scholarly journals Altered mRNA Expression of Interleukin-1 Receptors in Myocardial Tissue of Patients with Left Ventricular Assist Device Support

2021 ◽  
Vol 10 (21) ◽  
pp. 4856
Author(s):  
Naima Niazy ◽  
Linus Mrozek ◽  
Mareike Barth ◽  
Moritz Benjamin Immohr ◽  
Nikolaos Kalampokas ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mrna Expression ◽  
Interleukin 1 ◽  
Left Ventricular ◽  
Receptor Expression ◽  
Circulatory Support ◽  
Cytokine Signaling ◽  
Myocardial Tissue ◽  
Expression Levels ◽  
Local Cytokine

Serum levels of cytokines interleukin 1 beta (IL-1β) and interleukin 33 (IL-33) are highly abnormal in heart failure and remain elevated after mechanical circulatory support (MCS). However, local cytokine signaling induction remains elusive. Left (LV) and right ventricular (RV) myocardial tissue specimens of end-stage heart failure (HF) patients without (n = 24) and with MCS (n = 39; 594 ± 57 days) were analyzed for cytokine mRNA expression level of IL-1B, interleukin 1 receptor 1/2 (IL-1R1/2), interleukin 1 receptor-like 1 (IL-1RL1), IL-33 and interleukin-1 receptor accessory protein (IL-1RaP). MCS patients showed significantly elevated IL-1B expression levels (LV: 2.0 fold, p = 0.0058; RV: 3.3 fold, p < 0.0001). Moreover, IL-1R1, IL-1RaP and IL-33 expression levels strongly correlated with each other. IL-1RL1 and IL-1R2 expression levels were significantly higher in RV myocardial tissue (RV/LV ratio IL-1R2 HF: 4.400 ± 1.359; MCS: 4.657 ± 0.655; IL-1RL1 HF: 3.697 ± 0.876; MCS: 4.529 ± 0.5839). In addition, IL1-RaP and IL-33 RV expression levels were significantly elevated in MCS. Furthermore, IL-33 expression correlates with C-reactive protein (CRP) plasma levels in HF, but not in MCS patients. Increased expression of IL-1B and altered correlation patterns of IL-1 receptors indicate enhanced IL-1β signaling in MCS patients. Correlation of IL-1 receptor expression with IL-33 may hint towards a link between both pathways. Moreover, diverging expression in LV and RV suggests specific regulation of local cytokine signaling.

scholarly journals Myocardial perfusion and cardiac dimensions during extracorporeal membrane oxygenation–supported circulation in a porcine model of critical post-cardiotomy failure

Perfusion ◽  
2020 ◽  
Vol 35 (8) ◽  
pp. 763-771
Author(s):  
Atle Solholm ◽  
Pirjo-Riitta Salminen ◽  
Lodve Stangeland ◽  
Christian Arvei Moen ◽  
Arve Mongstad ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiopulmonary Bypass ◽  
Myocardial Perfusion ◽  
Extracorporeal Membrane Oxygenation ◽  
Left Ventricular ◽  
Circulatory Support ◽  
Myocardial Tissue ◽  
Membrane Oxygenation ◽  
Venoarterial Extracorporeal Membrane Oxygenation ◽  
Tissue Oedema

