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Biomedical subjects

Ali Erdogan

Publications and source records attributed to Ali Erdogan.

32 records · Page 2Linked to original sources
PubMed2004

Basic fibroblast growth factor-induced endothelial proliferation and NO synthesis involves inward rectifier K+ current.

OBJECTIVE: Inward rectifier K+ currents (K(ir)) determine the resting membrane potential and thereby modulate essential Ca2+-dependent pathways, like cell growth and synthesis of vasoactive agents in endothelial cells. Basic fibroblast growth factor (bFGF) acts as a vasodilatator and angiogenic factor. Therefore, we investigated the effect of bFGF on K(ir) and assessed the role in proliferation and nitric oxide (NO) formation of endothelial cells. METHODS AND RESULTS: Using the patch-clamp technique, we found characteristic K(ir) in human umbilical cord vein endothelial cells (HUVEC), which were dose-dependently blocked by barium (10 to 100 micromol/L). Perfusion with bFGF (50 ng/mL) caused a significant increase of K(ir), which was blocked by 100 micromol/L barium (n=18, P<0.01). The bFGF-induced HUVEC proliferation was significantly inhibited when using 50 to 100 micromol/L barium (n=6; P<0.01). NO production was examined using a cGMP radioimmunoassay. bFGF caused a significant increase of cGMP levels (n=10; P<0.05), which were blocked by barium. CONCLUSIONS: Modulation of K(ir) plays an important role in bFGF-mediated endothelial cell growth and NO formation.

Barium↗
PubMed2004

Use of gadobutrol in coronary angiography.

Gadobutrol was used in coronary angiography in three patients. All three patients had a substantially increased risk of developing renal complications with iodinated contrast agents. Gadobutrol was well tolerated in all three patients without any complications. The quality of the coronary angiograms was good.

Adult↗
PubMed2004

Statins prevent oxidized low-density lipoprotein- and lysophosphatidylcholine-induced proliferation of human endothelial cells.

The proliferation of endothelial cells is induced by oxidized low-density lipoprotein (oxLDL) and its major component, lysophosphatidylcholine (LPC). The aim of this study was to investigate the effect of statins on the proliferation of endothelial cells derived from human umbilical cord veins (HUVEC). Cerivastatin, simvastatin and fluvastatin caused a dose-dependent inhibition of endothelial cell growth (n=12; P<.01) when using cell counts and [3H]-thymidine incorporation, respectively. The strongest inhibition of HUVEC proliferation was achieved at statin concentrations of 0.1 micromol/l (cerivastatin), 2.5 micromol/l (simvastatin) and 1 micromol/l (fluvastatin). Cell counts were significantly reduced from 22937+/-280.6 (control) to 7791+/-133.6 (cerivastatin), 7292+/-146.6 (simvastatin) and 6792+/-135.5 (fluvastatin) (n=12; P<.01). Interestingly, cell proliferation induced by oxLDL (10 microg/ml) and LPC (20 micromol/l) could be effectively prevented using statins at concentrations between 0.01 and 0.1 micromol/l (cerivastatin), 1 and 2.5 micromol/l (simvastatin) and 0.25 and 1 micromol/l (fluvastatin). This effect of the statins was abolished by preincubation with mevalonate (500 micromol/l). Our results demonstrate an interesting direct effect of statins on the proliferation of human endothelial cells induced by oxLDL and LPC, which may be beneficial to prevent vascular effects of these atherogenic lipids.

Cell Division↗
PubMed2004

Lysophosphatidylcholine-induced modulation of Ca(2+)-activated K(+)channels contributes to ROS-dependent proliferation of cultured human endothelial cells.

