Long-term protective effects of the angiotensin receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress, and myocardial dysfunction.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9006-9006
Author(s):  
Giovanni Mantovani ◽  
Mariele Dessi' ◽  
Alessandra Piras ◽  
Clelia Madeddu ◽  
Laura Orgiano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Inflammation ◽  
Systolic Function ◽  
Myocardial Dysfunction ◽  
Renin Angiotensin System ◽  
Serum Levels ◽  
Tissue Doppler ◽  
Doppler Imaging ◽  
Protective Effects ◽  
Strain And Strain Rate

9006 Background: Chronic inflammation, oxidative stress and renin-angiotensin system (RAS) play a significant role in chemotherapy-induced cardiotoxicity (CTX). Telmisartan (TEL), an antagonist of the angiotensin II type-1 receptor, reduces anthracycline (ANT)-induced CTX. Methods: A phase II placebo (PLA)-controlled randomized trial was carried out to assess the role of TEL in the prevention of cardiac subclinical damage induced by epirubicin (EPI). Forty-nine patients (mean age ± SD, 53.0±8 years), cardiovascular disease-free with cancer at different sites and eligible for EPI-based treatment, were randomized to one of two arms: TEL n=25; PLA n=24. A conventional echocardiography equipped with Tissue Doppler imaging, strain and strain rate (SR) was performed, and serum levels of proinflammatory cytokines, IL-6 and TNF-α, and oxidative stress parameters, reactive oxygen species (ROS) and glutathione peroxidase were assessed. All assessments were carried out at baseline, after every 100 mg/m2 EPI dose and at 6, 12 and 18-month follow-up (FU). Results: A significant reduction in the SR peak in both arms was observed at t2 (cumulative dose of 200 mg/m2 EPI) in comparison to t0. Conversely, at t3, t4 (300, 400 mg/m2 EPI), 6, 12 and 18-month FU, the SR increased reaching the normal range only in TEL arm, while in PLA arm SR remained significantly lower as compared to t0. The differences between SR changes in PLA and TEL arms were significant from 300 mg/m2 EPI (t3) up to 18 month-FU. IL-6 increased significantly in PLA arm at t2 compared to t0, but remained unchanged in the TEL arm. ROS levels also increased significantly at t2 vs. baseline in PLA arm, while remained unchanged in TEL arm. The mean change in ROS and IL-6 at t2 was significantly different between the two arms. At 3, 6, 12 and 18 month-FU, ROS and IL-6 decreased in comparison to t2 in PLA arm, while remained low in TEL arm. Conclusions: Our results suggest that TEL is able to reverse acute EPI-induced myocardial dysfunction and maintain a normal systolic function up to 18 month-FU. These effects are likely due to two different mechanisms, RAS blockade and prevention of chronic inflammation/oxidative stress.

Cardioprotective effect of telmisartan in cancer patients treated with epirubicin

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20671-e20671
Author(s):  
G. Mantovani ◽  
G. Mercuro ◽  
M. Dessì ◽  
C. Madeddu ◽  
R. Serpe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cancer Patients ◽  
Renin Angiotensin System ◽  
Myocardial Damage ◽  
Tissue Doppler ◽  
Doppler Imaging ◽  
Controlled Study ◽  
Type I ◽  
Oxidative Stress Markers ◽  
Stress Markers

e20671 Background: We previously showed on 31 cancer patients (pts) that early cardiac abnormalities occurred at epirubicin (EPI) doses of 200 mg/m2 and persisted throughout subsequent EPI doses and even up to 18 months. Early contractility impairment, i.e. Strain rate (SR) reduction was detected by tissue doppler imaging (TDI) associated with high levels of inflammatory/oxidative stress markers. Renin-angiotensin system activation has been suggested to play an important role in the pathogenesis of Anthracycline-induced cardiotoxicity. Methods: A phase II placebo-controlled study was designed to investigate the possible role of telmisartan (an antagonist of angiotensine II type I receptor) in preventing both early preclinical and late myocardial damage induced by EPI. The correlation with changes of biochemical/inflammatory markers was also assessed. Planned sample size was 100 pts (50 pts per arm). Inclusion criteria: 18–70 y, histologically confirmed cancer, previously untreated and candidates for an EPI-based regimen; LVEF ≥55%; ECOG PS 0–2, no history of cardiac disease and previous mediastinal irradiation. Eligible pts were randomized to receive telmisartan 40 mg (1 tablet)/day or placebo starting 1 week before EPI until 6 months after the end of EPI administration. TDI as well as inflammatory/oxidative stress markers were assessed at baseline, 24 hours and 7 days at EPI doses of 100, 200, 300, and 400 mg/m2. Results: At December 2008 we enrolled 27 pts (M/F: 7/20, mean±SD age 58±14 years): 14 telmisartan and 13 placebo. 15 pts completed EPI treatment (8 telmisartan and 7 placebo). A significant reduction of SR peak was observed at 200mg/m2 of EPI in the placebo arm. Viceversa no significant TDI changes occurred in the treatment arm. Proinflammatory cytokines did not change in both arms whilst reactive oxygen species increased significantly in the placebo arm. Conclusions: The study is in progress. No significant financial relationships to disclose.

