scholarly journals Molecular Imaging Using Cardiac PET/CT: Opportunities to Harmonize Diagnosis and Therapy

2021 ◽  
Vol 23 (8) ◽  
Author(s):  
James T. Thackeray
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Molecular Imaging ◽  
Treatment Options ◽  
Functional Decline ◽  
Cardiac Pet ◽  
Pet Ct ◽  
Precision Therapy ◽  
Heart Failure Progression ◽  
Noninvasive Characterization

Abstract Purpose of Review Current therapeutic strategies to mitigate heart failure progression after myocardial infarction involve support of endogenous repair through molecular targets. The capacity for repair varies greatly between individuals. In this review, we will assess how cardiac PET/CT enables precise characterization of early pathogenetic processes which govern ventricle remodeling and progression to heart failure. Recent Findings Inflammation in the first days after myocardial infarction predicts subsequent functional decline and can influence therapy decisions. The expansion of anti-inflammatory approaches to improve outcomes after myocardial infarction may benefit from noninvasive characterization using imaging. Novel probes also allow visualization of fibroblast transdifferentiation and activation, as a precursor to ventricle remodeling. Summary The expanding arsenal of molecular imaging agents in parallel with new treatment options provides opportunity to harmonize diagnostic imaging with precision therapy.

scholarly journals A Review of the Molecular Mechanisms Underlying the Development and Progression of Cardiac Remodeling

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Leonardo Schirone ◽  
Maurizio Forte ◽  
Silvia Palmerio ◽  
Derek Yee ◽  
Cristina Nocella ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Remodeling ◽  
Molecular Mechanisms ◽  
Volume Overload ◽  
Cardiac Complications ◽  
Compensatory Mechanism ◽  
Myocardial Remodeling ◽  
Heart Failure Progression ◽  
Complex Signaling

Pathological molecular mechanisms involved in myocardial remodeling contribute to alter the existing structure of the heart, leading to cardiac dysfunction. Among the complex signaling network that characterizes myocardial remodeling, the distinct processes are myocyte loss, cardiac hypertrophy, alteration of extracellular matrix homeostasis, fibrosis, defective autophagy, metabolic abnormalities, and mitochondrial dysfunction. Several pathophysiological stimuli, such as pressure and volume overload, trigger the remodeling cascade, a process that initially confers protection to the heart as a compensatory mechanism. Yet chronic inflammation after myocardial infarction also leads to cardiac remodeling that, when prolonged, leads to heart failure progression. Here, we review the molecular pathways involved in cardiac remodeling, with particular emphasis on those associated with myocardial infarction. A better understanding of cell signaling involved in cardiac remodeling may support the development of new therapeutic strategies towards the treatment of heart failure and reduction of cardiac complications. We will also discuss data derived from gene therapy approaches for modulating key mediators of cardiac remodeling.

P1215Non-invasive angiogenesis assessment with PET/CT in a rabbit model of myocardial infarction: feasibility and comparison with molecular markers

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C E Grandjean ◽  
A Korshin ◽  
M Smerup ◽  
J K Jensen ◽  
B Follin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myocardial Infarction ◽  
Molecular Imaging ◽  
Sham Group ◽  
Ex Vivo ◽  
Healing Process ◽  
Rabbit Model ◽  
Infarct Area ◽  
Pet Ct ◽  
Gene Expression Alterations

