Barlas Aytacoglu

N-Acetylcysteine for Preventing Pump-Induced Oxidoinflammatory Response During Cardiopulmonary Bypass

PurposeTo investigate the effect of N-acetylcysteine on preventing pump-induced oxidoinflammatory response during cardiopulmonary bypass (CPB).MethodsForty patients undergoing coronary artery bypass grafting (CABG) were randomly divided into a study group (n = 20), given 50 mg kg−1N-acetylcysteine intravenously for 3 days, and a control group (n = 20) given saline. Serum samples were collected for measurement of myeloperoxidase (MPO), malondialdehyde (MDA), interleukin-6, Α1-acid glycoprotein (AAGP), and C-reactive protein (CRP) during surgery and postoperatively.ResultsThe MPO and MDA values showed a similar pattern during and after CPB in the study group, with significantly less variance than in the control group. Interleukin-6 showed similar patterns in the two groups, but the data from 30 min after the start of CPB and from 6 h post-CPB were significantly different. The AAGP and CRP values were both elevated during CPB in the two groups without a significant difference, but 6 and 24 h post-CPB, the values were significantly higher in the control group than in the study group.ConclusionsN-Acetylcysteine decreased pump-induced oxidoinflammatory response during CPB, suggesting that it could be a novel therapy for assisting in the prevention of CBP-induced oxidoinflammatory damage.

Decreased Serum Total Antioxidant Status and Erythrocyte-Reduced Glutathione Levels Are Associated with Increased Serum Malondialdehyde in Atherosclerotic Patients

BACKGROUND Coronary artery disease is the significant cause of morbidity and mortality today. The treatment of coronary artery disease is improving, but its prevalence is increasing. Both primary and secondary prevention measures are of vital importance. METHODS In this study, vitamin C, total antioxidant status, malondialdehyde in serum and erythrocyte-reduced glutathione levels were investigated in patients with atherosclerosis and compared with those of controls. Levels of serum MDA, vitamin C, total antioxidant status, and erythrocyte-reduced glutathione were determined according to the methods of Yagi, Bauer et al., Miller et al., and Beutler, respectively. RESULTS Erythrocyte-reduced glutathione, serum vitamin C, total antioxidant status, and malondialdehyde values of both patients with atherosclerosis and controls were as follows: 2.80 +/- 0.76, 5.82 +/- 0.67 micromol GSH/g Hb; 1.00 +/- 0.19, 1.62 +/- 0.30 mg/dL; 0.86 +/- 0.14, 1.43 +/- 0.16 mmol/L, and 4.26 +/- 0.9, 1.02 +/- 0.80 nmol/mL, respectively. There was a decrease in the levels of serum vitamin C, erythrocyte-reduced glutathione, and total antioxidant status (p <0.001), and increase in the levels of serum malondialdehyde (p <0.001) in patients with atherosclerosis when compared with those of controls. CONCLUSIONS Because treatment of atherosclerosis is improving, our results suggest that antioxidant agents may have preventive roles in the formation of atherosclerosis.

3-Nitrotyrosine in atherosclerotic blood vessels

Abstract The effect of peroxynitrite on the development of atherosclerosis is one of the major foci of recent studies. Here, the cytotoxic effect of peroxynitrite was investigated by quantitatively measuring nitrated tyrosine, 3-nitrotyrosine (3-NT) levels in atherosclerotic blood vessels. Atherosclerotic vessels were obtained from the patients who underwent either coronary artery or peripheric artery bypass surgery. Internal thoracic arteries of the patients were treated as non-atherosclerotic control vessels. 3-NT was measured by reverse-phase HPLC and plasma nitrite-nitrate levels were measured by spectrophotometry. 3-NT levels were significantly elevated in atherosclerotic vessels (46.6±23.3 nmol/mg protein, n = 15; p < 0.001) in comparison to control vessels (15.8±2.5 nmol/mg protein, n = 10). Vessel 3-NT correlated weakly with plasma nitrate levels (r = 0.38). Thus, atherosclerotic arteries have higher 3-NT levels than non-atherosclerotic blood vessels.

Alcohol-induced lung damage and increased oxidative stress.

Background: Alcohol-induced lung damage may be associated with increased oxidative stress. Objective: Our aim was to investigate alcohol-induced changes in the biochemistry and histopathology of the lung. Methods: Rats were divided into two groups, a control group and an ethanol group. The ethanol group received 2 g/kg ethanol (total: 3 ml) intraperitoneally. The controls were given the same amount of saline via the same route. Three hours later, the rats were sacrificed, and blood and lung tissue samples were obtained. Oxidative stress was assessed by measuring the levels of erythrocyte reduced glutathione (GSH), tissue malondialdehyde (MDA), myeloperoxidase (MPO) and Na+-K+ ATPase. Histopathologic evaluation of the lung tissues was also performed. Results: In the ethanol group, serum and tissue MDA levels and MPO activities were increased (p = 0.007, p = 0.001 and p = 0.000), and lung tissue Na+-K+ ATPase activities and erythrocyte GSH were decreased (p = 0.001 and p = 0.000) compared to the controls. Histopathologic examination demonstrated alveolocapillary thickening, alveolar degeneration, leukocyte infiltration and erythrocyte extravasation in the lungs of the ethanol group (p < 0.05). Conclusion: These results suggest that high-doseacute alcohol administration aggravates systemic and local oxidative stress leading to acute lung injury, ranging from mild pulmonary dysfunction to severe lung injury. It should be borne in mind that rapid onset of the acute respiratory distress syndrome (ARDS) may also be due to increased oxidative stress following alcohol abuse, especially when ischemic disturbances, e.g. coronary heart disease, acute ischemia of the extremities and traumatic accidents, are concomitantly present. Therefore, precautions against ARDS may prevent morbidity and mortality in alcohol-induced lung damage in at-risk patients.

