Vitamin C attenuates methotrexate-induced oxidative stress in kidney and liver of rats.

Like several other anticancer drugs, methotrexate (MTX) causes side effects, such as neuropathic pain, hepatotoxicity, and nephrotoxicity. Abnormal production of reactive oxygen species has been suspected in the pathophysiology of MTX-induced hepatorenal toxicity. Therefore, the aim of this study was to investigate the probable protective role of vitamin C (Vit C) on oxidative stress induced by MTX in the liver and kidney tissues of rats. A total of 32 rats were randomly and equally divided into four groups. The first group served as the control group. The second group received a single dose of 20 mg/kg of MTX intraperitoneally. To demonstrate our hypothesis, the third and the fourth groups received 250 mg/kg of Vit C for 3 days by oral gavage, with or without MTX treatment. At the end of the study, the liver and kidney tissues of the rats were collected and examined using histology. Both the tissues were assayed for malondialdehyde concentration and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities. In hepatic and renal tissues, lipid peroxidation levels were increased, whereas SOD, CAT, and GSH-Px levels were decreased by MTX. All parameters, including CAT levels in hepatic tissue, were significantly restored after the administration of Vit C for 3 days. Similar to the biochemical findings, evidence of oxidative damage was examined in both types of tissues by histopathological examination. From the results of this study, we were able to observe that Vit C administration modulates the antioxidant redox system and reduces the renal and hepatic oxidative stress induced by MTX. Vit C can ameliorate the toxic effect of MTX in liver and kidney tissues of rat.

Effect of an oral anxiolytic medication and heart rate variability on image quality of 64-slice MDCT coronary angiography.

PURPOSE: The aim of the study was to investigate the relationship between image quality in 64-slice multidetector computed tomography (MDCT) and patients' preimaging anxiety status and heart rate variability (HRV), and to evaluate the efficacy of an orally administered anxiolytic medication on HRV and image quality. MATERIALS AND METHODS: Sixty patients [14 women, 46 men; mean age 52.53 ± 10.55 (SD), range 33-78 years] were studied. Anxiety levels were assessed with the State-Trait Anxiety Inventory 60 min before the procedure. The participating patients were randomly assigned to one of the two study groups: a control group (no medication administered for anxiety reduction) and an anxiolytic medication group, with 30 patients in each group. The presence of motion artefacts and image quality for each coronary artery segment were evaluated using a four-point grading system. To estimate HRV, the duration of each heartbeat during MDCT data acquisition was measured in each patient. RESULTS: A moderate correlation was found between HRV during MDCT scanning and the mean image quality for all coronary segments (r=0.47, p<0.01). There was an association between HRV and state anxiety scores in all cases (r=0.370, p<0.01). HRV in the patients who received alprazolam was statistically significantly lower than in controls (p<0.05). The average image quality in patients who used alprazolam was also statistically significantly higher than in controls (p<0.05). CONCLUSIONS: The most important finding in our study is that oral premedication to reduce anxiety is also effective in decreasing HRV and improves image quality. Therefore, we suggest that using alprazolam in addition to a ß-blocker may improve image quality in patients undergoing MDCT coronary angiography (MDCT-CA). Anxiolytic usage may improve image quality by lowering the HRV in selected cases where administration of a ß-blocker is contraindicated. We also suggest that further studies in larger series are required to validate this finding.

Relation between aortic stiffness and left ventricular diastolic function in patients with hypertension, diabetes, or both.