Abstract Background Translational molecular imaging using Positron Emission Tomography/Computed Tomography (PET/CT) and Transesophageal Echocardiography (TEE) are powerful non-invasive tools for investigation and monitoring of cardiovascular functions. Following myocardial infarction (MI), formation of new blood vessels (angiogenesis) is of importance in the healing process and can be assessed with the PET tracer 68Ga-NODAGA-E[(cRGDyK)]2 (68Ga-RGD). Purpose The purpose of the study was to assess angiogenesis in a rabbit model of myocardial infarction using molecular imaging (PET/CT) and furthermore to validate the findings using TEE, immunohistochemistry (IHC) and quantitative PCR (qPCR). Methods Ten NZW rabbits were used (MI: n=5, SHAM: n=5). Angiogenesis was assessed with 68Ga-RGD before, 1 and 3 weeks after interventions using PET/CT (Inveon System, Siemens Health Care). TEE was used per-operatively and at termination for assessment of the MI (S8–3T probe, iE33 System, Phillips). Following the final scans, hearts were harvested for ex vivo analyses. Short axis slides were stained for collagen deposition and myocardial differentiation (H&E and Masson's trichrome), endothelial cells (CD31), and macrophage infiltration (RAM11). Gene expression alterations related to wound healing response (inflammation, granulation, and tissue remodeling) were measured using qPCR arrays (84 genes analyzed). Results One week after the interventions, 68Ga-RGD uptake, as assessed with PET was increased in the infarct area when compared to the remote zone of the same rabbit as well as compared to the SHAM group. Three weeks after intervention, there was no difference in 68Ga-RGD uptake between groups. High quality TEE images were obtained in all rabbits. Ex vivo analyses at 3 weeks after intervention revealed moderate vessel formation (CD31) in the infarct zone, none in the border zone, whereas surrounding viable myocardium had visible CD31 positive vessels comparable to the SHAM group. Macrophage infiltration (RAM11) and collagenous scaring (Masson's trichrome) was pronounced in the infarcted area. Gene expression alterations in the infarct area (30 of 84 genes upregulated) were dominated by increased expression of collagens (COL1A2, COL5A1, COL5A4), inflammatory chemokines and cytokines (CCL2, IL1A, IL1B, IL6, IL10) and ECM remodeling enzymes (uPAR, TPA, TIMP1, SERPINE1, MMP9) in the MI group compared to the SHAM group, whereas integrins involved in the angiogenesis response (ITGA4, ITGAV) were only moderately changed in the infarction at termination, confirming the in vivo PET findings. Study outline Conclusions In this rabbit MI model, we demonstrate the feasibility of monitoring angiogenesis in the healing process non-invasively with PET. The imaging results were confirmed by IHC and gene expression analysis. Moreover, TEE using a dedicated pediatric probe is feasible in the rabbit model, making this a robust and translational medium-sized animal model of myocardial infarction.

Heart failure progression is accelerated following myocardial infarction in type 2 diabetic rats

2007 ◽  
Vol 293 (3) ◽  
pp. H1609-H1616 ◽  
Author(s):  
Margaret P. Chandler ◽  
Eric E. Morgan ◽  
Tracy A. McElfresh ◽  
Theodore A. Kung ◽  
Julie H. Rennison ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Contractile Dysfunction ◽  
Lv Dysfunction ◽  
Lv Remodeling ◽  
Heart Failure Progression ◽  
Type 2 Diabetic

Clinical studies have shown a greater incidence of myocardial infarction in diabetic patients, and following an infarction, diabetes is associated with an increased risk for the development of left ventricular (LV) dysfunction and heart failure. The goal of this study was to determine if the progression of heart failure following myocardial infarction in type 2 diabetic (T2D) rats is accelerated compared with nondiabetic rats. Male nondiabetic Wistar-Kyoto (WKY) and T2D Goto-Kakizaki (GK) rats underwent coronary artery ligation or sham surgery to induce heart failure. Postligation (8 and 20 wk), two-dimensional echocardiography and LV pressure measurements were made. Heart failure progression, as assessed by enhanced LV remodeling and contractile dysfunction, was accelerated 8 wk postligation in the T2D animals. LV remodeling was evident from increased end-diastolic and end-systolic diameters and areas in the GK compared with the WKY infarcted group. Furthermore, enhanced LV contractile dysfunction was evident from a greater deterioration in fractional shortening and enhanced myocardial performance index (an index of global LV dysfunction) in the GK infarcted group. This accelerated progression was accompanied by greater increases in atrial natriuretic factor and skeletal α-actin (gene markers of heart failure and hypertrophy) mRNA levels in GK infarcted hearts. Despite similar decreases in metabolic gene expression (i.e., peroxisome proliferator-activated receptor-α-regulated genes associated with fatty acid oxidation) between infarcted WKY and GK rat hearts, myocardial triglyceride levels were elevated in the GK hearts only. These results, demonstrating enhanced remodeling and LV dysfunction 8 wk postligation provide evidence of an accelerated progression of heart failure in T2D rats.