Effects of trimetazidine on tissue damage in kidney after hindlimb ischemia-reperfusion.

The objective of this study was to investigate the effects of trimetazidine (TMZ) on tissue damage in kidney after hindlimb ischemia-reperfusion (I/R), by assessing blood biochemical assay and histopathological analysis. Adult male Wistar rats were divided into two groups. TMZ 10 mg kg(-1)day(-1) was administrated twice a day for 10 days to the treatment group (group T, n=10). Sham group was given only 5% gum arabic (group S, n=10). On 11th day of treatment, 8h I/R period was performed on right hindlimb of the rats. At the end of reperfusion period, a 5 ml blood withdrawn from ascending aorta for biochemical assays and their right kidneys were harvested for histopathological examination. Superoxide dismutase, Na(+)-K(+) ATPase, and reduced glutathione levels were significantly increased in group T (P<0.001). On the other hand, myeloperoxidase and malondialdehyde levels were significantly less in group T than group S (P<0.001). Kidneys from the sham-operated group displayed intense leukocytic infiltration in histopathological examination. These overall results strongly suggested that TMZ contributes renal protection from hindlimb I/R injury by decreasing systemic oxidative stress.

Pressure applied during surgery alters the biomechanical properties of human saphenous vein graft

Pressure applied during harvesting of the saphenous vein (SV) graft in coronary artery bypass surgery might change its mechanical properties and thereby decrease the patency. This study was performed to assess the mechanical properties of the SV graft distended manually with different levels of pressure and to determine the pressure level that induces changes in its structure and mechanics. Saphenous vein graft segments, collected from 36 patients undergoing coronary artery bypass surgery, were distended with pressures of either 50–60, 75–100, or 130–150 mmHg. Grafts were tested for the stress–strain relationship; the Young’s moduli at the low- and high-strain regions were calculated, and their structures were examined by light and electron microscopy. Pressures of 50–60 mmHg did not influence the mechanics of the vein graft, whereas pressures of 75–100 mmHg elevated the elastic modulus of the vein at the low-strain region while pressures above 130 mmHg increased the elastic moduli at both low- and high-strain regions. There was a prominent loss of microfibrils at all distending pressure levels. The mechanical results suggest that distending pressures above 75 mmHg might play a role in graft failure. Furthermore, the absence of microfibrils surrounding elastin suggests that application of distending pressures, even as low as 50 mmHg, can cause degeneration of the elastic fibers following implantation, increasing the stiffness of the graft and thus impairing the graft’s function under its new hemodynamic conditions.

Affirmative Effects of Iloprost on Apoptosis during Ischemia-Reperfusion Injury in Kidney as a Distant Organ

Abstract Objective: Apoptosis and its regulatory mechanisms take part in renal ischemia–reperfusion (I/R) injury which can result in acute renal failure and the inhibition of the caspase is considered as a new therapeutic strategy. In this context, we investigated the antiapoptotic and cytoprotective effects of iloprost, a prostacyclin analog, in kidney as a distant organ. Methods: Wistar albino rats were randomized into five groups (n = 12 in each) as sham, ischemia, I/R, iloprost (10 μg kg−1), and I/R + iloprost (10 μg kg−1). A 4 h reperfusion procedure was carried out after 4 h of ischemia. Caspase-8 was evaluated for death receptor-induced pathways, whereas caspase-9 was evaluated for mitochondria-dependent pathways and caspase-3 was investigated for overall apoptosis. Superoxide dismutase (SOD) enzyme activity and nitrite content as an indicator of nitric oxide (NO) production were also analyzed in kidney tissues. Results: Caspases-3, -8, and -9 were all significantly elevated in both ischemia and I/R groups compared to the sham group; however, treatment with iloprost reduced caspases-3, -8, and -9. SOD enzyme activity was attenuated by iloprost when compared to ischemic rats. The different effects of NO were found which change according to the present situation in ischemia, I/R, and treatment with iloprost. Conclusions: These findings suggested that iloprost prevents apoptosis in both receptor-induced and mitochondria-dependent pathways in renal I/R injury and it may be considered as a cytoprotective agent for apoptosis. Understanding the efficiency of iloprost on the pathways for cell death may lead to an opportunity in the therapeutic approach for renal I/R injury.

