scholarly journals Protective Effects of Meldonium in Experimental Models of Cardiovascular Complications with a Potential Application in COVID-19

2021 ◽  
Vol 23 (1) ◽  
pp. 45
Author(s):  
Reinis Vilskersts ◽  
Dana Kigitovica ◽  
Stanislava Korzh ◽  
Melita Videja ◽  
Karlis Vilks ◽  
...  

Right ventricular (RV) and left ventricular (LV) dysfunction is common in a significant number of hospitalized coronavirus disease 2019 (COVID-19) patients. This study was conducted to assess whether the improved mitochondrial bioenergetics by cardiometabolic drug meldonium can attenuate the development of ventricular dysfunction in experimental RV and LV dysfunction models, which resemble ventricular dysfunction in COVID-19 patients. Effects of meldonium were assessed in rats with pulmonary hypertension-induced RV failure and in mice with inflammation-induced LV dysfunction. Rats with RV failure showed decreased RV fractional area change (RVFAC) and hypertrophy. Treatment with meldonium attenuated the development of RV hypertrophy and increased RVFAC by 50%. Mice with inflammation-induced LV dysfunction had decreased LV ejection fraction (LVEF) by 30%. Treatment with meldonium prevented the decrease in LVEF. A decrease in the mitochondrial fatty acid oxidation with a concomitant increase in pyruvate metabolism was noted in the cardiac fibers of the rats and mice with RV and LV failure, respectively. Meldonium treatment in both models restored mitochondrial bioenergetics. The results show that meldonium treatment prevents the development of RV and LV systolic dysfunction by enhancing mitochondrial function in experimental models of ventricular dysfunction that resembles cardiovascular complications in COVID-19 patients.

2021 ◽  
Vol 64 (2) ◽  
pp. 70-78
Author(s):  
Iulia Rodoman ◽  
◽  
Ina Palii ◽  
Victoria Sacara ◽  
Sergiu Gladun ◽  
...  

Background: Cardiomyopathy (CM) associated with Duchenne muscular dystrophy (DMD) is a commonly recognized appearance of this neuromuscular disease, significantly increased morbidity and mortality, as well as the necessity for cardiological management. CM in DMD is defined by left ventricular (LV) systolic dysfunction and both atrial and ventricular dysrhythmias and is associated with higher mortality than other cases of pediatric dilated CMs. Notwithstanding the high rate of cardiac involvement, patients are usually asymptomatic despite significant LV dysfunction, because of likely poor mobility that masks the usual heart failure (HF) symptoms. Also, imagistic predictors are provided to be very helpful in defining early LV dysfunction, especially electrocardiogram and cardiac imaging (transthoracic echocardiography, speckle-tracking, cardiac magnetic resonance) are used to detect the onset and progression of dilated cardiomyopathy (DCM) in DMD. Conclusions: As most DMD patients are asymptomatic for a long time of their life, so identifying predictors of HF is crucial to support these patients. Ventricular dysfunction based on the ejection fraction (EF) measurement helps to choose therapy. In the case of early DCM (LVEF≥50%) the great purpose is to prevent ventricular dysfunction incipience with first-line HF therapy with Angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARBs). Current guidelines recommend the use of conventional HF medication in case of disease progression and DCM with MidRange Reduction of LV EF (40-49%). The therapeutic approach for patients with DCM and severe ventricular dysfunction (<40%) has been studied less profoundly and contemporary guidelines recommend all drugs used for HF treatment


2021 ◽  
Vol 31 (1) ◽  
pp. 122-128
Author(s):  
Ionela Simona Visoiu ◽  
Roxana Cristina Rimbas ◽  
Loredana Gheorghiu ◽  
Ruxandra Dragoi Galrinho Antunes Guerra ◽  
Alina Ioana Nicula ◽  
...  

Left ventricular non-compaction (LVNC) is an increasingly recognized phenotype. The current definition of the LVNC does not mention LV dysfunction as an absolute criterion in addition to morphological criteria. LV dilatation and decreased LV ejection fraction (LVEF) are often late manifestations of the disease and correlate with the occurrence of cardiovascular complications. However, to define LVNC as a cardiomyopathy, functional criteria must be fulfilled, in addition to the morphological ones. Multimodality imaging, such as myocardial deformation and myocardial work analysis derived from speckle tracking echocardiography (STE), in combination with cardiac magnetic resonance (CMR) might improve diagnosis and characterization of non-compaction, exposing earlier signs of LV systolic dysfunction. We present two comparative cases of LVNC in order to highlight the idea of subclinical dysfunction even in apparently benign forms with preserved LVEF, and also the importance of multimodality imaging approach.


2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Tsunehisa Yamamoto ◽  
Kirill Batmanov ◽  
Elizabeth Pruzinsky ◽  
Yang Xiao ◽  
Swapnil V Shewale ◽  
...  

