Cytoprotective effects of spirulina extract against doxorubicin‐induced cardiotoxicity: Biochemical evidences and translational perspectives in cardio-oncology.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15042-e15042
Author(s):  
Nicola Maurea ◽  
Vincenzo Quagliariello ◽  
Andrea Paccone ◽  
Michelino De Laurentiis ◽  
Simona Buccolo ◽  
...  
Keyword(s):  
Cell Viability ◽  
Transcriptional Activation ◽  
Calcium Content ◽  
Left Ventricular ◽  
Lipid Lowering ◽  
Left Ventricular Ejection ◽  
Myocardial Inflammation ◽  
Blue Green Algae ◽  
Fetal Cardiomyocytes ◽  
Cardiac Strain

e15042 Background: Spirulina, a blue-green algae used in the daily diet of natives of Africa and America, has antioxidant, anticancer, antiviral, hepatoprotective, immune enhancing and lipid-lowering effects. Considering that doxorubicin-induced cardiotoxicity involves myocardial inflammation, ferroptosis and overexpression of several cytokines involved in cell dead and apoptosis, the use of spirulina during exposure to doxorubicin could be an intriguing method to reduces myocardial injuries in cancer patients undergoing treatment with anthracyclines. Methods: Human fetal cardiomyocytes (HFC cell line) were exposed to doxorubicin (from 10 to 500 nM), alone or in combination with spirulina extract (from 10 to 100 µg/ml) for 24 and 48h. After the incubation period, we performed the following tests: determination of cell viability, through analysis of mitochondrial dehydrogenase activity, study of lipid peroxidation (quantifying cellular Malondialdehyde and 4-hydroxynonenal), intracellular Ca2+ homeostasis. Moreover, pro-inflammatory studied were also performed (activation of NLRP3 inflammasome; expression of TLR4/MyD88; mTORC1 Fox01/3a; transcriptional activation of p65/NF-κB and secretion of cytokines involved in cardiotoxicity (Interleukins 1β, 8, 6). Results: Spirulina extract, co-incubated with doxorubicin exerts cardioprotective effects, enhancing cell viability of 20-36.7 % compared to untreated cells (p<0,01 for all); spirulina extract reduced significantly the cardiotoxicity through MyD88/NF-KB/cytokines axis and mTORC1 Fox01/3α mediated mechanisms and reduces oxidative damages of doxorubicin resulting in lower intracellular calcium content. Conclusions: For the first time, it was demonstrated that spirulina extract exert anti-inflammatory and cytoprotective properties in myocardial cells exposed to growing concentration of doxorubicin leading to preclinical studies in mice analyzing any effects on cardiac strain and left ventricular ejection function.

scholarly journals Serum autotaxin level predicts future cardiac events in patients with dilated cardiomyopathy

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
T Araki ◽  
T Okumura ◽  
T Mizutani ◽  
Y Kimura ◽  
S Kazama ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Dilated Cardiomyopathy ◽  
Volume Fraction ◽  
Left Ventricular ◽  
Cox Proportional Hazards ◽  
Left Ventricular Ejection ◽  
Myocardial Inflammation ◽  
Prognostic Impact ◽  
Cardiac Events ◽  
Ventricular Ejection Fraction

Abstract Background Autotaxin (ATX) has been reported to promote myocardial inflammation and subsequent cardiac remodeling through lysophosphatidic acid (LPA) production. However, the prognostic impact of ATX has not been clarified in dilated cardiomyopathy (DCM). Purpose We aimed to investigate the prognostic impact of ATX in patients with DCM. Methods We enrolled 104 DCM patients (49.8 years, 76 males). The subjects underwent blood sampling, echocardiography, cardiac catheterization, and endomyocardial biopsy. Gender differences in serum ATX levels have been reported, thus we divided the subjects into two groups using median serum ATX levels for men and women: High-ATX group and Low-ATX group. All patients were followed up by expert cardiologists. The cardiac event was defined as a composite of cardiac death and hospitalization for worsening heart failure. Results Eighty-nine percent of the subjects were classified as New York Heart Association functional class I or II. Female patients had higher serum ATX levels than male patients, with median values of 257.0 ng/mL and 203.5 ng/mL, respectively (Figure A). The average left ventricular ejection fraction and brain natriuretic peptide levels were 30.6% and 122.5 pg/mL. In survival analysis, cumulative event-free probability was significantly lower in High ATX group (p=0.007, Figure B). In Cox proportional hazards analysis, High-ATX was one of the independent predictors of composite cardiac events (Hazards Ratio, 2.575; p=0.043). On the other hand, high sensitive C-reactive protein and collagen volume fraction in myocardial samples were not significant predictors. Conclusion High serum ATX level was associated with poor prognosis in patients with DCM. FUNDunding Acknowledgement Type of funding sources: None. Gender difference in autotaxin levels Survival analysis of cardiac events