Comparison and evaluation of experimental mediastinitis models: precolonized foreign body implants and bacterial suspension inoculation seems promising

BackgroundPost-sternotomy mediastinitis (PSM) is a devastating surgical complication affecting 1–3% of patients that undergo cardiac surgery. Staphylococcus aureus is one of the most commonly encountered bacterial pathogen cultured from mediastinal samples obtained from patients with PSM. A component of the membrane of the gram positive bacteria, lipoteichoic acid, stimulates the blood monocytes and macrophages to secrete cytokines, radicals and nitrogen species leading to oxido-inflammatory damage. This seems to be responsible for the high mortality rate in PSM. For the evaluation of the pathogenesis of infection or for the investigation of alternative treatment models in infection, no standard model of mediastinitis seems to be available. In this study, we evaluated four mediastinitis models in rats.MethodsThe rats were divided into four groups to form different infection models. Group A: A suspension of 1 × 107 colony-forming units Staphylococcus aureus in 0,5 mL was inoculated from the right second intercostal space into the mediastinum. Group B: A hole was created in the right second intercostal space and a piece of stainless-steel implant with a length of 0.5 cm was inserted into the mediastinum and a suspension of 1 × 107 cfu bacteria in 0,5 mL was administered via the tail vein. Group C: Precolonized stainless-steel implant was inserted into the mediastinum. Group D: Precolonized stainless-steel implant was inserted into the mediastinum and the bacteria suspension was also injected into the mediastinum. On the 10th day, rats were sacrificed and the extension of infection in the mediastenae was evaluated by quantitative cultures. Myeloperoxidase activity (MPO) and malondialdehyde (MDA) levels were determined in the sera to evaluate the neutrophil activation and assess the inflammatory oxidation.ResultsThe degree of infection in group C and D were 83.3% and 100% respectively (P < 0.001). MDA levels were significantly higher in these two groups than the others (P < 0.001).ConclusionInfected implants and high bacterial concentration administration were the two important components that played a significant role in the outcome of a successful infection in mediastinum in a rat model.

Role of ACE I/D gene polymorphisms on the effect of ramipril in inflammatory response and myocardial injury in patients undergoing coronary artery bypass grafts.

BackgroundAngiotensin-converting enzyme (ACE) inhibitors block angiotensin II formation and release bradykinin, which is effective in the regulation of oxidoinflammatory injury. Some reports denote alterations in the effectiveness of ACE inhibitors in association with ACE insertion/deletion (I/D) gene polymorphisms. This study investigates the effects of ramipril on the oxidoinflammatory cytokines (IL-6, IL-8, TNF-alpha) and TnT (myocardial injury marker) and their alteration in association with ACE I/D gene polymorphisms.MethodsThe study group (n = 51) patients received ramipril before coronary artery bypass grafting (CABG), while patients not receiving ramipril (n = 51) constituted the controls. TNFα, IL-6, and IL-8 were evaluated using ELISA and TnT by electrochemiluminescence methods before the induction of anesthesia (t1), at the 20th minute following cross-clamping (t2), at the end of the operation (t3), and at the 24th hour from the commencement of anesthesia (t4). Genotyping was performed by PCR.ResultsDifferences between the groups were significant at t4 for the TNFα and at t3 for IL-6 (p < 0.05). The TnT levels increased from t2 onward in the control group and were highest in t3. Changes in t3 and t4 values in both groups according to their t1 values were significant (p < 0.05). However, differences between the groups were insignificant (p > 0.05). The IL-6, IL-8, TNFα, and TnT serum levels had no correlation with the ACE I/D gene polymorphism.ConclusionLow cytokine and TnT levels in the study group, especially after cross-clamping, may indicate the protective effect of ramipril from oxidoinflammatory injury. This effect did not appear to be associated with the ACE I/D gene polymorphism.

Impact of invasive strategy for the management of patients with cardiogenic shock after acute myocardial infarction

ObjectiveThis study evaluates the influence of early revascularization (with percutaneous transluminal coronary angioplasty (PTCA) and coronary surgery) on short- and long-term survival in patients with cardiogenic shock complicating acute myocardial infarction (AMI). Methods and resultsIn-hospital and 6-month survival were retrospectively determined on day 193 (65–270, median ±25th and 75th percentiles) in 87 patients who either underwent early invasive reperfusion (group A, n=60) or those who were treated conservatively (group B, n=27). In-hospital mortality was 37% in group A and 56% in group B (P=0.192). Six-month mortality was statistically lower in group A than in group B (30 patients (50%) compared with 25 patients (93%), P=0.005). Being a woman and older age were found to be factors increasing mortality. Lower mortality in the long term was strongly associated with revascularization (odds ratio=0.08, 95% confidence interval=1.54–109). PTCA was found to be an independent predictor of long-term survival (odds ratio= 0.22, 95% confidence interval=0.049–1.00, P=0.050), by multiple logistic regression. ConclusionsIn conclusion, this study suggests that early revascularization improves long-term survival of patients with cardiogenic shock complicating AMI, even after adjustment for baseline differences between patients who underwent early revascularization and those who did not.