Nitric oxide mediated effects of nebivolol in myocardial infarction: the source of nitric oxide.

OBJECTIVE: After MI pathological LV remodeling is one of the major causes of death. We previously showed the NO mediated beneficial effects of nebivolol in rat MI model, in this study we aimed to evaluate the NOS related mechanisms in this phenomenon. MATERIALS AND METHODS: Rats were divided into four groups: sham operated (sham-control), MI-induced (MI-control), immediate nebivolol loaded (MI-neb1), orally nebivolol treated (MI-neb2). MI was induced by the ligation of the LAD. Loading dose of nebivolol (0.1 mg/kg) was administrated i.v. during reperfusion and continuation dose was administrated orally (2 mg/kg) by gastric gavages once daily. NOS related mechanisms were assessed either in acute (2nd day) and sub-acute (28th day) period of MI by histologic, hemodynamic and biologic studies. RESULTS: Compared to MI-control rats, physiological functions of LV (LVEDP, Δ±dp/dt) were prevented in both nebivolol treated groups. Improvements in anatomical parameters (LEV, HW, LVW/HW) were consistent with functional improvement too. Moreover, oxidative (characterized by decreased MDA and increased SOD levels) and nitrosative (characterized by decreased ONOO- levels) damage were limited in these groups. Compared to MI-control rats, most marked change was seen in the nNOS labelling in the nebivolol treated groups. The decrease in iNOS labelling was also prominent in these groups too. CONCLUSIONS: NOS mediated mechanisms of nebivolol can be summarized as: 1) diminishing iNOS expression together with restoration of MI induced eNOS activation both in vascular bed and myocytes at the acute period of MI, and 2) prevention of deterioration in nNOS expression in myocardial cells at the sub-acute period of MI.

The relationship between T-wave peak-to end interval and ST segment recovery on intracoronary ECG during primary PCI.

OBJECTIVE: T-wave peak to end interval (TPE) is a measure of repolarization dispersion, which has been reported as a major arrhythmogenic factor post acute myocardial infarction. The aim of our study was to investigate the changes in TPE in this patient population with regard to peri-procedural intracoronary ECG findings. PATIENTS AND METHODS: Forty-four patients (34 male and mean age of 54.9 ± 10.9 years) with acute STEMI were included. Intracoronary ECG was performed during primary PCI. TPE indices were calculated before and after the procedure. Measurement of the intracoronary ST-segment was carried out before and just after coronary blood flow was established in the infarct related artery. Intracoronary ST-segment resolution (IC-STR) was defined as ≥ 1 mm compared to baseline. RESULTS: There was no difference with respect to baseline characteristics when patients with IC-STR were compared with patients without IC-STR. TPE values decreased significantly after primary PCI in patients with IC-STR (80.9 ± 22.8 ms vs. 65.8 ± 14.4 ms; p < 0.001) whereas they did not change significantly after PCI in patients without IC-STR (79.2 ± 20.9 ms vs. 68.5 ± 16.3 ms; p = 0.18). CONCLUSIONS: TPE measured from surface ECG recordings is significantly reduced in STEMI patients with successful reperfusion after primary PCI, as determined by IC-ECG recordings.

Endothelial dysfunction in renal transplant patients is closely related to serum cyclosporine levels.