OBJECTIVE: To evaluate aortic function and its relation to left ventricular diastolic function in patients with hypertension, diabetes, or both, without coronary artery disease. METHODS: Study groups were composed of 27 healthy participants and 25 patients with hypertension, 24 with diabetes, and 18 with hypertension and diabetes. Coronary artery disease was excluded in all of the study participants. Aortic strain and distensibility were calculated from the aortic diameters measured by echocardiography and blood pressure obtained by sphygmomanometry. RESULTS: There were significant differences between the control and the patient groups (hypertensive, diabetic, and diabetic-hypertensive) in aortic strain (mean (SD) 18 (8)% v 11 (7)%, 9 (3)%, and 8 (3)%, respectively, p < 0.001) and distensibility (10 (5.1) v 3.1 (1.5), 5.1 (2.8), and 2 (0.9) cm2/dyn/10(3), respectively, p < 0.001). In a multivariate analysis, the parameter most closely related to the deceleration time in the control group was aortic distensibility (standardised beta coefficient -0.50, p = 0.002, overall R2 = 0.25). In the patient group, the parameter most closely related to deceleration time was also aortic distensibility (standardised beta coefficient -0.36, p = 0.009, overall R2 = 0.13). Even though the study group variable was entered in to the multivariate model, aortic distensibility was found to be the parameter most closely related to deceleration time (standardised beta coefficient -0.48, p < 0.001, overall R2 = 0.22). CONCLUSION: Aortic stiffness is increased in patients with hypertension, diabetes, or both even after the exclusion of coronary artery disease. Aortic stiffness and left ventricular diastolic dysfunction are also associated in these patients.

The determinants of systolic pulmonary venous flow reversal by transthoracic pulsed Doppler in mitral regurgitation: its value in determining the severity of regurgitation.

OBJECTIVE: Systolic pulmonary venous flow reversal (SPVFR) has been evaluated in mitral regurgitation (MR) primarily by transoesophageal echocardiography (TEE). There is limited study on the value of SPVFR obtained from transthoracic echocardiography (TTE) for the quantification of MR. In this study, determinants of SPVFR and the accuracy of SPVFR obtained with TTE in determining the severity of MR were investigated. METHODS AND RESULTS: Fifty patients with MR in whom reference quantitative Doppler evaluation was carried out formed the study group. Thirty-nine of them underwent cardiac catheterization. In all patients, SPVFR was evaluated by pulsed Doppler echo placed both at the right and left pulmonary vein in the apical four-chamber view. The SPVFR was present in 26 (52%) patients. Atrial fibrillation, and grade III-IV MR by catheterization were more frequent in patients who had SPVFR. Patients with SPVFR had increased values for regurgitant orifice area, regurgitant volume, regurgitant fraction, and left atrium/left ventricle diameters and volumes compared to patients without SPVFR. After multivariate analysis regurgitant fraction (RF) was the single and most powerful determinant of SPVFR (p<0.001). The SPVFR had high sensitivity, specificity and accuracy for the diagnosis of severe MR (89, 95 and 92%, respectively). CONCLUSION: It was concluded that SPVFR is a useful method for the evaluation of the severity of mitral regurgitation.

Proximal isovelocity surface area (PISA) as a noninvasive method for the estimation of the shunt quantification in perimembranous ventricular septal defects.

This study was designed to assess the reliability of the proximal isovelocity surface area (PISA) method for the estimation of shunt quantification in perimembranous ventricular septal defects (PVSD). The study group was composed of 30 patients (age 11 +/- 7 years, 13 female) with PVSD. The shunt flow (Qp-Qs) and the ratio of the pulmonary flow to the systemic flow (Qp/Qs) were calculated by spectral Doppler and catheterization. The Qp-Qs, the defect area (DA), and the shunt volume (SV) were obtained by the PISA method. The PISA method estimated the DA (cm(2)/m(2)), the SV (cm(3)/m(2)), and the Qp-Qs (L/min/m(2)) to be equal to (2 x pi x R(2) x NL)/(V(max) x Body surface area), DA x TVI(shunt), and to SV x Heart rate, respectively (R is the distance of the maximal PISA from the first aliasing line to the left ventricular side of the defect, NL is the nyquist limit, and V(max) and TVI(shunt) are the peak velocity and time-velocity integral of transdefect Doppler tracing obtained by continuous-wave Doppler). The PISA method (3.4 +/- 1.5 L/min/m(2)) underestimated the Qp-Qs according to spectral Doppler (r = 0.96, P < 0.001; mean difference -0.74 +/- 0.61 L/min/m(2); SEE = 0.11 L/min/m(2), P < 0.001) and catheterization (r = 0.92, P < 0.001; mean difference -0.45 +/- 0.7 L/min/m(2); SEE = 0.13 L/min/m(2), P < 0.001). The correlations between the PISA findings (Qp-Qs, DA, SV) and the catheterization Qp/Qs (r = 0.86, 0.84, and 0.86; P < 0.001, respectively), or between these and the spectral Doppler Qp/Qs (r = 0.80, 0.80, and 0.79; P < 0.001, respectively) were significant. The accuracies of the PISA findings in identifying large defects were high (0.90, 0.93, and 0.90 for cut-off values of Qp-Qs = 3.67 L/min/m(2), DA = 0.44 cm(2)/m(2), and SV = 43 cm(3)/m(2), respectively). As a result, the PISA method can be a simple and reliable alternative to the spectral Doppler method in the identification of large shunts in PVSD.

