 0.020 µm(2) anastomosed, p < 0,05) and index (0.117 ± 0.002 control vs 0.574 ± 0.013 anastomosed, p < 0,01) significantly increased in anastomosed arteries compared to control arteries from placebo group. However, in rosiglitazone-treated group, intimal area (0.291 ± 0.020 PBS vs 0.143 ± 0.027 rosiglitazone, p < 0,05) and index (0.574 ± 0.013 PBS vs 0.263 ± 0.0078 rosiglitazone, p < 0,01) significantly decreased. Furthermore, gelatinase immunopositivity was found to have significantly increased in anastomosed arteries from placebo group and decreased with rosiglitazone treatment. CONCLUSIONS: These results suggest that rosiglitazone may prevent neointimal hyperplasia, which is the most important factor involved in late graft failure, by inhibiting gelatinase enzyme expression.

Intrapericardial teratoma in a newborn: a case report.

We report a successfully surgically intervened case of intrapericardial teratoma, which was diagnosed prenatally. Intrapericardial teratomas are rare cases, and surgical management of those tumors are challenging in this age group. The compression effect of the mass led to misdiagnosis of the anomaly as a transposition of the great vessels. We conclude that intrauterine echocardiography in experienced hands is an essential tool for the follow-up of these patients to detect the pericardial effusion and compression of the cardiac structures, which may cause tamponade and heart failure.

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. Radiologic 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.

Vascular rings: presentation, imaging strategies, treatment, and outcome.

This study aimed to evaluate the presenting symptoms, the effectiveness of imaging methods, and the surgical treatment of vascular rings. Data for 44 patients (32 enrolled prospectively, 12 reviewed retrospectively) over a 10-year period in a tertiary referral center were analyzed. These patients comprised 25 patients with a left aortic arch and an aberrant right subclavian artery, 13 patients with a right aortic arch and a left subclavian artery originating from Kommerell's diverticulum, 1 patient with a right aortic arch and an aberrant left subclavian artery, 3 patients with a double aortic arch, and 2 patients with a pulmonary sling. Respiratory symptoms were found in 25 patients and dysphagia in 6 patients. Atypical symptoms such as reflex apnea, cyanosis, syncope episodes, and exercise-induced wheezing were noted in five patients. Associated congenital heart defects were detected in 41% of the patients. The diagnostic yield was 95.23% for barium esophagography, 54.54% for echocardiography, and 66.66% for computed tomography. The anatomy could be correctly identified by magnetic resonance imaging (MRI) in 97.43% and by angiography in 90.5% of the patients. Of the 30 patients who underwent surgery, 80% were completely relieved of symptoms during a mean follow-up period of 25 ± 33.5 months. Vascular rings should not be overlooked in infants with atypical symptoms. The authors' diagnostic procedure of choice is MRI because it is superior to angiography for delineating the relationship between abnormal vascular structures, trachea, and esophagus.

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

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 µg/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 µm(2)*1000 vs. control: 22.62±4.26 µm(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 µm(2)*1000 , p<0.01) and intima/media index (0.112±0.07, p<0.05) compared to PBS group. Additionally, α-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.

The beneficial effects of tadalafil on renal ischemia-reperfusion injury in rats.

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.

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 2(1/2)year-old child, who sustained mitral valve insufficiency due to isolated rupture of the posterior mitral papillary muscle, which developed after a domestic accident.

Behçet's disease: treatment of popliteal pseudoaneurysm by an endovascular stent graft implantation.

Behçet's disease is a multisystemic chronic autoimmune process that can be responsible for some vascular lesions, in addition to its typical dermatologic lesions. Arterial pseudoaneurysm formation can be diagnosed in this group of patients and generally surgery is indicated. In this report, we discuss an alternative endovascular intervention and its advantages. An endovascular stent graft was placed in the popliteal artery pseudoaneurysm of a 37-year-old male with Behçet's disease. Early results of this procedure are good thus far. Implantation of an endovascular stent graft, an alternative modality in the treatment of pseudoaneurysms, can result in a shorter hospital stay and a significantly shorter period before returning to normal life. General anesthesia and surgical dissection are avoided, thus diminishing morbidity.