Introduction: Venoarterial extracorporeal membrane oxygenation is widely used as mechanical circulatory support for severe heart failure. A major concern with this treatment modality is left ventricular distension due to inability to overcome the afterload created by the extracorporeal membrane oxygenation circuit. The present porcine study evaluates coronary circulation, myocardial perfusion and ventricular distension during venoarterial extracorporeal membrane oxygenation. Methods: Ten anesthetized open-chest pigs were cannulated and put on cardiopulmonary bypass. Heart failure was achieved by 90 minutes of aortic cross-clamping with insufficient cardioplegic protection. After declamping, the animals were supported by venoarterial extracorporeal membrane oxygenation for 3 hours. Continuous haemodynamic measurements were performed at baseline, during cardiopulmonary bypass/aortic cross-clamping and during venoarterial extracorporeal membrane oxygenation. Fluorescent microsphere injections at baseline and after 1, 2 and 3 hours on venoarterial extracorporeal membrane oxygenation evaluated myocardial perfusion. Left ventricular function and distension were assessed by epicardial echocardiography. Results: The myocardial injury caused by 90 minutes of ischaemia resulted in a poorly contracting myocardium, necessitating venoarterial extracorporeal membrane oxygenation in all animals. The circulatory support maintained the mean arterial blood pressure within a satisfactory range. A hyperaemic left anterior descending coronary artery flow while on extracorporeal membrane oxygenation was observed compared to baseline. Myocardial tissue perfusion measured by microspheres was low, especially in the subendocardium. Echocardiography revealed myocardial tissue oedema, a virtually empty left ventricle, and a left ventricular output that remained negligible throughout the extracorporeal membrane oxygenation run. Conclusion: Coronary artery blood flow is maintained during venoarterial extracorporeal membrane oxygenation after cardiopulmonary bypass and cardioplegic arrest despite severely affected performance of the left ventricle. Myocardial perfusion decreases, however, presumably due to rapid development of myocardial tissue oedema.

scholarly journals Aetiology-dependent impairment of mitochondrial function in the failing human heart

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Borger ◽  
D Scheiber ◽  
P Horn ◽  
D Pesta ◽  
U Boeken ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mitochondrial Function ◽  
Human Study ◽  
Left Ventricular ◽  
Myocardial Tissue ◽  
Funding Source ◽  
Ros Production ◽  
German Research Foundation ◽  
Long Term Outcome ◽  
Tissue Specimens

Abstract Background Alterations of mitochondrial function have been identified to play a role in Heart Failure (HF) pathophysiology. Oxidative phosphorylation (OXPHOS) capacity of the myocardium was shown to be reduced in the failing heart. Ineffective mitochondrial function promotes formation of reactive oxygen species (ROS) that may affect remodelling in ischemia. Thus far, human mitochondrial function comparing dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) resembling the main aetiologies of heart failure with reduced ejection fraction (HFrEF) has not been investigated. Purpose We hypothesised that 1. ROS production is elevated in left ventricular myocardial tissue specimens of ICM patients compared to DCM. 2. Mitochondrial OXPHOS capacity is higher in left ventricular myocardial tissue specimens of DCM compared to ICM patients. Methods Myocardial tissue was obtained from the left ventricular apex from 63 patients (38 ICM, 25 DCM) with advanced HFrEF requiring implantation of a Left Ventricular Assist Device (LVAD). We performed high-resolution respirometry (HRR, OROBOROS Oxygraph-2k) in saponine-permeabilised myocardial fibres and measured ROS production fluoroscopically via the Amplex Red method. Statistical analysis was conducted using GraphPad Prism 7 and IBM SPSS v26.0. Results Groups were of comparable age (61.5±1.2 vs. 59.3±2.4 years, p=n.s.), sex (87% vs 85% male, p=n.s.), diabetic status (32% vs 38.4% type 2 diabetes mellitus, p=n.s.), and body mass index (28.1±0.8 vs. 26.3±1.1 kg/m2, p=n.s.). We detected reduced myocardial mitochondrial OXPHOS capacity in ICM under state 3 conditions by about 15% (68.7±34.0 vs. 80.9±30.5 pmol/(s*mg), p&lt;0.05), after addition of Glutamate by 25% (78.9±38.7 vs. 104.8±41.2 pmol/(s*mg), p&lt;0.01) as well as after Succinate (115.5±65.5 vs. 155±62.0 pmol/(s*mg), p&lt;0.01), uncoupling agent FCCP (114.1±56.8 vs. 150.5±47.3 pmol/(s*mg), p&lt;0.01), and by about 40% after addition of Complex I inhibitor Rotenone (55.5±25.9 vs. 96.9±28.0 pmol/(s*mg), p&lt;0.001). We detected no difference in ROS production between ICM and DCM (0.6±0.05 vs. 0.76±0.08 pmol/(s*ml), p=n.s.). Conclusion This is the first human study deciphering distinct alterations in mitochondrial function (OXPHOS capacity) in ventricular myocardium of HFrEF patients. Future studies may address how distinct metabolic patterns at the time of implantation may relate to long-term outcome of HFrEF in terms of remodelling and recovery. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): DFG (German Research Foundation)

scholarly journals Can mechanical circulatory support be an effective treatment for HFpEF patients?