Abstract 1616: Intermediate Dose of Pentaglobin Eradicates Effectively Inflammation in Parvo B19 and Adenovirus Positive Myocarditis

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Bernhard Maisch ◽  
Hendrik Haake ◽  
Nadine Schlotmann ◽  
Sabine Pankuweit
Keyword(s):  
Exercise Capacity ◽  
Nyha Class ◽  
Left Ventricular ◽  
Volume Index ◽  
Left Ventricular Ejection ◽  
Myocardial Inflammation ◽  
Ventricular Ejection Fraction ◽  
Nyha Classification ◽  
Before And After ◽  
Intermediate Dose

152 consecutive patients with myocarditis according to the quantitative World Heart Federation Criteria (> 14 infiltrating cells/mm 2 by endomyocardial biopsy(EMB)) were analysed for cardiotropic agents. In 90 pts parvoviruses B19 (59,5%) and in 36 pts adenoviruses (23,8%) were assessd by PCR as causative viral pathogens. All virus positive patients were treated with 10 g/day Pentaglobin® i. v.(enriched IgG, IgA and IgM preparation, Biotest) at day 1 and 3. After six months all patients were reevalutated clinically, 73 patients (48%) in addition by EMB. Methods: We compared the following parameters before and after therapy: left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), shortening fraction (SF) by transthoracic echocardiography and LVEF or the left ventricular end-diastolic volume index (LVEDVI) using angiography. For exercise capacity we evaluated exercise ECG by treadmill test and clinical parameters according to the NYHA classification, before and after therapy. Results: After Pentaglobin therapy, all patients demonstrated a significant clinical improvement of the NYHA class, of exercise capacity and of LVEF (from 54,4 to 60,0%, p<0,005) independent from the respective virus. In 52 of 73 (71%) rebiopsied pts inflammation had resolved. In 17 of the 19 rebiopsied patients (90%) with a positive PCR for ADV before therapy no more virus DNA was recovered after treatment, inflammation had resolved completely. In Parvo B 19 myocarditis inflammation had resolved in 31 of the 44 pts (70%), whereas Parvo B19 DNA was eradicated in only in 18 out of 44 pts(40%). In patients in whom both virus and inflammation were eliminated enddiastolic LV dimension decreased and EF increased significantly (p<0,001). Conclusion: Treatment with an intermediate dose of Pentaglobin is highly effective in resolving myocardial inflammation independent of the underlying viral etiology, but it eradicates adenoviral much better than Parvo B19 infection.

scholarly journals A cardiovascular magnetic resonance imaging-based pilot study to assess coronary microvascular disease in COVID-19 patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stefanos Drakos ◽  
Grigorios Chatzantonis ◽  
Michael Bietenbeck ◽  
Georg Evers ◽  
Arik Bernard Schulze ◽  
...  
Keyword(s):  
Cardiovascular Magnetic Resonance ◽  
Magnetic Resonance ◽  
Myocardial Perfusion Reserve ◽  
Microvascular Disease ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Myocardial Inflammation ◽  
Contrast Imaging ◽  
Flow Measurements ◽  
Ventricular Ejection Fraction

AbstractCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and is primarily characterised by a respiratory disease. However, SARS-CoV-2 can directly infect vascular endothelium and subsequently cause vascular inflammation, atherosclerotic plaque instability and thereby result in both endothelial dysfunction and myocardial inflammation/infarction. Interestingly, up to 50% of patients suffer from persistent exercise dyspnoea and a post-viral fatigue syndrome (PVFS) after having overcome an acute COVID-19 infection. In the present study, we assessed the presence of coronary microvascular disease (CMD) by cardiovascular magnetic resonance (CMR) in post-COVID-19 patients still suffering from exercise dyspnoea and PVFS. N = 22 patients who recently recovered from COVID-19, N = 16 patients with classic hypertrophic cardiomyopathy (HCM) and N = 17 healthy control patients without relevant cardiac disease underwent dedicated vasodilator-stress CMR studies on a 1.5-T MR scanner. The CMR protocol comprised cine and late-gadolinium-enhancement (LGE) imaging as well as velocity-encoded (VENC) phase-contrast imaging of the coronary sinus flow (CSF) at rest and during pharmacological stress (maximal vasodilation induced by 400 µg IV regadenoson). Using CSF measurements at rest and during stress, global myocardial perfusion reserve (MPR) was calculated. There was no difference in left ventricular ejection-fraction (LV-EF) between COVID-19 patients and controls (60% [57–63%] vs. 63% [60–66%], p = NS). There were only N = 4 COVID-19 patients (18%) showing a non-ischemic pattern of LGE. VENC-based flow measurements showed that CSF at rest was higher in COVID-19 patients compared to controls (1.78 ml/min [1.19–2.23 ml/min] vs. 1.14 ml/min [0.91–1.32 ml/min], p = 0.048). In contrast, CSF during stress was lower in COVID-19 patients compared to controls (3.33 ml/min [2.76–4.20 ml/min] vs. 5.32 ml/min [3.66–5.52 ml/min], p = 0.05). A significantly reduced MPR was calculated in COVID-19 patients compared to healthy controls (2.73 [2.10–4.15–11] vs. 4.82 [3.70–6.68], p = 0.005). No significant differences regarding MPR were detected between COVID-19 patients and HCM patients. In post-COVID-19 patients with persistent exertional dyspnoea and PVFS, a significantly reduced MPR suggestive of CMD—similar to HCM patients—was observed in the present study. A reduction in MPR can be caused by preceding SARS-CoV-2-associated direct as well as secondary triggered mechanisms leading to diffuse CMD, and may explain ongoing symptoms of exercise dyspnoea and PVFS in some patients after COVID-19 infection.

scholarly journals Cardiac strains as a tool for optimization of cardiac resynchronization therapy in non-responders: a pilot study

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 945-952
Author(s):  
David Šipula ◽  
Milan Kozák ◽  
Jaroslav Šipula ◽  
Miroslav Homza ◽  
Jiří Plášek
Keyword(s):  
Heart Failure ◽  
Cardiac Resynchronization Therapy ◽  
Speckle Tracking ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Left Ventricular Ejection ◽  
Resynchronization Therapy ◽  
Ventricular Ejection Fraction ◽  
Cardiac Strain ◽  
Maximum Improvement

AbstractBackgroundApproximately 30% of patients do not respond to implantation of Cardiac Resynchronization Therapy – Defibrillators (CRT-D). The aim of this study was to investigate the potential for cardiac strain speckle tracking to optimize the performance of CRT-D in non-responding patients.Methods30 patients not responding to Cardiac Resynchronization Therapy-Defibrillators after 3 months were randomly divided into control and intervention groups. Atrioventricular interval was adjusted so that E and A waves did not overlap, the interventricular interval was subsequently optimized to yield maximum improvement of the sum of longitudinal+radial+circumferential strains. The left ventricular ejection fraction (LVEF) and NYHA improvement 3 months after optimization were evaluated and use of other strain combinations assessed.ResultsA significant correlation between the (combined) strain change and LVEF improvement was detected (p<0.01). 75% of patients with non-ischemic etiology of heart failure who did not respond to the original CRT-D reacted favorably with significant LVEF and NYHA improvement. The area strain was the best predictor of LVEF/NYHA improvement in those patients. No significant improvement was recorded in patients with ischemic etiology.ConclusionsAV and VV optimization based on speckle tracking is a very promising method potentially leading to a significant improvement of the outcome of CRT-D, especially in patients with non-ischemic etiology of heart failure.