Proliferation of endothelial cells plays a crucial role in the process of atherosclerotic plaque destabilization. The major component of oxidized low-density lipoprotein lysophosphatidylcholine (LPC) has been shown to promote endothelial proliferation by increasing the production of reactive oxygen species (ROS). Since K(+) channels are known to control the cell cycle, we investigated the role of Ca(2+)-activated K(+) channels (BK(Ca)) in the regulation of LPC-induced endothelial proliferation and ROS generation. A significant increase of cell growth induced by LPC (20 micromol/l; cell counts (CCs): +87%, thymidin incorporation: +89%; n = 12, P < 0.01) was observed, which was inhibited by the BK(Ca) inhibitor iberiotoxin (IBX; 100 nmol/l), by the NAD(P)H-oxidase inhibitor diphenyleneiodonium (5 micromol/l) and by transfection with antisense (AS) oligonucleotides against NAD(P)H oxidase, whereas N(G)-monomethyl-l-arginine (l-NMMA) further increased LPC-induced cell growth. Using the patch-clamp technique a significant increase of BK(Ca) open-state probability (control: 0.004 +/- 0.002; LPC: 0.104 +/- 0.035; n = 21, P < 0.05) by LPC was observed. Using dichlorofluorescein fluorescence microscopy a significant increase of ROS induced by LPC was reported, that was blocked by IBX and Ca(2+) antagonists. Intracellular Ca(2+) measurements revealed a capacitative Ca(2+) influx caused by LPC. Bioactivity of nitric oxide (NO) was measured using a [(3)H]-cGMP radioimmunoassay. LPC significantly decreased acetylcholine-induced NO synthesis. LPC significantly increased cGMP levels in endothelial cells transfected with AS, which was blocked by IBX. In conclusion, our results demonstrate that LPC activates BK(Ca) thereby increasing ROS production which induces endothelial proliferation. In addition LPC-induced BK(Ca)-activation contributes to increased cGMP levels, if ROS production is prevented by AS.

Calcium↗
PubMed2004

Dose-dependent activation of Ca2+-activated K+ channels by ethanol contributes to improved endothelial cell functions.

BACKGROUND: Regular moderate alcohol (EtOH) intake seems to protect against both coronary artery disease and ischemic stroke, whereas the risk increases with heavy EtOH consumption. Effects of EtOH on endothelial cell function may be relevant to these disparate effects. Potassium channels play an important role in the regulation of endothelial cell functions. Therefore, we investigated whether Ca-activated K channels (BKCa) are modulated by EtOH. Furthermore, we examined whether EtOH-induced changes of endothelial nitric oxide (NO) formation and cell proliferation are due to BKCa activation. METHODS: The patch-clamp technique was used to investigate BKCa activity in cultured human umbilical vein endothelial cells (HUVEC). NO formation was analyzed by using the fluorescence dye 4,5-diaminofluorescein. Endothelial proliferation was examined by using cell counts and measuring [H]thymidine incorporation. RESULTS: EtOH dose-dependently (10-150 mmol/liter) modulated BKCa-activity, with the highest increase of open-state probability at a concentration of 50 mmol/liter (n = 13; p < 0.05). Inside-out recordings revealed that this effect was due to direct BKCa activation, whereas open-state probability was not changed in cell-attached recordings after pertussis toxin preincubation. EtOH (10 and 50 mmol/liter) caused a significant increase of NO levels, which was blocked by the highly selective BKCa inhibitor iberiotoxin (100 nmol/l; n = 30; p < 0.05). Higher concentrations of EtOH (100 and 150 mmol/liter) significantly reduced NO synthesis (n = 30; p < 0.05). Both methods revealed a significant increase of HUVEC proliferation, which was inhibited by iberiotoxin (n = 30; p < 0.05). At a concentration of 150 mmol/liter, EtOH caused a significant reduction of endothelial proliferation. CONCLUSIONS: EtOH directly activates BKCa in HUVEC, leading to an increase of endothelial proliferation and production of NO. These results indicate a possible beneficial effect of low-dose EtOH on endothelial function, whereas higher concentrations must be considered as harmful.

Cell Proliferation↗
PubMed2004

Risk stratification using heart rate turbulence and ventricular arrhythmia in MADIT II: usefulness and limitations of a 10-minute holter recording.

BACKGROUND: We evaluated the usefulness of heart rate turbulence (HRT) parameters and frequency of ventricular premature beats (VPBs) for risk-stratifying postinfarction patients with depressed left ventricular function enrolled in Multicenter Automatic Defibrillator Trial II (MADIT II). METHODS: In 884 MADIT II patients, 10-minute Holter monitoring at enrollment was used to evaluate HRT parameters and frequency of VPBs. The primary endpoints were defined as all-cause mortality in patients randomized to conventional treatment and as appropriate therapy for ventricular tachycardia or fibrillation in patients randomized to implantable cardioverter defibrillator (ICD) therapy. RESULTS: The median turbulence slope was lower in patients who died in comparison to survivors in the conventional arm (2.3 vs 4.5 ms/RR; P < 0.05); but it was not a significant predictor of mortality after adjustment for clinical covariates (age, ejection fraction, beta-blocker use, and BUN levels). There was no association between HRT parameters and arrhythmic events in ICD patients. Conventionally treated patients who died and ICD patients who had appropriate ICD therapy had significantly more frequent VPBs than those without such adverse events. After adjustment for clinical covariates, frequent VPBs>3/10 min were associated with death in the conventional arm (HR = 1.63; P = 0.070) and were predictive for appropriate ICD therapy in the ICD arm (HR = 1.75; P = 0.003). CONCLUSION: In postinfarction patients with severe left ventricular dysfunction, frequent VPBs are associated with increased risk of mortality and with appropriate ICD therapy. HRT obtained from 10-min Holter ECG showed a trend toward the association with mortality in univariate analysis but HRT parameters were not predictive of the outcome in multivariate analyses.