2021 ◽  
Author(s):  
Einar Gude ◽  
Arnt E. Fiane
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Mechanical Circulatory Support ◽  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Left Ventricular Cavity ◽  
Circulatory Support ◽  
Left Ventricular Assist Devices ◽  
Mechanical Pressure ◽  
Entry Points

AbstractHeart failure with preserved ejection fraction (HFpEF) is increasing in prevalence and represents approximately 50% of all heart failure (HF) patients. Patients with this complex clinical scenario, characterized by high filling pressures, and reduced cardiac output (CO) associated with progressive multi-organ involvement, have so far not experienced any significant improvement in quality of life or survival with traditional HF treatment. Left ventricular assist devices (LVAD) have offered a new treatment alternative in terminal heart failure patients with reduced ejection fraction (HFrEF), providing a unique combination of significant pressure and volume unloading together with an increase in CO. The small left ventricular cavity in HFpEF patients challenges left-sided pressure unloading, and new anatomical entry points need to be explored for mechanical pressure and volume unloading. Optimized and pressure/volume-adjusted mechanical circulatory support (MCS) devices for HFrEF patients may conceivably be customized for HFpEF anatomy and hemodynamics. We have developed a long-term MCS device for HFpEF patients with atrial unloading in a pulsed algorithm, leading to a significant reduction of filling pressure, maintenance of pulse pressure, and increase in CO demonstrated in animal testing. In this article, we will discuss HFpEF pathology, hemodynamics, and the principles behind our novel MCS device that may improve symptoms and prognosis in HFpEF patients. Data from mock-loop hemolysis studies, acute, and chronic animal studies will be presented.

Abstract 17097: Non-Synonymous Mitochondrial DNA Variants Are Common in Myocardial Tissue of Heart Failure Patients

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Pappu Ananya ◽  
Michael Binder ◽  
Yang Wanjun ◽  
Rebecca McClellan ◽  
Brittney Murray ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mitochondrial Dna ◽  
Nuclear Dna ◽  
Left Ventricular ◽  
Individual Risk ◽  
Myocardial Tissue ◽  
Mtdna Mutation ◽  
Mtdna Mutations ◽  
Ventricular Tissue ◽  
Mtdna Variants

Introduction: Mitochondrial heart disease due to pathogenic mitochondrial DNA (mtDNA) mutations can present as hypertrophic or dilated cardiomyopathy, ventricular arrhythmias and conduction disease. It is estimated that the mutation rate of mtDNA is 10 to 20-fold higher than that of nuclear DNA genes due to damage from reactive oxygen species released as byproducts during oxidative phosphorylation. When a new mtDNA mutation arises, it creates an intracellular heteroplasmic mixture of mutant and normal mtDNAs, called heteroplasmy. Heteroplasmy levels can vary in various tissues and examining mtDNA variants in blood may not be representative for the heart. The frequency of pathogenic mtDNA variants in myocardial tissues in unknown. Hypothesis: Human ventricular tissue may contain mtDNA mutations which can lead to alterations in mitochondrial function and increase individual risk for heart failure. Methods: Mitochondrial DNA was isolated from 61 left ventricular myocardial samples obtained from failing human hearts at the time of transplantation. mtDNA was sequenced with 23 primer pairs. In silico prediction of non-conservative missense variants was performed via PolyPhen-2. Heteroplasmy levels of variants predicted to be pathogenic were quantified using allele-specific ARMS-PCR. Results: We identified 21 mtDNA non-synonymous variants predicted to be pathogenic in 17 hearts. Notably, one heart contained four pathogenic mtDNA variants (ATP6: p.M104; ND5: p.P265S; ND4: p.N390S and p.L445F). Heteroplasmy levels exceeded 90% for all four variants in myocardial tissue and were significantly lower in blood. No pathogenic mtDNA variants were identified in 44 hearts. Hearts with mtDNA mutations had higher levels of myocardial GDF-15 (growth differentiation factor-15; 6.2±2.3 vs. 1.3±0.18, p=0.045), an established serum biomarker in various mitochondrial diseases. Conclusions: Non-synonymous mtDNA variants predicted to be pathogenic are common in human left ventricular tissue and may be an important modifier of the heart failure phenotype. Future studies are necessary to correlate myocardial mtDNA mutations with cardiovascular outcomes and to assess whether serum GDF-15 allows identifying patients with myocardial mtDNA mutations.

