Ozlem Karakurt

Erythropoietin reduces lipopolysaccharide-induced cell Damage and midkine secretion in U937 human histiocytic lymphoma cells

IntroductionErythropoietin (EPO) is a haematopoietic stimulatory protein that is used to treat anaemia in patients on dialysis. In addition, EPO has been shown to have anti-inflammatory properties, which may be important as dialysis patients tend to exist within a chronic, low-grade inflammatory state, and tend to be more susceptible to infections. It has been suggested that EPO has direct immunomodulatory potency on monocytes/macrophages.MethodsIn this study, we aimed to clarify the effects of EPO during the inflammatory processes in human mononuclear phagocytic cells by monitoring the secretion of the following cytokines; midkine, tumour necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). For this purpose, U937 human histiocytic lymphoma cell lines were used. Time-dependent effects of varying doses of EPO (0.1 to 50 IU/ml) treatment during lipopolysaccharide (LPS)-mediated cytotoxicity was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide test. LPS-stimulated midkine secretion was measured immunohistochemically and quantification of TNF-α, IL-6 and midkine secretion was achieved by ELISA.ResultsEPO treatment prevented the direct toxic effects of LPS on the U937 cells. TNF-α, IL-6 and midkine secretions were found to increase in the U937 cells in response to LPS treatment. Interleukin-6 response was varied in a doseand time-dependent manner.ConclusionTreatment with EPO significantly inhibits the LPS-induced secretion of midkine and TNF-α regardless of the dosage. The data presented here provide the first evidence to indicate that EPO treatment directly reverses some of the cytotoxic and secretory effects of LPS in mononuclear cells. Inhibition of midkine secretion might be responsible for the anti-inflammatory role of EPO.

P-Wave dispersion increases in prehypertension

Background. Prolongation of P‐wave durations and increased P‐wave dispersion are independent predictors of atrial fibrillation (AF). AF is the most common arrhythmia of the general population. Prehypertension, including those with systolic blood pressure ranging from 120–139 mmHg or diastolic blood pressure ranging from 80–89 mmHg was described by JNC7. Prehypertension is the predictor of development of hypertension in the future. Prehypertension is associated with excess cardiovascular morbidity and mortality. In this study, we evaluated relationship between prehypertension and P‐wave dispersion. Methods. Seventy‐eight prehypertensive patients (group 1: mean age 44.6±11.2 years; 45 male) and 78 normotensive patients (group 2: mean age 43.3±7.0 years; 43 male) were enrolled in this study. Standard 12‐lead ECGs were recorded in all patients using a paper speed of 50 mm/s. In all patients, transthoracic echocardiographic examination was performed. Results. Pmax and P‐wave dispersion were significantly higher in group 1 compared with group 2 (103.59±19.8 ms vs 93.59±13.4 ms, p<0.001; 50.51±18.6 ms vs 39.85±10.6 ms, p<0.001, respectively). Conclusion. Pmax and P‐wave dispersion increase in prehypertensive patients compared with normotensive patients. This data might show increased risk of AF in prehypertension.

Association between plasma asymmetrical dimethylarginine activity and severity of aortic valve stenosis

Objectives Aortic valve stenosis is the most common valvular heart disease in the Western world. The most common cause of aortic valve stenosis in adults is calcification of a normal trileaflet or congenital bicuspid valve. Calcific aortic valve stenosis is an active disease process characterized by mechanical stress, endothelial damage, lipid accumulation, inflammation, synthesis of extracellular matrix proteins, and calcification, reminiscent of atherosclerosis in many aspects. Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase which reduces the bioavailability of nitric oxide and begets endothelial dysfunction. The goal of this study was to examine the association between ADMA activity and severity of aortic valve stenosis. Methods One hundred and nine patients were included in this study. Patients were grouped as those with mild aortic stenosis (42 patients, group 1), moderate aortic stenosis (36 patients, group 2), and severe aortic stenosis (31 patients, group 3). ADMA activity was measured by ELISA kit. Results Mean ADMA activity in group 3 was significantly higher than that in groups 1 and 2 (1.94 ± 0.45 vs. 0.87 ± 0.37 μmol/l, P < 0.001 and 1.94 ± 0.45 vs. 1.34 ± 0.52 μmol/l, P < 0.001, respectively). Serum ADMA activity was positively correlated with mean aortic gradient and maximum aortic gradient and negatively correlated with aortic valve area. Conclusion Our results showed that serum ADMA activity is higher in patients with severe aortic valve stenosis. ADMA activity is positively correlated with aortic valve stenosis severity. Serum ADMA level may be used as a precious marker to evaluate and follow up the severity of aortic valve stenosis.

Impaired right ventricular functions in metabolic syndrome patients with preserved left ventricular ejection fraction.