During the development of heart failure (HF), the PPAR/ERR complex becomes deactivated resulting in diminished capacity for mitochondrial fatty acid oxidation (FAO) and ATP production leading to an “energy-starved” state that contributes to progression of HF. Receptor-Interacting protein 140 (RIP140) serves as a co-repressor of PPAR/ERR in some extra-cardiac tissues. We hypothesized that inhibition of RIP140 would re-activate PPAR/ERR enhancing capacity for fuel catabolism and ATP production in the failing heart. Heart and skeletal muscle-specific RIP140 knockout mice (strRIP140KO) were resistant to the development of cardiac hypertrophy and diastolic dysfunction in response to chronic pressure overload that mimicked features of HF with preserved ejection fraction (HFpEF). To further evaluate the role of RIP140 in heart, cardiac-specific (cs) RIP140KO mice were generated. 13 C-substrate NMR studies demonstrated that palmitate oxidation and triglyceride turnover rates were significantly accelerated in isolated perfused csRIP140KO hearts. csRIP140KO were subjected to transverse aortic constriction/apical myocardial infarction surgery (TAC/MI), to produce HF with reduced EF (HFrEF). Compared to controls, csRIP140KO exhibited reduced left ventricular remodeling and systolic dysfunction when subjected to TAC/MI. RNA-sequence analysis demonstrated that many genes involved in FAO, branched-chain amino acid catabolism, oxidative phosphorylation, and adult muscle contraction programs were significantly “protected” (less downregulation) by RIP140 deletion in the context of TAC/MI. To identify candidate cardiac RIP140 targets, “CUT&RUN”-sequencing was conducted on cardiomyocytes (CM) from csRIP140KO and controls to identify changes in enhancer regions. Motif analysis of peaks with increased H3K27ac deposition in the csRIP140KO CM identified ERR, PPAR, myocyte enhancer 2 (MEF2), glucocorticoid receptor (GR), and kruppel-like factor (KLF) binding sites. We conclude that RIP140 serves as a global co-repressor of a network of transcription factors that control cardiac energy metabolic and contractile function, and that inhibition of RIP140 could prove to be a novel therapeutic approach for HF.


2019 ◽  
Author(s):  
Helena Urquijo ◽  
Emma N Panting ◽  
Roderick N Carter ◽  
Emma J Agnew ◽  
Caitlin S Wyrwoll ◽  
...  

1991 ◽  
Vol 266 (34) ◽  
pp. 22932-22938
Author(s):  
R.S. Kler ◽  
S. Jackson ◽  
K. Bartlett ◽  
L.A. Bindoff ◽  
S. Eaton ◽  
...  

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1510.1-1511
Author(s):  
T. Kuga ◽  
M. Matsushita ◽  
K. Tada ◽  
K. Yamaji ◽  
N. Tamura

Background:Cardiovascular disease (CVD) is detected in up to 50% of systemic lupus erythematosus (SLE) patients1and major cause of death2. Even clinically silent SLE patients can develop left ventricular (LV) diastolic dysfunction3. Proper echocardiographic follow up of SLE patients is required.Objectives:To clarify how the prevalence of LV abnormalities changes over follow-up period and identify the associated clinical factors, useful in suspecting LV abnormalities.Methods:29 SLE patients (24 females and 5 men, mean age 52.8±16.3 years, mean disease duration 17.6±14.5 years) were enrolled. All of them underwent echocardiography as the baseline examination and reexamined over more than a year of follow-up period(mean 1075±480 days) from Jan 2014 to Sep 2019. Patients complicated with pulmonary artery hypertension, deep venous thrombosis or pulmonary embolism and underwent cardiac surgery during the follow-up period were excluded. Left ventricular(LV) systolic dysfunction was defined as ejection fraction (EF) < 50%. LV diastolic dysfunction was defined according to ASE/EACVI guideline4. LV dysfunction (LVD) includes one or both of LV systolic dysfunction and LV diastolic function. Monocyte to HDL ratio (MHR) was calculated by dividing monocyte count with HDL-C level.Prevalence of left ventricular abnormalities was analysed at baseline and follow-up examination. Clinical characteristics and laboratory data were compared among patient groups as follows; patients with LV dysfunction (Group A) and without LV dysfunction (Group B) at the follow-up echocardiography, patients with LV asynergy at any point of examination (Group C) and patients free of LV abnormalities during the follow-up period (Group D).Results:At the baseline examination, LV dysfunction (5/29 cases, 13.8%), LV asynergy (6/29 cases, 21.7%) were detected. Pericarditis was detected in 7 patients (24.1%, LVD in 3 patients, LV asynergy in 2 patients) and 2 of them with subacute onset had progressive LV dysfunction, while 5 patients were normal in echocardiography after remission induction therapy for SLE. At the follow-up examination, LV dysfunction (9/29 cases, 31.0%, 5 new-onset and 1 improved case), LV asynergy (6/29 cases, 21.7%, 2 new-onset and 2 improved cases) were detected. Though any significant differences were observed between Group A and Group B at the baseline, platelet count (156.0 vs 207.0, p=0.049) were significantly lower in LV dysfunction group (Group A) at the follow-up examination. Group C patients had significantly higher uric acid (p=0.004), monocyte count (p=0.009), and MHR (p=0.003) than Group D(results in table).Conclusion:LV dysfunction is progressive in most of patients and requires regular follow-up once they developed. Uric acid, monocyte count and MHR are elevated in SLE patients with LV asynergy. Since MHR elevation was reported as useful marker of endothelial dysfunction5, our future goal is to analyse involvement of monocyte activation and endothelial dysfunction in LV asynergy of SLE patients.References:[1]Doria A et al. Lupus. 2005;14(9):683-6.[2]Manger K et al. Ann Rheum Dis. 2002 Dec;61(12):1065-70.[3]Leone P et al. Clin Exp Med. 2019 Dec 17.[4]Nagueh SF et al. J Am Soc Echocardiogr. 2016 Apr;29(4):277-314.[5]Acikgoz N et al. Angiology. 2018 Jan;69(1):65-70.Numbers are median (interquartile range), Mann-Whitney u test were performed, p value less than 0.05 was considered statistically significant.Disclosure of Interests: :None declared


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