Adult↗
PubMed2004

The K+-channel opener NS1619 increases endothelial NO-synthesis involving p42/p44 MAP-kinase.

Ca(2+)-activated K(+) channels with large conductance (BK(Ca)) have been shown to play an important role in the regulation of vascular tone. We examined the role of the p42/p44 MAP-kinase (p42/p44(MAPK)) on nitric oxide (NO) production in human endothelial cells induced by the BK(Ca)-opener NS1619. Using DiBAC-fluorescence imaging a concentration-dependent (2.5-12.5 microM) hyperpolarization induced by NS1619 was observed. A significant increase of intracellular Ca(2+)-concentration by NS1619 was seen using Fura-2-fluorescence-imaging, which was blocked by 2-APB, or reduction of extracellular Ca(2+) (n=30; p<0.05). A cGMP-radioimmunoassay was used to examine NO synthesis. NS1619 significantly increased cGMP levels which was inhibited by LNMMA, iberiotoxin, BAPTA, 2-APB, reduction of extracellular Ca(2+), PD 98059, or U0126 (cGMP (pmol/mg protein): NS1619 3.25 +/- 0.85; NS1619 + L-NMMA 0.86 +/- 0.02; NS1619 + iberiotoxin 0.99 +/- 0.09; NS1619 + BAPTA 0.93 +/- 0.29; NS1619 + 2-APB 0.99 +/- 0.31; NS1619 + Ca(2+)-reduction 1.17 +/- 0.06; NS1619 + PD98059 1.06 +/- 0.49; NS1619 + U0126 1.10 +/- 0.24; n=10; p<0.05). The phosphorylation of eNOS and p42/p44(MAPK) was examined by immunocytochemistry. Phosphorylation of p42/p44(MAPK) was significantly increased after 10 minutes of NS1619 stimulation, whereas eNOS phosphorylation was not changed over a period of 1 to 30 minutes. NS1619-induced hyperpolarization was not affected by treatment with PD 98059 or U0126. Additionally, NS1619 inhibited endothelial proliferation involving a NO-dependent mechanism. Our data demonstrate that NS1619 causes a transmembrane Ca(2+)-influx leading to an increased NO production involving p42/p44(MAPK). This rise of NO formation is responsible for the NS1619 induced reduction of endothelial cell growth.

Benzimidazoles↗
PubMed2003

Pulmonary vein diameter reduction after radiofrequency catheter ablation for paroxysmal atrial fibrillation evaluated by contrast-enhanced three-dimensional magnetic resonance imaging.

BACKGROUND: Radiofrequency catheter ablation (RFCA) is a promising intervention to treat atrial fibrillation. However, pulmonary vein (PV) stenosis after RFCA has been reported. The aim of this study was to investigate the incidence and time course of pulmonary vein stenosis after RFCA within a period of 3 months. Contrast-enhanced magnetic resonance angiography (MRA) was used to visualize pulmonary veins and was compared with radiographic angiography. METHODS AND RESULTS: Forty-six consecutive patients with symptomatic paroxysmal atrial fibrillation had RFCA in the orifice of 138 pulmonary veins. Comparison of diameters measured in 44 untreated vessels either by radiographic angiography or with MRA established the reliability of MRA (r=0.934). MRA measurements revealed an incidence of relevant diameter reductions of > or =25% or stenosis of > or =50% after RFCA of 25 of 138 (18.1%) treated vessels 1 day and/or 3 months after ablation. A progression of diameter reduction after RFCA was observed in 8.3% (maximum 75%), whereas a regression was observed in 6.3% of treated PVs. Ablation at a radial angle of >180 degrees of a pulmonary vein orifice increased the risk of diameter reduction significantly compared with ablation at a radial angle < or =180 degrees (P=0.002). CONCLUSIONS: The occurrence and progression of PV stenosis is a potential significant complication of RFCA in the orifice of pulmonary veins. These findings may have an impact on the technical performance of this intervention. In addition, long-term studies will be necessary to evaluate lumen reduction over time. MRA is a noninvasive, reproducible imaging modality for this purpose.