scholarly journals Overexpression of Transcripts Coding for Renin-b but Not for Renin-a Reduce Oxidative Stress and Increase Cardiomyoblast Survival under Starvation Conditions

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1204
Author(s):  
Heike Wanka ◽  
Philipp Lutze ◽  
Alexander Albers ◽  
Janine Golchert ◽  
Doreen Staar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
B Cells ◽  
Apoptotic Cell ◽  
Renin Angiotensin System ◽  
Glucose Deprivation ◽  
Protective Effects ◽  
Glucose Depletion ◽  
A Cells ◽  
Apoptosis And Necrosis

A stimulated renin-angiotensin system is known to promote oxidative stress, apoptosis, necrosis and fibrosis. Renin transcripts (renin-b; renin-c) encoding a cytosolic renin isoform have been discovered that may in contrast to the commonly known secretory renin (renin-a) exert protective effects Here, we analyzed the effect of renin-a and renin-b overexpression in H9c2 cardiomyoblasts on apoptosis and necrosis as well as on potential mechanisms involved in cell death processes. To mimic ischemic conditions, cells were exposed to glucose starvation, anoxia or combined oxygen–glucose deprivation (OGD) for 24 h. Under OGD, control cells exhibited markedly increased necrotic and apoptotic cell death accompanied by enhanced ROS accumulation, loss of mitochondrial membrane potential and decreased ATP levels. The effects of OGD on necrosis were exaggerated in renin-a cells, but markedly diminished in renin-b cells. However, with respect to apoptosis, the effects of OGD were almost completely abolished in renin-b cells but interestingly also moderately diminished in renin-a cells. Under glucose depletion we found opposing responses between renin-a and renin-b cells; while the rate of necrosis and apoptosis was aggravated in renin-a cells, it was attenuated in renin-b cells. Based on our results, strategies targeting the regulation of cytosolic renin-b as well as the identification of pathways involved in the protective effects of renin-b may be helpful to improve the treatment of ischemia-relevant diseases.

Trends in pediatric imaging: ultrasound

2013 ◽  
Vol 54 (9) ◽  
pp. 1096-1105 ◽  
Author(s):  
Ansgar Berg ◽  
Gottfried Greve
Keyword(s):  
Heart Diseases ◽  
Three Dimensional ◽  
Cost Effective ◽  
Clinical Work ◽  
Ventricular Volume ◽  
Tissue Doppler ◽  
Doppler Imaging ◽  
Strain And Strain Rate ◽  
2D Echocardiography ◽  
Systolic And Diastolic Function

For the last three decades, two-dimensional (2D) echocardiography and Doppler echocardiography have been the primary imaging modalities for the diagnosis and management of heart disease in infants, children, and adolescents. These methods are non-invasive, highly sensitive, and cost-effective, and widely available, making them very useful in clinical work. During this period, the anatomic and hemodynamic abnormalities associated with different congenital and acquired pediatric heart diseases have been well outlined by echocardiography. Recent advances in computer technology, signal processing, and transducer design have allowed the capabilities of pediatric echocardiography to be expanded beyond qualitative 2D imaging and blood flow Doppler analysis. New modalities such as three-dimensional echocardiography, tissue Doppler imaging and speckle tracking echocardiography have been used to evaluate parameters such as ventricular volume, myocardial velocity, regional strain, and strain rate, providing new insight into cardiovascular morphology and ventricular systolic and diastolic function. Accordingly, a comprehensive and sophisticated quantification of ventricular function is now part of most echocardiography protocols. Use of measurements adjusted for body size and age is common practice today. These developments have further strengthened the position of echocardiography in pediatric cardiology.

Protective Effects of Ginsenosides on 17α-Ethynyelstradiol-Induced Intrahepatic Cholestasis via Anti-Oxidative and Anti-Inflammatory Mechanisms in Rats

2017 ◽  
Vol 45 (08) ◽  
pp. 1613-1629 ◽  
Author(s):  
Yan-Jiao Xu ◽  
Zao-Qin Yu ◽  
Cheng-Liang Zhang ◽  
Xi-Ping Li ◽  
Cheng-Yang Feng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alkaline Phosphatase ◽  
Superoxide Dismutase ◽  
Protein Expression ◽  
Intrahepatic Cholestasis ◽  
Serum Levels ◽  
Total Bile Acid ◽  
Protective Effects ◽  
Sod Activity ◽  
Mda Content