Abstract 814: Atorvastatin Attenuates Oxidative Stress And Improves Neuronal Nitric Oxide Synthase In The Brain Stem Of Heart Failure Mice

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Joseph Francis ◽  
Li Yu ◽  
Anuradha Guggilam ◽  
Srinivas Sriramula ◽  
Irving H Zucker
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Brain Stem ◽  
Mrna Expression ◽  
Natriuretic Peptide ◽  
Left Ventricular ◽  
Neuronal Nos ◽  
The Brain

3-Hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to reduce the incidence of myocardial infarction independent of their lipid-lowering effects. Nitric oxide (NO) in the central nervous system contributes to cardiovascular regulatory mechanisms. Imbalance between nitric oxide (NO) and superoxide anion (O 2 . − ) in the brain may contribute to enhanced sympathetic drive in heart failure (HF). This study was done to determine whether treatment with atorvastatin (ATS) ameliorates the imbalance between NO and O 2 . − production in the brain stem and contributes to improvement of left ventricular (LV) function. Methods and Results: Myocardial infarction (MI) was induced by ligation of the left coronary artery or sham surgery. Subsequently, mice were treated with ATS (10 μg/kg) (MI + ATS), or vehicle (MI + V). After 5 weeks, echocardiography revealed left ventricular dilatation in MI mice. Realtime RT-PCR indicated an increase in the mRNA expression of the LV hypertrophy markers, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Neuronal NOS (nNOS) and endothelial NOS (eNOS) mRNA expression were significantly reduced, while that of NAD(P)H oxidase subunit (gp91phox) expression was elevated in the brain stem of MI mice. Compared with sham-operated mice, ATS-treated mice showed reduced cardiac dilatation, decreased ANP and BNP in the LV. ATS also reduced gp91phox expression and increased nNOS mRNA expression in the brain stem, while no changes in eNOS and iNOS were observed. Conclusion: These findings suggest that ATS reduces oxidative stress and increases neuronal NOS in the brain stem, and improves left ventricular function in heart failure.

scholarly journals Evaluating the Hemodynamical Response of a Cardiovascular System under Support of a Continuous Flow Left Ventricular Assist Device via Numerical Modeling and Simulations

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Selim Bozkurt ◽  
Koray K. Safak
Keyword(s):  
Heart Failure ◽  
Cardiovascular System ◽  
Left Ventricular Assist Device ◽  
Ventricular Assist Device ◽  
Continuous Flow ◽  
Left Ventricular ◽  
Circulatory Support ◽  
Assist Device ◽  
Ventricular Assist ◽  
Left Ventricular Assist

Dilated cardiomyopathy is the most common type of the heart failure which can be characterized by impaired ventricular contractility. Mechanical circulatory support devices were introduced into practice for the heart failure patients to bridge the time between the decision to transplant and the actual transplantation which is not sufficient due to the state of donor organ supply. In this study, the hemodynamic response of a cardiovascular system that includes a dilated cardiomyopathic heart under support of a newly developed continuous flow left ventricular assist device—Heart Turcica Axial—was evaluated employing computer simulations. For the evaluation, a numerical model which describes the pressure-flow rate relations of Heart Turcica Axial, a cardiovascular system model describing the healthy and pathological hemodynamics, and a baroreflex model regulating the heart rate were used. Heart Turcica Axial was operated between 8000 rpm and 11000 rpm speeds with 1000 rpm increments for assessing the pump performance and response of the cardiovascular system. The results also give an insight about the range of the possible operating speeds of Heart Turcica Axial in a clinical application. Based on the findings, operating speed of Heart Turcica Axial should be between 10000 rpm and 11000 rpm.

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