Angiography↗
PubMed2003

Proportion of candidates for cardiac resynchronization therapy.

Biventricular pacing has been used as an adjunct to standard heart failure therapy in symptomatic patients with left bundle branch block (LBBB). Estimates of the number of patients for whom this treatment is appropriate are unavailable, but are of clinical and socioeconomic importance. LBBB combined with a low (< 0.35) ejection fraction was found in 7,121 consecutive patients referred for elective diagnostic angiography in 1996 through 2000 from a total population of about 125,000 residents. Patients with LBBB (n = 289, 4%) had lower ejection fractions (0.53 +/- 0.23) in comparison with patients without LBBB (P < 0.0001). The ejection fraction was < 0.35 in 558 (8%) patients. LBBB was combined with a low ejection fraction in 96 (1.4%) patients (i.e., 19 patients per year and about 15 patients per year per 100,000 residents). Of these 96 patients, 80 had normal sinus rhythm, 82 had mitral regurgitation (grade > II), 86 were < 75 years of age, and 68 had coronary artery disease. Holter recordings performed in 47 of 96 patients showed nonsustained VT in 28 (60%). LBBB, low ejection fraction, sinus rhythm, and age < 75 years were found in 71 (1%) patients (i.e., 11 patients per year per 100,000 residents). The prevalence of LBBB combined with severely impaired left ventricular ejection function is about 1-2% in patients who undergo cardiac catheterization. The authors estimate that biventricular pacing might be considered as an adjunct to standard heart failure therapy in five to ten patients per year per 100,000 residents in industrial countries. About half of these patients are potential candidates for implantation of cardioverter defibrillators combined with permanent pacing.

Aged↗
PubMed2003

Microwave, irrigated, pulsed, or conventional radiofrequency energy source: which energy source for which catheter ablation?

The aim of the study was to compare the diameter of endomyocardial lesions induced with the delivery of microwave, cooled, or pulsed energy versus conventional RF energy. In vitro tests were performed in fresh endomyocardial preparations of pig hearts in a 10-L bath of NaCl 0.9% solution at 37 degrees C and constant 1.5 L/min flow. Ablation 7 Fr catheters with 4-mm tip electrodes were used, except for the delivery of microwave energy. Energy delivery time was set to 60 s/50 W in all experiments. Cooled energy delivery was performed with a closed irrigation catheter. Pulsed energy delivery was performed using a special controller with a duty-cycle of 5 ms. Microwave energy was delivered with a 2.5-GHz generator and 10-mm antenna. Electrode temperature and impedance were measured simultaneously. After ablation, lesion length, width, and depth were measured with microcalipers, and volume calculated by a formula for ellipsoid bodies. Each energy delivery mode was tested in ten experiments. The deepest lesions were created with cooled energy delivery, and the largest volume by microwave energy delivery. Pulsed RF produced significantly deeper lesions than conventional RF energy delivery. Cooled or pulsed RF energy delivery created deeper transmural lesions than conventional RF. To create linear lesions at anatomically complex sites (isthmus), microwave energy seemed superior by rapidly creating deep and long lesions.

Animals↗
PubMed2003

Prospective randomized comparison of two defibrillation safety margins in unipolar, active pectoral defibrillator therapy.