OBJECTIVES Metabolic syndrome (MetS) has been shown to be independently associated with increased risk for incident heart failure and coronary artery disease. We investigated whether there was deterioration in right ventricular functions in MetS patients with preserved left ventricular functions and its association with the number of MetS components. STUDY DESIGN The study included 192 consecutive patients (148 women, 44 men; mean age 54.3 ± 8.5 years) with the diagnosis of MetS based on the NCEP-ATP III criteria and 20 healthy controls (12 women, 8 men; mean age 51.6 ± 8.4 years). All subjects underwent conventional and tissue Doppler (TDI) echocardiography to assess left and right ventricular functions, including right ventricular myocardial performance index (MPI) and tricuspid annular plane systolic excursion (TAPSE). RESULTS The number of MetS components were three in 43.8%, four in 31.3%, and five in 25% of the patients. Right ventricular TDI-derived MPI was higher in patients with MetS compared to controls [median 0.5 (range 0.2-3.3) vs. 0.3 (0.1-0.7), p=0.000]. This was possibly due to significantly shortened right ventricular ejection time in MetS patients (p<0.05). Although TAPSE was within the normal range in MetS patients, it was significantly decreased compared to controls (p=0.000), accompanied by significantly lower TDI-derived S wave, E wave, and E/A ratio (p=0.000). None of the MetS components were significantly correlated with right ventricular TDI-derived MPI. There was no association between the number of MetS components and echocardiographic parameters. CONCLUSION Our findings show that, despite preserved left ventricular systolic functions, both systolic and diastolic functions of the right ventricle deteriorate in MetS patients.

Thymosin beta 4 is associated with collateral development in coronary artery disease

Abstract Objectives: Thymosin beta 4 (Tβ4) plays an essential role in cardiac vessel development and is currently being developed as a therapeutic agent for the treatment of coronary artery disease (CAD) in some experimental studies. Thus, we aimed to investigate the association of serum Tβ4 levels and collateral formation in patients presenting with severely stenotic CAD. Methods: Thirteen patients with poor collateral development and 16 age- and sex-matched patients with good collateral development who had ≥ 95% stenosis in at least one major coronary artery on coronary angiogram (CAG) were enrolled in the study. The Gensini score was calculated for each patient by using CAG results. Collateral development was classified according to the Cohen-Rentrop method. Serum Tβ4 levels were measured with enzyme-linked immune sorbent assay. Results: There were no statistically significant differences between the two groups in regard to clinical and laboratory characteristics of the patients except for Tβ4 levels. The Tβ4 levels in the well-collateralized study group were found to be significantly higher than those of the poorly collateralized study group and serum Tβ4 levels were positively correlated with the collateral development. Conclusions: Our findings suggest that serum Tβ4 levels are significantly associated with the collateral development in severe CAD.

Effect of reperfusion therapy on index of myocardial performance in acute myocardial infarction: thrombolytics versus primary angioplasty

It is known that primary angioplasty is more effective than thrombolytic therapy for the treatment of ST-segment elevation acute myocardial infarction. The aim of the present study is to compare the effects of the two strategies on the left ventricular functions using the Tei index (a combined myocardial performance index). Of 81 patients (11 female, mean age 52.7 ± 11.9 years, and 70 male, mean age 54.8 ± 11.5 years) matching the selection criteria, 41 patients were treated by primary percutaneous transluminal coronary angioplasty and stenting (group A, 41 patients) and 40 patients were treated by thrombolytic agents (streptokinase) (group B, 40 patients). All patients underwent a complete two-dimensional transthoracic echocardiographic and Doppler study in the left lateral decubitus position from multiple windows. There was no significant difference between the two groups in isovolumetric contraction time and ejection time. Isovolumetric relaxation time was 95.2 ± 18.4 in group A and 116.2 ± 28.1 in group B (P = 0.001) and the Tei index was 0.51 ± 0.12 in group A and 0.59 ± 0.16 in group B (P = 0.019). Isovolumetric relaxation time and Tei index were significantly higher in group B. Primary angioplasty is superior to thrombolytic therapy as assessed by the Tei index even in the first 3 h, with no apparent change in systolic function.

An invasive but simple and accurate method for ascending aorta-femoral artery pulse wave velocity measurement.

