Akın Serdar

Effect of N-acetylcysteine on oxidative stress and ventricular function in patients with myocardial infarction.

Recent evidence suggests that postischemic myocardial dysfunction (“stunning”) may be mediated by oxygen free radicals. Various studies have reported the beneficial effects of antioxidants in ischemia–reperfusion injury. The aim of this study was to assess the effect of N-acetylcysteine (NAC) treatment on oxidative stress, infarct size, and left ventricular (LV) function, as adjunct therapy in myocardial infarction (MI). Patients with acute MI received either 15 g NAC infused over 24 h (n = 15) or no NAC (n = 15), combined with streptokinase. Peripheral venous blood was serially sampled to measure creatine kinase (CK)-MB levels. Plasma malondialdehyde (MDA) level was measured at admission and after 4 and 24 h. Echocardiography was performed within 3 days of MI and after 3 months. At admission, plasma MDA levels were not different between the groups. In the NAC-treated patients plasma MDA levels decreased, whereas in the nontreated NAC patients MDA levels increased at 4 and 24 h (P < 0.01 and P < 0.001, respectively). Left ventricular ejection fraction was higher (P < 0.05) and LV end-systolic and end-diastolic diameters were lower (P < 0.001 and P < 0.001) in patients receiving NAC on day 3. Left ventricular wall motion score index was significantly lower in patients treated with NAC on day 3 (P < 0.05). Left ventricular diastolic parameters were not different whether patients were treated with NAC or not. No difference in reduction of infarct size was detected between the groups according to CK-MB levels. It was thus demonstrated that administration of NAC in combination with streptokinase significantly diminished oxidative stress and improved LV function in patients with acute MI. These encouraging results would justify the performance of a larger controlled study.

The effect of orlistat-induced weight loss on interleukin-6 and C-reactive protein levels in obese subjects.

Objective — Inflammation plays a major role in the pathogenesis of atherosclerosis. Obesity is an independent risk factor for cardiovascular disease, which may be mediated by increased secretion of proinflammatory cytokines by adipose tissue. The aim of this study is to investigate changes in the inflammatory markers interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) during weight reduction with orlistat treatment in obese patients. Methods and results — Thirty-six obese (BMI: 36.1 ± 3.4 kg/m2) and 11 non-obese (BMI: 22.9 ± 1.7 kg/m2) subjects were studied. IL-6 and hs-CRP levels were evaluated at baseline. In obese subjects after treatment of orlistat 120 mg three times daily for 6 months, IL-6 and hs-CRP levels were repeated. Levels of circulating IL-6 (p < 0.05) and hs-CRP (p < 0.01) were significantly higher in the obese group than in the non-obese group. Plasma IL-6 (r = 0.29 and p < 0.05) and CRP (r = 0.35 and p < 0.05) concentrations correlated positively with the level of obesity assessed by BMI at baseline. After 6 months of orlistat treatment in obese subjects, the mean weight of the patients decreased by 6.8 kg, the BMI by 3.2 kg/m2. Compared with baseline, weight loss was associated with significant reductions of IL-6 (p < 0.001) and hs-CRP (p < 0.001) levels. Conclusion — In summary plasma IL-6 and hs-CRP levels were increased in obese patients. Orlistatinduced weight reduction was associated with decreasing levels of both IL-6 and hs-CRP in obese subjects. Because inflammatory mediators may be directly involved in atherogenesis, this would suggest that interventions to reduce IL-6 and CRP levels could be cardioprotective.

The relation between oxidant and antioxidant parameters and severity of acute coronary syndromes.

Objective — Acute coronary syndromes (ACS) encompass a continuum of cardiac ischaemic events, ranging from unstable angina pectoris (UA) to ST-segment elevation myocardial infarction (STEMI). Oxidative stress may play an important role in the pathogenesis of acute coronary diseases. In the present study, we examined the associations between lipid and protein susceptibility to oxidation and total sialic acid (SA) and antioxidant status and the severity of ACS as determined by having UA, non-STEMI or STEMI. Methods and results — The study sample consisted of 102 patients with ACS and 45 controls. Malondialdehyde (MDA) as a marker of lipid peroxidation and protein carbonyls as a marker of protein oxidation were measured to show the susceptibility to oxidation.Antioxidant status was determined by measuring the carotenoids, vitamin C and vitamin E levels and paraoxonase and arylesterase activities. In addition to conventional lipid and lipoprotein analysis, MDA and vitamin E were quantitated by high-performance liquid chromatography.Total SA and other oxidant and antioxidant parameters were studied spectrophotometrically.As expected, patients had significantly higher total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, lipoprotein (a), apolipoprotein (apo) B values and lower high-density lipoprotein cholesterol and apoAI values than controls. Our results demonstrated significant increases both in total SA levels and in indicators of oxidative stress in patients with ACS compared with the controls. However, antioxidant parameters were decreased in patients with ACS. When the patients were divided into groups with UA, non-STEMI and STEMI, respectively, total SA and oxidant parameters were significantly increased and antioxidant parameters were significantly decreased in going from UA to STEMI. Conclusions — Our study shows gradually increased lipid and protein oxidation and total SA and gradually decreased antioxidant status when the conditions advance from UA to STEMI.These results indicate that these markers may be useful both in understanding plaque destabilization and in determination of risk stratification of patients. Also, measurement of these markers may provide a noninvasive window to study atherosclerotic lesions.