Various techniques are used to establish defibrillation efficacy and to evaluate defibrillation safety margins in patients with an ICD. In daily practice a safety margin of 10 J is generally accepted. However, this is based on old clinical data and there are no data on safety margins using current ICD technology with unipolar, active pectoral defibrillators. Therefore, a randomized study was performed to test if the likelihood of successful defibrillation at defibrillation energy requirement (DER) + 5 J and + 10 J is equivalent. Ninety-six patients (86 men; age 61.0 +/- 10.3 years; ejection fraction 0.341 +/- 0.132; coronary artery disease [n = 65], dilated cardiomyopathy [n = 18], other [n = 13]) underwent implantation of an active pectoral ICD system with unidirectional current pathway and a truncated, fixed tilt biphasic shock waveform. The defibrillation energy requirement (DER) was determined with the use of a step-down protocol (delivered energy 15, 10, 8, 6, 4, 3, 2 J). The patients were then randomized to three inductions of ventricular fibrillation at implantation and three at predischarge testing with shock strengths programmed to DER + 5 J at implantation and + 10 J at predischarge testing or vice versa. The mean DER in the total study population was 7.88 +/- 2.96 J. The number of defibrillation attempts was 288 for + 5 J and 288 for + 10 J. The rate of successful defibrillation was 94.1% (DER + 5 J) and 98.9% (DER + 10 J; P < 0.01 for equivalence). Charge times for DER + 5 J were significantly shorter than for DER + 10 J (3.65 +/- 1.14 vs 5.45 +/- 1.47 s; P < 0.001). A defibrillation safety margin of DER + 5 J is associated with a defibrillation probability equal to the standard DER + 10 J. In patients in whom short charge times are critical for avoidance of syncope, a safety margin of DER + 5 J seems clinically safe for programming of the first shock energy.

Defibrillators, Implantable↗
PubMed2003

Quality-of-life in patients with paroxysmal atrial fibrillation after catheter ablation: results of long-term follow-up.

Paroxysmal atrial fibrillation (PAF) significantly impairs patients' quality-of-life (QOL). The effect on QOL of recently developed ablation techniques with curative intention has not been studied. Thirty patients (21 men, age 54.1 +/- 9.5 years) with PAF (duration 5.6 +/- 5.2 years) who failed antiarrhythmic (3.8 +/- 1.2 trials) drug therapy underwent catheter ablation. The follow-up time was 33.9 +/- 11 months. QOL was assessed preablation, 3, 6, 9, 12, 24, and 36 months after catheter ablation. The Medical Outcomes Survey Short-Form (SF-36), scored on a 0-100 scale for each of eight domains: bodily pain, general health, mental health, physical functioning, role-emotional, role-physical, social functioning, and vitality, was used. Simultaneously, patients filled out a symptom-specific checklist (SSC) with seven clinical items scored 1-4 (1 best): dyspnea, nausea, palpitations, anxiety, syncope, presyncope, and NYHA classification. Patients with successful catheter ablation had a significant benefit in seven of eight subscales while patients with recurrence had an impact on QOL in two of eight subscales. Using SSC, a successful ablation influenced scores in all seven items while patients with recurrence had a significant change of clinical symptoms in only one item, anxiety. The subscales of the study group compared to a healthy population show higher scores after 24 months of follow-up. Patients with PAF experience a significant improvement in QOL after a successful catheter ablation. In contrast, in patients with recurrence of PAF the QOL showed improvement to a lesser extent and patients experienced ongoing symptoms.

Atrial Fibrillation↗
PubMed2002

Shock coordinated with high power of morphology electrogram improves defibrillation success in patients with implantable cardioverter defibrillators.

Animal studies have suggested that the success of defibrillation may depend on the properties of VF waveform obtained from the morphology electrogram (ME) at the time of the shock. The reliable identification of depolarization events in the fibrillatory signal can be achieved using adaptive estimation of the instantaneous signal power (P). The aim of this study was to investigate if a high P of the ME (P(ME)) was related to ventricular DFT and if the upslope in ME can be associated with the depolarization event. A total of 575 VF (mean duration 10 s) episodes recorded and stored during ICD implantation in 77 patients with ventricular arrhythmias were used for analysis. The DFT was defined using a double step-down test. The values of P(ME) immediately before pulse delivery (P(shock)) and shock outcomes were registered. The differences between P(shock) of successful and failed defibrillation were tested with the Mann-Whitney U test. The relationship between individual medians of P(shock) (P(med)) and DFT was analyzed using the Kruskall-Wallis H-test. The coincidence between identified depolarization and upslope in ME was tested using the chi-square test. A P value of 0.05 was set for an error probability. The P(shock) in case of failed defibrillation was significantly lower than P(shock) in successful cases by the pulses of any strength (P < 0.001). The test revealed a significant inverse correlation between P(med) and DFT with P < 0.001. The depolarization corresponded to the upslope of ME in 85% of cases. This study demonstrated that a high value of instantaneous power of ME indicates the optimal time for shock delivery. The implementation of this algorithm in ICDs may improve the defibrillation efficacy.

Algorithms↗