Evidence for lack of myocardial injury in children with acute rheumatic carditis

2002 ◽  
Vol 12 (6) ◽  
pp. 519-523 ◽  
Author(s):  
Richard V. Williams ◽  
L. LuAnn Minich ◽  
Robert E. Shaddy ◽  
L. George Veasy ◽  
Lloyd Y. Tani
Keyword(s):  
Mitral Regurgitation ◽  
Cardiac Troponin ◽  
Myocardial Injury ◽  
Troponin I ◽  
Left Ventricular ◽  
Cardiac Troponin I ◽  
Left Ventricular Ejection ◽  
Myocardial Inflammation ◽  
Rheumatic Carditis ◽  
Ventricular Ejection Fraction

Despite pathologic evidence of myocardial inflammation, the significance of myocarditis in children with acute rheumatic carditis remains controversial. Elevations in cardiac troponin I have been demonstrated in other forms of myocarditis. The purpose of our study was to determine if levels of cardiac troponin I are elevated, suggesting myocardial injury, in patients with acute rheumatic carditis. We identified all those patients with acute rheumatic fever, presenting between July 1998 and December 2000, who had clinical evidence of carditis, such as a new murmur of mitral or aortic regurgitation, and who had an echocardiogram, measurements of levels of cardiac troponin I, erythrocyte sedimentation rate, and/or C-reactive protein performed at the time of presentation. Their charts were reviewed for demographic and clinical data. Echocardiograms were reviewed for severity of aortic and mitral regurgitation, and measurements made of left ventricular ejection fraction, fractional shortening, and end-diastolic dimension. We found 16 patients with acute rheumatic carditis, ranging in age from 2.0 to 16.1 years, with just over one-third having symptoms of congestive heart failure. All patients had evidence of acute inflammation. There was a significant relationship between symptoms and severity of mitral regurgitation. No patient had elevated levels of cardiac troponin I level. The fact that levels of cardiac troponin I are not elevated in the serum of children with acute rheumatic carditis suggests that there is minimal myocytic necrosis in this setting. This supports the concept that acute valvar regurgitation is the major hemodynamic abnormality in these patients.

Abstract 1707: Analysis Of Extracellular Matrix Remodeling On Endomyocardial Biopsies From Patients With Inflammatory Cardiomyopathy

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Olga Lettau ◽  
Susanne Rutschow ◽  
Sebastian Jaeger ◽  
Uwe Kuehl ◽  
Kerstin Puhl ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Collagen Type ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Myocardial Inflammation ◽  
Extracellular Matrix Remodeling ◽  
Type I ◽  
Matrix Remodeling ◽  
Inflammatory Cardiomyopathy ◽  
Ventricular Ejection Fraction