The present study was designed to assess the effects and potential mechanisms of ginsenosides on 17[Formula: see text]-ethynyelstradiol (EE)-induced intrahepatic cholestasis (IC). Ginsenoside at doses of 30, 100, 300[Formula: see text]mg/kg body weight was intragastrically (i.g.) given to rats for 5 days to examine the effect on EE-induced IC. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bile acid (TBA) were measured. Hepatic malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were determined. Protein expression of proinflammatory cytokines TNF-[Formula: see text], IL-6 and IL-1[Formula: see text] was analyzed by immunohistochemistry and Western blot. Results indicated that ginsenosides remarkably prevented EE-induced increase in the serum levels of AST, ALT, ALP and TBA. Moreover, the elevation of hepatic MDA content induced by EE was significantly reduced, while hepatic SOD activities were significantly increased when treated with ginsenosides. Histopathology of the liver tissue showed that pathological injuries were relieved after treatment with ginsenosides. In addition, treatment with ginsenosides could significantly downregulate the protein expression of TNF-[Formula: see text], IL-6 and IL-1[Formula: see text] compared with EE group. These findings indicate that ginsenosides exert the hepatoprotective effect on EE-induced intrahepatic cholestasis in rats, and this protection might be attributed to the attenuation of oxidative stress and inflammation.

scholarly journals THE DIAGNOSTIC AND PROGNOSTIC VALUE OF RIGHT VENTRICLE SYSTOLIC AND DIASTOLIC FUNCTION IN INFERIOR MYOCARDIAL INFARCTION

Biomedika ◽  
2018 ◽  
Vol 10 (1) ◽  
Author(s):  
Niniek Purwaningtyas
Keyword(s):  
Myocardial Infarction ◽  
Diastolic Function ◽  
Sensitivity And Specificity ◽  
Systolic Function ◽  
Tissue Doppler ◽  
Doppler Imaging ◽  
Inferior Myocardial Infarction ◽  
St Segment Elevation ◽  
St Segment ◽  
Systolic And Diastolic Function

Right ventricular (RV) involvement increases mortality and morbidity in inferior myocardial infarction (MI). There are sparse data on the usefulness of pulsed tissue Doppler imaging (TDI) in the diagnosis of RV dysfunction in ST segment elevation MI (STEMI). This study evaluate the diagnostic and prognostic significance of RV systolic and diastolic function compared to classical electrocardiographic RVMI diagnostic criteria in this group of patients. Consecutive patients with first, acute, inferior STEMI were prospectively assessed. The RVMI was defined as an ST-segment elevation ≥ 0.1 mV in lead V4R. Echocardiography with TDI was performed within24 h of the onset of symptoms. Out of 31 patients (mean age 56.39 ± 9.02 years), RVMI was found in 18 (37%). Multivariate analysis showed that two variables—RV systolic and diastolic function, were independent predictors of in-hospital prognosis. Sensitivity and specificity the RV systolic function were 94,4% and 69,2%, respectively. While RV diastolic function were 44% and 76,9%, respectively. RV systolic function predict ECG diagnosis of RVMI with relatively high sensitivity and specificity. RV diastolic function predict ECG diagnosis of RVMI with relatively low sensitivity but with high specificity.Keywords: tissue Doppler imaging, RV myocardial infarction, inferior myocardial infarction

scholarly journals Reduced myocardial reserve in cirrhotic patients: an evaluation by dobutamine stress speckle tracking and tissue Doppler imaging (TDI) echocardiography

2019 ◽  
Vol 11 (2) ◽  
pp. 127-131 ◽  
Author(s):  
Mahmood Zamirian ◽  
Forough Afsharizadeh ◽  
Alireza Moaref ◽  
Firoozeh Abtahi ◽  
Fatemeh Amirmoezi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Strain Rate ◽  
Speckle Tracking ◽  
Systolic Function ◽  
Peak Stress ◽  
Tissue Doppler ◽  
Doppler Imaging ◽  
Control Group ◽  
Basal Segment ◽  
Cirrhotic Patients

Introduction: Despite the normal systolic function at rest, cirrhotic patients often suffer from volume overload and symptoms of heart failure as they face stressful situations. This study investigated the myocardial reserve in cirrhotic patients at resting condition and peak stress by dobutamine speckle tracking echocardiography (STE) and tissue Doppler imaging (TDI). Methods: Twenty cirrhotic patients and 10 normal individuals aged 30-50 were selected randomly. For all of the participants, complete echocardiographic study of 2D, STE and TDI was done at rest and peak stress status with dobutamine. The following parameters were assessed: ejection fraction (EF), global longitudinal LV strain (GLS), strain rate in the septal basal segment and lateral wall and E’ in the septal basal segment by color-coded method. Results: At baseline, EF was higher than 55% in both groups. GLS was higher (-22.6±2.4%) in the case group than the control group (-19.2±1.9%) at resting condition. After stress, it showed a greater increase (-22.5±1.7%) in the controls compared to cirrhotic patients (-22.6±3.3%; mean difference = 2.6 ± 2.03, P = 0.02). In cirrhotic patients, the average strain rate in the basal septal segment decreased after stress (-1.2 ± 0.3/s to-1.1 ± 0.3/s), but it increased in the control group (-1.1 ± 0.2/s to -1.8 ± 0.2/s). Conclusion: Despite the presence of normal resting systolic function in cirrhotic patients, there was insufficient increase or even a decrease in myocardial function with stress; this may indicate the absence of sufficient myocardial reserve in cirrhotic patients. These findings would help to explain the reason for occurrence of heart failure or hemodynamic changes in cirrhotic patients.

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