[The evaluation of the severity of mitral regurgitation using color Doppler echocardiographic methods]. / Renkli Doppler ekokardiyografi yöntemleri ile mitral yetersizligi ciddiyetinin degerlendirilmesi.

OBJECTIVE: This study was planned to assess the vena contracta (VC), flow convergence area (PISA) and jet area (JA) methods in evaluating the severity of mitral regurgitation (MR) and to test the accuracy of a proposed algorithm using these methods. METHODS: Eighty-seven patients with chronic MR were enrolled in the study. VC of < 0.3 cm, maximal MR flow rate calculated by PISA (Qmax) of < 72 cm3/sn and JA of < 4 cm2 were classified as mild MR. VC of > 0.5 cm, Qmax of > 240 cm3/sn and JA of > 8 cm2 were classified as severe MR. Whereas the values between these ranges were called to be moderate MR. The algorithm was planned as follows: In the first step, VC width was measured. If a patient has VC = 0.3-0.5 cm, it was used Qmax in the eccentric jets and JA in the central jets in the second step. The severity of MR were considered as severe, moderate and mild for > 50%, 21-49% and 20% of the regurgitant fraction calculated by the reference method (the quantitative Doppler method depending on aortic and mitral stroke volumes), respectively. RESULTS: The sensitivity of VC was low in differentiating between moderate and severe MR (63%). In eccentric jets, the regurgitant volume calculated by PISA was higher than that of reference method (70 +/- 49 vs. 59 +/- 29 cm3) and the JA was found to be less than that of central jets despite similar regurgitant fraction (6.8 +/- 3.2 vs. 8.5 +/- 3.3 cm2). The algorithm agreed well with the reference method and it was better than those of each tree methods (Cappa coefficients 0.89 vs. 0.65, 0.63 and 0.45 for VC, Qmax and JA; respectively). The accuracies of the algorithm in discriminating between mild and moderate MR or severe and non-severe MR were high (98% and 95%, respectively). CONCLUSIONS: The severity of MR can be determined accurately and simply by using VC, PISA and JA methods together.

[Value of tissue Doppler imaging in the determination of the right ventricular systolic function]. / Sag ventrikül sistolik fonksiyonunun belirlenmesinde doku Doppler yönteminin degeri.

OBJECTIVE: Since there is a difficulty in the assessment of right ventricular systolic function by 2D echocardiography, a noninvasive, practical and, cost effective method is desirable. Tissue Doppler technique enables to visualize systolic and diastolic velocities of the tissue through sample volume replacement. In this study, we aimed to evaluate the relationship between tricuspid annular tissue Doppler velocities and right ventricular systolic functions. METHODS: For this purpose, tricuspid annular systolic (S), early diastolic (E) and, late diastolic (A) velocities were obtained from 38 patients (23 with dilated cardiomyopathy, 15 with mitral stenosis, all of them in sinus rhythm) and 15 healthy control subjects by placing the pulsed wave sample volume at the junction of right ventricular free wall and tricuspid annulus. The time velocity integral (TVI) of S, peak velocity of S and isovolumic contraction time (IVCT) were compared with right ventricular ejection fraction (RVEF) determined by 2D echocardiographic hemi-elliptic shell model, peak velocity of tricuspid regurgitation and dP/dt calculated from the spectral trace of this regurgitation. RESULTS: A significant correlation was determined between RVEF and peak S velocity, S TVI and IVCT (r: 0.76, p < 0.001, r: 0.82, p < 0.0001 and r: -0.85, p < 0.0001 respectively). The peak S velocity < 12 cm/sec, S TVI < 2 cm and IVCT > 75 msec yielded 76%, 84%, 92% sensitivity and 84%, 84%, 80% specificity for predicting the patients with right ventricular ejection fraction < 40%, respectively. A significant and powerful correlation was determined between the peak S velocities and dP/dt in 19 patients whose tricuspid regurgitation could be clearly recorded (r: 0.88, p < 0.0001). CONCLUSIONS: The analysis of tricuspid annular velocities obtained by tissue Doppler technique is a practical method of the assessment of right ventricular systolic functions.