Introduction: The biopsy based analyse, with histological, immunohistological and molecular biological analysis of myocardial tissues, represents the only possible tool to investigate the basement of inflammatory cardiomyopathy. Since development of this disease assume involvement of extracellular matrix remodelling, the analyze of this process were aimed in this article. Methods and results: Endomyocardial biopsies from patient with inflammatory cardiomyopathy (n=170) were analysed by RT-PCR, Furthermore, histological, immunohistological and biochemical methods (ELISA) were used to estimate the matrix proteins amount in myocardial tissues (n=36). All results were obtained by comparison of patient groups regarding to left ventricular ejection fraction (LVEF), EF>60 versus EF<30. EF<30 group featured significaly increased inflammation cells per surface area: CD3 (p<0.001), CD11a (p<0.02), CD45 (p<0.02), Mac1 (p<0.02) and HLA (p<0.01). The gene expression revealed an increased transcripts number of IL-2 (p<0.01), IL-5 (p<0.01), IL-6 (p<0.02), INF beta (p<0.039), Collagen type I (p<0.001), III (p<0.0014) and IV (p<0.0004) as well Laminin (p<0.001). On the protein level ICTP (p<0.04), MMP9 (p<0.04) and TIMP I (p<0.01) were significaly increased in this group in comparison with EF>60 group. The escalating number of active CD3 cells correlated positively with BNP (ρ=0.624, p<0.0091), adhesion cell number ICAM (ρ=0.682, p<0.01) and VCAM (ρ=0.475, p<0.01) and with uPA (ρ =0.265, p<0.013), as well as with increased quantity of collagen type III per section area (ρ=0.632, p<0.01). The expanded abundance of type I collagen products was clearly dependent of the expression of collagen I gene (ρ=0.575, p<0.002) and uPA (ρ=0.544, p<0.004). Precise correlation between the amount of MMP 9 protein and downward EV values (ρ=− 0.4133, p<0.0073) was also observed in the patient group with EF<30. Conclusion: Myocardial inflammation lead to an imbalance in the MMP/TIMP system with development of myocardial fibrosis with significant correlation to LV-dysfunction. Extracellular matrix remodeling with an imbalance in the MMP/TIMP system plays an important role in the development of left ventricular dysfunction in inflammatory heart disease

Abstract 15153: Functional Cardiac Adaptation to 60 Days Strict Head-Down-Tilt Bedrest

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Fabian Hoffmann ◽  
Jeremy Rabineau ◽  
Dennis Mehrkens ◽  
Bernd W Johannes ◽  
Enrico G Caiania ◽  
...  
Keyword(s):  
Heart Rate ◽  
Cardiovascular Responses ◽  
Left Ventricular ◽  
Artificial Gravity ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Ventricular Ejection Fraction ◽  
Cardiovascular Deconditioning ◽  
Cardiac Strain ◽  
Healthy Persons

Background: Reduced physical activity increases the risk for heart failure. Myocardial strain measurements capture subtle abnormalities in myocardial function. We tested the hypothesis that bedrest deconditioning produces cardiac dysfunction in healthy persons. Methods: In the AGBRESA study, which assessed artificial gravity through centrifugation as potential countermeasure for space travel, 24 healthy persons (8 women) were submitted to 60 days strict -6°-head-down-tilt bedrest. 8 subjects each were included in a control group or groups subjected to continuous artificial gravity training on a short-arm centrifuge [30 minutes/day] or intermittent centrifugation [6x5 min/day]. We assessed cardiac morphology, function, strain and hemodynamics by cardiac-MRI (baseline, end of bedrest, recovery) and echocardiography (baseline, end of bedrest). Before and after bedrest, we assessed orthostatic heart rate responses as measure of cardiovascular deconditioning. Results: We conducted a pooled analysis because cardiovascular responses to bedrest did not differ between groups. Supine heart rate (baseline: 64±9.6bpm; bedrest: 72.3±10.5bpm; recovery: 69.6±10.5bpm, p <0.0001) and diastolic blood-pressure (69.6±7.3mmHg; bedrest: 78.5±6.9mmHg; recovery: 70.3±6.3mmHg, p <0.0001) increased with bedrest. With head-up tilt, heart rate increased 22.8±10.5bpm before and 45.9±213bpm at the end of bedrest ( p <0.0001) consistent with cardiovascular deconditioning. Cardiac-output decreased from 6.6±0.9l/min to 6±1l/min at end of bedrest (recovery: 6.8±1.2l/min, p =0.0096). Left ventricular ejection fraction and mass-index did not change. Echocardiographic global longitudinal strain (baseline: -19.90±2.1%; bedrest: -18.1±2.1%, p <0.0001) decreased, whereas global circumferential strain in MRI tended to increase (baseline: -18.6±1.7%; bedrest: -19.1±1.6%, p =0.0843). After four days of recovery MRI measurements had returned to baseline. Conclusion: In healthy persons, cardiovascular deconditioning through 60 days head-down-tilt bedrest does not lead to cardiac atrophy or sustained reductions in cardiac performance. The transient nature of cardiac strain changes suggests functional rather than structural changes in the heart.

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