Abstract Introduction. Pulse wave velocity (PWV) is an emerging predictor in the assessment of cardiovascular risk in diseased and healthy populations. We suggest a novel method for the accurate measurement of PWV. Method. PWV is calculated from pulse transit time using two separate pulse recordings over a known distance. 8F sheaths were placed in the right femoral arteries and routine coronary angiographies were performed with 5F diagnostic catheters. Ascending aorta pressures were measured with right diagnostic catheter tip in the ascending aorta and synchronous femoral artery pressures were measured with the sheath in the femoral artery. The distance between the two pressure sites was calculated as follows: total length of the right diagnostic catheter−length of the catheter outside the sheath−Sheath length. Results. We evaluated the PWV measured using the catheter method in 24 subjects. PWV correlated positively and independently with age (p = 0.004), coronary artery disease (p = 0.04), ascending aorta systolic pressure (p = 0.006), femoral artery systolic pressure (p = 0.008), ascending aorta pulse pressure (p = 0.003) and femoral artery pulse pressure (p = 0.04). In coronary artery disease patients, the mean PWV value was significantly higher than in patients with normal coronary arteries (12.61 ± 6.31 m/s vs 7.58 ± 2.26 m/s p = 0.04). Conclusion. We describe a novel and accurate but invasive method for measurement of PWV. Our results may serve as a reference for non-invasive assessment of aorta–femoral artery PWV.

Thymosin beta4 levels after successful primary percutaneous coronary intervention for acute myocardial infarction.

OBJECTIVES Thymosin beta4 (Tβ4) has been shown to have an important role in healing of damaged tissues and promoting cardiomyocyte survival in acute coronary syndromes. We evaluated endogenous Tβ4 levels in patients presenting with ST-elevation acute myocardial infarction (STEMI) before and after successful primary percutaneous coronary intervention (PCI). STUDY DESIGN The study included 24 consecutive patients (7 females, 17 males; mean age 55.0±10.9 years) who underwent successful primary PCI for STEMI and 24 age- and sex-matched healthy controls (13 females, 11 males; mean age 57.5±11.7 years) with angiographically normal coronary arteries. To determine Tβ4 levels, blood samples were obtained from STEMI patients on admission and 48 hours after successful PCI, and from controls immediately after coronary angiography. RESULTS Compared to controls, baseline levels of high-density lipoprotein cholesterol (46.2±8.9 vs. 34.2±7.2 mg/dl, p<0.001) and Tβ4 (2.9±1.5 vs. 1.5±1.0 µg/ml, p<0.001) were significantly lower, and white blood cell counts (7.6±2.2 vs. 11.4±3.0 10³/µl, p<0.001) were significantly higher in the STEMI group. After 48 hours of PCI, the mean Tβ4 level increased significantly to 2.3±0.8 µg/ml (p<0.001) and became similar to that of the control group (p=0.068). There was a significant negative correlation between serum Tβ4 and white blood cell count (r=-0.347, p=0.016). CONCLUSION Considering the significant increase in serum Tβ4 levels following successful primary PCI in patients with STEMI, Tβ4 may prove to be a new marker in the assessment of reperfusion success in addition to those used currently.

Association between plasma asymmetrical dimethylarginine activity and saphenous vein graft disease in patients with coronary bypass.

BackgroundCoronary vein graft disease is an important contributor to the morbidity after coronary artery bypass graft surgery. Graft occlusion is a serious complication, which limits the use of the saphenous vein as a coronary bypass conduit. Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and it reduces the bioavailability of nitric oxide and begets endothelial dysfunction. The goal of this study was to examine the association between plasma ADMA activity and saphenous vein graft disease. MethodsOne hundred and three patients were enrolled in this study. Group 1 consisted of 42 patients (13 female, 29 male) who had diseased saphenous vein grafts and group 2 consisted of 61 patients (10 female, 51 male) with nondiseased saphenous vein grafts. ADMA activity was measured by the enzyme-linked immunosorbent assay kit. ResultsMean ADMA activity in group 1 was significantly higher than in group 2 (2.0±0.6 vs. 1.1±0.5 μmol/l, P<0.001, respectively). Mean platelet volume was also significantly higher in group 1 than in group 2 (8.7±1.5 vs. 8.2±0.6 fl, P=0.03, respectively).In a multivariate linear regression analysis, ADMA activity (&bgr;=2.902, P<0.001) and mean platelet volume (&bgr;=0.595, P=0.03) were found to be independent predictors of saphenous vein graft disease. ConclusionOur results showed that ADMA activity was higher in patients with saphenous vein graft disease. Increased ADMA activity might lead to the acceleration of saphenous vein graft disease. ADMA may be a precious marker for detecting late saphenous vein graft patency.

Resolution of late sirolimus-eluting stent thrombosis after tirofiban treatment

A 40-year-old male patient was admitted to the hospital with acute chest pain. A sirolimus-eluting stent (SES) had been deployed to the circumflex artery (Cx) 3 years before. Now, inferior ST-segment elevations were observed and coronary angiography revealed stent thrombosis with distal TIMI 3 grade flow in the Cx. Tirofiban infusion was administered and the control angiography 2 days later revealed complete resolution of the thrombus. Stent thrombosis is a rare but usually poor prognostic event, frequently associated with large myocardial infarction (MI) or death. Very late drug-eluting stent (DES) thrombosis remains a major problem of interventional cardiology due to its high morbidity and mortality. We conclude that tirofiban may be an interesting candidate drug for treatment of very late stent thrombosis.