BACKGROUND: Cyclosporine (CsA), one of the standard agents used in renal transplant recipients, has been considered to cause endothelial dysfunction and to contribute to arterial complications posttransplant. Since concentration-dependent effects of CsA on endothelial functions in humans have not been examined, this study was performed to investigate this relationship. METHODS: Fifteen renal transplant patient and 20 healthy subjects (controls) were evaluated for brachial artery endothelial function using high-resolution vascular ultrasound just before the CsA dosage (baseline) and at the second hour after the administration. Endothelium-dependent and -independent vasodilatations (EDD and EID, respectively) were assessed by establishing of the responses to reactive hyperemia and by using sublingual nitroglycerine, respectively. CsA levels were assessed at baseline and at second hour, times when performing brachial artery measurements. RESULTS: There were no significant differences between recipients and controls with respect to atherosclerosis risk factors. Mean EDD of recipients at baseline times were significantly less than those in controls (9.1% +/- 5.5% vs 15.2% +/- 7.2%, respectively; P < .001). CsA levels at trough and at second hour were 153.9 +/- 74.8 ng/mL and 646.8 +/- 163.2 ng/mL, respectively (P < .0001). Recipient, EDD at second hour was significantly reduced compared to baseline values (5.3% +/- 3.6% vs 9.1% +/- 5.5% respectively; P = .014) while changes in EID and in the diameter of the brachial artery between baseline and second hour were insignificant. CONCLUSION: Endothelial dysfunction evaluated by brachial ultrasound in renal transplant recipients is closely related to CsA levels. It is more pronounced at 2 hours after CsA dosage, at the time of peak drug levels.

Does the endothelial function change in renal transplant patients with longer duration of exposure and with higher cumulative doses of cyclosporine?

OBJECTIVE: Administration of cyclosporine (CsA) is one potential cause of endothelial dysfunction in renal transplant patients. We sought to investigate endothelial functional changes with respect to the cumulative dose and duration of exposure to CsA. METHODS: Sixty-six renal recipients and 25 healthy controls were included in the study. The recipients were classified according to their time of CsA exposure: group 1 (0 to 36 months); group 2 (36 to 72 months); and group 3 (over 72 months). Endothelial function of the brachial artery was evaluated using high-resolution vascular ultrasound. Endothelium-dependent and -independent vasodilatation (EDD and EID, respectively) were assessed by assessing the responses to reactive hyperemia and using sublingual isosorbide dinitrate (ISDN), respectively. RESULTS: There were no statistically significant differences between the groups with regard to their demographic, clinical, and most biochemical characteristics. Baseline measurements of the diameter of the brachial artery were similar in all groups. The values of mean brachial artery EDD and EID responses in groups 1, 2, and 3 were less than those in the control group (P < .05, P < .05, and P < .05, respectively). Mean brachial artery EDD and EID in group 1 were significantly impaired compared to groups 2 and 3 (for EDD: P < .05 and P < .05, respectively; for EID: P < .05 and P < .05, respectively). In contrast there was no difference between groups 2 and 3 with respect to these parameters. There were mild to moderate positive correlations between the cumulative doses of CsA and EDD and EID (r = .26 and r = .52, P < .05, respectively). CONCLUSION: Endothelial dysfunction was more prominent in the first 36-month period than later despite the longer exposure to and higher cumulative doses of CsA. This finding may reflect an extended effect of the uremic state on endothelial function or more intense doses of CsA in early posttransplant period.

Impaired endothelium-dependent flow-mediated dilation in Behçet's disease: more prominent endothelial dysfunction in patients with vascular involvement.

Brachial artery endothelial dysfunction was shown previously in a small group of Behçet's disease (BD) patients. This study aimed to compare the endothelial function in BD patients with and without vascular involvement. The study group consisted of 25 BD patients with vascular involvement, 25 BD patients without any vascular disease and 46 healthy controls. Brachial artery flow-mediated (endothelium-dependent) dilation (FMD), nitroglycerine-induced dilation and carotid artery intima-media thickness were measured. FMD was impaired in patients with BD (10.41 +/- 3.85%) compared to healthy controls (14.41 +/- 3.39%, p < 0.001). FMD was significantly lower in BD patients with vascular involvement (8.80 +/- 3.63%) than those without any vascular disease (12.02 +/- 3.43%, p = 0.003). This study reveals that endothelial dysfunction documented by brachial artery FMD is a feature of BD, and it is more prominent in patients with vascular involvement.

The short-term effects of cilazapril on left ventricular diastolic function.