Effect of successful coronary angioplasty and stent implantation on QT dispersion.

BACKGROUND QT dispersion (defined as maximal QT interval minus minimal QT interval), as assessed using the surface ECG, has been shown to reflect regional inhomogeneities in ventricular repolarization. The aim of this study was to show the effect of coronary revascularization, by successful coronary angioplasty or stent implantation, on QT dispersion. METHODS QT dispersion was defined on each ECG as the difference between the maximal and minimal measurements of QT interval. Of 135 patients studied, 52 patients underwent coronary angioplasty and 84 patients underwent stent implantation. Maximum and minimal QT interval and QT dispersion were measured using 12-lead electrocardiography before and 24 h after each successful procedure. RESULTS QT dispersion decreased from 51 +/- 12 ms at baseline to 37 +/- 10 ms 24 after the procedure (P < 0.001). Before the procedure, the QT dispersion of patients undergoing angioplasty and stent implantation was 50 +/- 13 and 52 +/- 10 ms, respectively. After the procedure, the QT dispersions were 34 +/- 9 and 38 +/- 10 ms, respectively (P < 0.001). QT dispersion was significantly lower in both groups after the procedure. No differences were observed between the QT dispersions of patients undergoing angioplasty and of those undergoing stent implantation. CONCLUSIONS Successful coronary angioplasty and stent implantation significantly reduced QT dispersion. The decreased QT dispersion may have been caused by improvements in myocardial perfusion and may be beneficial in reducing the likelihood of arrhythmias occurring.

The relationship of serum ferritin with malondialdehyde concentration in patients with coronary artery disease: Ferritin and oxidative stress in CAD

It has been suggested that the risk of coronary heart disease increased with increasing body iron stores. Free iron catalyzes the generation of free radicals and free radicals promote the oxidation of lipids. The aim of this study was to determine the association of serum ferritin levels with coronary artery disease (CAD) and to establish the relation of ferritin to the lipid peroxidation product malondialdehyde (MDA). The study included 188 patients. Thirty-eight patients (mean age: 55±9 years) had angiographically normal coronary arteries and 150 patients (mean age: 54±10 years) had significant stenosis at least in one coronary artery. Serum ferritin, total iron binding capacity (TIBC), MDA levels, lipoprotein variables and CAD risk factors were determined in all patients. Serum ferritin levels were significantly higher in patients with CAD compared with control groups (105±65 ng/ml versus 83±71 ng/ml) (p<0.01). TIBC was lower in patients with CAD (333±62 µg/dl) versus 348±48 µg/dl), (p<0.05). In patients with CAD, serum MDA levels were significantly higher when compared with control groups (8.1±2 nmol/ml versus 5.9±1.8 nmol/ml), (p<0.001). There were positive correlation between ferritin and MDA levels (r=0.20, p=0.02) and negative correlation between TIBC and MDA levels (r=0.22, p=0.001). These findings support the concept that iron, being an important transition metal, might contribute to atherogenesis, along with the classic risk factors. The results are also in agreement with the concept that iron overload would elevate the risk of CAD by promoting the lipid peroxidation.

Relation between lipoprotein (a) and in vitro oxidation of apolipoprotein B-containing lipoproteins.

OBJECTIVES To assess the relationship between lipoprotein (a) [Lp (a)] and lipoprotein oxidation in patients with coronary artery disease (CAD). DESIGN AND METHODS Oxidation of apolipoprotein (apo)B-containing lipoproteins, vitamin E, carotenoids, lipid-lipoprotein levels were determined in 171 CAD and 70 non-CAD subjects. RESULTS In CAD patients with Lp (a) concentrations >/= 30 mg/dL; total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA), and apo B levels were significantly higher and lag-time and age were significantly lower than those of CAD patients with Lp (a) concentrations < 30 mg/dL. In non-CAD subjects with Lp (a) concentrations >/= 30 mg/dL; TC, LDL-C, and vitamin E levels were significantly higher and lag-time was significantly lower than those of non-CAD subjects with Lp (a) concentrations < 30 mg/dL. In CAD patients, Lp (a) correlated negatively with lag-time and positively with MDA levels. Lp (a) correlated negatively with lag-time and vitamin E levels in non-CAD subjects. CONCLUSIONS We have shown that plasma apo B-containing lipoproteins of both CAD and non-CAD subjects with Lp (a) levels >/= 30 mg/dL are more susceptible to in vitro oxidative modification than those of subjects with Lp (a) levels < 30 mg/dL. The relationship between Lp (a) and enhanced susceptibility of apo B-containing lipoproteins to oxidation, appears to support routine investigation of Lp (a).