[Evaluation of dynamic left ventricular outflow tract obstruction by dobutamine stress echocardiography]. / Dinamik sol ventrikül çikis yolu obstrüksiyonlarinin dobutamin stres ekokardiyografi ile degerlendirilmesi.

OBJECTIVE: This study was planned to evaluate the dynamic left ventricular outflow tract (LVOT) obstruction by using dobutamine stress echocardiography (DSE) in patients with asymmetric septal hypertrophy and/or septal bulging, who have no signs of LVOT gradient detected by conventional echocardiography, with symptoms mimicking hypertrophic obstructive cardiomyopathy (HOCM). METHODS: In sixty-one consecutive patients referred to our echocardiography laboratory with HOCM pre-diagnosis, exercise dyspnea and limitation of exercise capacity were evaluated. DSE was performed in 31 patients who fulfilled the inclusion criteria. Patients were divided into two groups according to the degree of dynamic gradient increase above baseline values during stress-test (Group 1 < 30 mmHg, Group 2 > 30 mmHg). Left ventricular diameters, septum and posterior wall thicknesses, ejection fraction, LVOT and aortic root diameters, presence of septal bulging and systolic anterior motion (SAM) and degree of septal angulation were sought. RESULTS: There were no significant differences between groups by means of LV diameters, septum and posterior wall thicknesses, EF, LVOT and aortic root diameters, presence of septal bulging (p > 0.05); whereas there were significant differences in SAM and degree of septal angulation (p < 0.05 and p < 0.0001, respectively). Systolic anterior motion (r = 0.61, p < 0.0001) and degree of septal angulation (r = -0.71, p < 0.001) correlated significantly with the dynamic gradient increase. CONCLUSION: Presence of SAM and degree of septal angulation obtained by DSE are reliable parameters to determine dynamic LVOT obstruction in patients who have asymmetric septal hypertrophy and septal bulging with no gradient on LVOT by conventional echocardiography.

[Quantitative ultrasonic myocardial texture analysis of the diabetic heart]. / Diyabet kalbinin kantitatif ultrasonik miyokard dokusu analizi.

OBJECTIVE: Contraction and relaxation of the heart cause decrease and increase in myocardial video intensity (MVI) recorded from echocardiographic images, respectively. The present study was planned to compare this physiological cyclic variations of MVI in patients with type 1 diabetes mellitus and healthy subjects. METHODS: For this purpose, standard echocardiographic examination was performed to 18 young patients (age 23.2+6.4; range: 15-37 years) with insulin dependent type 1 diabetes mellitus (diabetes duration: 7.8+5.6; range: 1-17 years) and 14 age and sex matched controls. In all subjects, end-diastolic and end-systolic 2D echocardiographic images of 3 consecutive beats that had been recorded on videotapes were digitized. The quantitative analysis of digitized imaging was performed with the help of a calibrated digitization system in order to calculate the septum and the posterior wall textural parameters. The cyclic variation index (CVI) of the mean gray level (MGL) was calculated according the formula: (MGL dias- MGL diast x 100. RESULTS: Among the groups, left ventricular diastolic dimension-index, fractional shortening, E/A ratio, and isovolumic relaxation time showed no statistically significant differences, while septum and (8.3+1.1 vs. 7.3+0.9 mm; p=0.016) and posterior wall thickness (8+0.6 vs. 6.8+1.1mm; p=0.004) and E-deceleration time (167+23 vs. 140=19 msec.; p=0.003) were significantly higher in diabetics. The diabetic patients showed significantly lower CVI both for septum (18.2+11.5% vs. 39.3+11.5%; p=0.0001) and posterior wall (16.4+16% vs. 40.5+9.2%; p=0.0001), respectively. CONCLUSIONS: Altered videoensitometric parameters possibly represent a preclinical alteration, conceivably related to the myocardial collagen content increase, which does not necessarily indicate an actual disease but may be considered an early marker of the histopathologic findings of diabetic cardiomyopathy.