To investigate the short-term effects of cilazapril on left ventricular diastolic functions in patients with essential hypertension, 20 patients with mild-to-moderate essential hypertension were evaluated. Following 2 weeks of placebo washout, all patients underwent blood pressure determination and echo-Doppler ultrasonography recordings. Cilazapril, 2.5 mg, was given to all patients, and blood pressure was determined. Echo Doppler ultrasonography recordings were repeated 3 h after drug therapy. The investigated diastolic function parameters were peak and mean velocities of mitral E and A waves, ratio of peak E to peak A, and acceleration and deceleration rates of E and A waves. Both systolic and diastolic blood pressure changes were insignificant. The E wave peak and mean velocities were significantly increased (p = 0.006 and 0.02, respectively), and the A wave peak and mean velocities were significantly reduced (p = 0.006 and 0.02, respectively) after cilazapril therapy. The ratio of peak E to peak A velocity was also found to be increased following cilazapril therapy (p = 0.006). It is to be concluded that the immediate improvement of left ventricular diastolic functions after cilazapril therapy despite the lack of blood pressure decrease is probably a result of the inhibition of tissue angiotensin-converting enzyme and/or other local humoral factors, but this needs to be further investigated.

Impaired brachial endothelial function in patients with primary anti-phospholipid syndrome.

Although the precise pathophysiology of thrombosis is unknown in primary anti-phospholipid syndrome (PAPS), it is assumed that autoantibodies developed against endothelial cells and platelets might be one of the primary mechanisms. However, whether interaction between autoantibodies and endothelium leads to an impaired vasodilator response has not been investigated yet. In this study, we aimed to investigate the endothelial functions in patients with PAPS. Thirty-one patients with PAPS (22 female, nine male, mean age: 34.6+/-8.9 years) and 27 age- and sex-matched, healthy controls were included in the study. Brachial artery responses to reactive hyperaemia (endothelium-dependent dilatation) [EDD] and sublingual nitroglycerine (endothelium-independent dilatation) [EID] were measured by using high-resolution vascular ultrasound both in patients with PAPS and in the controls. The results were expressed as percentage of change in baseline values. Regarding cardiovascular risk factors, there was no significant difference between the two groups. EDD in patients with PAPS was significantly lower than those of controls (6.9+/-4.9 vs. 14.8+/-4.1%; p<0.0001). EID measurements were not significantly different between the groups. In the PAPS group, EDD in patients with arterial involvement (17 patients) was significantly lower than those of patients with venous involvement (12 patients) (4.6+/-3.9 vs. 7.4+/-4.1%; p = 0.02). This study showed that endothelial functions determined by using brachial artery ultrasound were impaired in patients with PAPS, and this was more prominent in the subgroup of patients with arterial involvement compared to patients with venous involvement.

Determination of endothelial function and early atherosclerotic changes in healthy obese women.

The aim of this study was to determine the associations between vascular endothelial function, intima-media thickness (IMT) of the common carotid artery and anthropometric/metabolic parameters in healthy obese women without obesity-related metabolic complications and age-matched healthy lean controls. Twenty-four obese [body mass index (BMI) > 30 kg/m2; age 31.4 +/- 7.4 yr] and 14 lean (BMI < 24 kg/m2; age 30.5 +/- 7.2 yr) women were studied. All of the subjects had normolipemia. Insulin resistance was calculated according to the homeostasis model assessment (HOMA) formula. Endothelial function was measured by flow-mediated dilation (FMD) of the brachial artery. IMT of the common carotid artery was calculated from high-resolution ultrasound imaging of the two common carotid arteries. Obese and lean women were matched with respect to age, smoking status, blood pressure, glucose, insulin concentrations and HOMA. IMT of common carotid artery was significantly higher (0.56 +/- 0.09 vs 0.45 +/- 0.06 mm, p < 0.001) and FMD (percentage of change from baseline) was significantly lower (13.3 +/- 6.5% vs 25.2 +/- 13.9%,p < 0.001) in the obese subjects. Lipid profile, blood pressure, indirect measurement of insulin resistance, leptin concentrations and anthropometric parameters did not predict the FMD or IMT in the obese and lean groups. It is concluded that even in healthy obese women with a normal metabolic profile, deterioration in endothelial function and early atherosclerotic changes are evident compared with healthy lean counterparts. Some undetermined factors in our study other than obesity-related well-known risk factors could be responsible for this observation.