Prediction of viability by pulsed-wave Doppler tissue sampling of asynergic myocardium during low-dose dobutamine challenge.

Dobutamine stress echocardiography is widely used to predict reversible left ventricular dysfunction, but evaluation with this method is subjective. Pulsed-wave tissue Doppler imaging is a new technique that allows to obtain quantitative data on wall motion velocities of different myocardial segments through sample-volume placement. Therefore, this tool in combination with DSE may be suitable for identifying viability in asynergic myocardium. To evaluate this, in 40 patients (mean age 57+/-9) with resting dyssynergy (akinesis in 52, hypokinesis in 30) baseline wall motion scores and tissue Doppler variables were collected before and after 5 min infusion of 10 microg/kg per min dobutamine. Forty-six of 82 segments were classified as viable (a reduction in segmental score of at least one grade) according to follow-up echocardiography that was performed 4 weeks after revascularization. While myocardial S velocity percent increase in viable segments was 45+/-10, the increase was 25+/-12 in necrotic segments (n=36) during 10 microg dobutamine infusion (P=0.0001). Assuming 35% as a cut-off for viability the increase in S velocities by DSE yielded an 89% sensitivity and 86% specificity for predicting post-revascularization functional recovery. In conclusion, pulsed-wave tissue Doppler imaging of asynergic myocardium during dobutamine stress echocardiography can identify the viability quantitatively.

Usefulness of pulse-wave Doppler tissue sampling and dobutamine stress echocardiography for identification of false positive inferior wall defects in SPECT.

False positive inferior wall perfusion defects restrict the accuracy of SPECT in diagnosis of coronary artery disease (CAD). Pulse-Wave Tissue Doppler (PWTD) has been recently proposed to assess regional wall motion velocities. The objectives of this study were to evaluate the presence of CAD by using PWTD during dobutamine stress echocardiography (DSE) in patients with an inferior perfusion defect detected by SPECT and compare PWTD parameters of normal cases with patients who had inferior perfusion defect and CAD. Sixty-five patients (mean age 58 +/- 8 years, 30 men) with a normal LV systolic function at rest according to echocardiographic evaluation with an inferior ischemia determined by SPECT and a control group (CG) of 34 normal cases (mean age 56 +/- 7 years, 16 men) were included in this study. All patients underwent a standard DSE (up to 40 microg / kg / min with additional atropine during sub-maximum heart rate responses). Pulse-wave Doppler tissue sampling of inferior wall was performed in the apical 2-chamber view at rest and stress. The coronary angiography was performed within 24 hours. The results were evaluated for the prediction of significant right coronary artery (RCA) and / or left circumflex coronary artery (CX) with narrowing (> or = 50% diameter stenosis, assessed by quantitative coronary angiography). It was observed that the peak stress mean E / A ratio was lower in patients with CAD when compared to patients without CAD (0.78 +/- 0.2 versus 1.29 +/- 0.11 p < 0.0001). Also the peak stress E / A ratio of normal cases was significantly higher than patients who had CAD (1.19 +/- 0.3 versus 0.78 +/- 0.2 p < 0.0001). When the cut off point for the E / A ratio was determined as 1, the sensitivity and specificity of dobutamine stress PWTD E / A were 89% and 86 %, respectively. The peak stress E / A ratio was higher than 1 in all patients with a false positive perfusion defect. Systolic S velocity increase during DSE was significantly lower in patients with CAD (54 % +/- 17 versus 99 % +/- 24 p = 0.01). The analysis of S velocity increase yielded 81% sensitivity and 76 % specificity for prediction of CAD when a 70 % increase was accepted as a cut-off value. Pulse-wave Doppler tissue sampling during DSE may help to identify false positive inferior wall defects detected by SPECT.