scholarly journals Histidine triad nucleotide-binding protein 2 protects cardiomyocytes via maintaining NAD homeostasis in virto and in vivo

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
F Mengkang ◽  
Y.I.N Huang ◽  
J Qian
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Molecular Docking ◽  
Nucleotide Binding ◽  
Metabolic Status ◽  
Funding Source ◽  
Targeted Metabolomics ◽  
Pet Ct

Abstract Background Heart failure (HF) is the end-stage of most heart diseases with poor clinical outcomes. The mitochondrial dysfunction is a critical therapeutic target in HF, and the histidine triad nucleotide-binding (HINT2) protein has been shown to enhance energy metabolism in liver. However, the role of HINT2 in HF remains unclear. Purpose To explore the role of the histidine triad nucleotide-binding 2 (HINT2) protein in heart failure. Methods Neonatal mouse ventricle myocytes (NMVMs) and myocardial infarction-induced heart failure mice were used for in vitro or in vivo experiments. Adenovirus (ADV) and adeno-associated virus serum type 9 (AAV9) vectors were used to regulate HINT2 expression. The expression of HINT2 was determined by quantifying the mRNA and protein levels. Cell survival was analysed using the CCK-8 kit and TUNEL staining. Mitochondrial function was determined by the mitochondrial membrane potential and oxygen consumption rates. AAV9-HINT2 was injected 24 h post myocardial infarction following which transthoracic echocardiography and histological analyses were performed after 4 weeks. Positron emission tomography tomography-computed tomography (PET/CT) and targeted metabolomics analyses were used to explore the metabolic status in vivo. NAD levels were measured using a colorimetric kit. Computer-simulated rigid body molecular docking was performed using AUTODOCK4. Molecule binding kinetics assays were performed using biolayer interferometry. Results After 12 hours hypoxia stimuli, HINT2 was down regulated. ADV-HINT2 induced HINT2 overexpression improved NMVMs survival and reduced apoptosis after hypoxia. MMP was reduced in ADV-shHINT2 group and was preserved in ADV-HINT2 group under hypoxia. HINT2 overexpressed NMVMs showed less reduction in basal, ATP-linked and maximum OCR after hypoxia stimuli. In vivo experiment, showed that cardiac function and metabolic status was preserved by HINT2 overexpression. PET/CT displayed glucose uptake ability was significantly reduced in in failing heart, which was preserved by overexpression of HINT2. Targeted metabolomics analysis showed that nicotinate and nicotinamide metabolism pathway was regulated by HINT2, in which oxidized state NAD (NAD+) and redox state NAD (NADH) was increased in AAV9-HINT2 group. NAD concentration was detected in NMVMs. HINT2 can improve total NAD level rather than ratio of NAD+/NADH, and its effect was limited into mitochondria.HINT2 overexpression restored mitochondrial NAD levels; this was dependent on nicotinamide mononucleotide (NMN). Using computer-simulated molecular docking analysis and biolayer interferometry, we observed that HINT2 potentially binds and associates with NMN. Conclusion In summary, these findings demonstrate that the HINT2 is beneficial to preserve the heart function and metabolism in the HF murine model after acute MI, and this positive effect may due to the maintenance of mitochondrial NAD homeostasis. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China (Grant Nos: 81970295, 81870267)

Abstract 295: Enhanced Cardiac Function And Lower Circulating Aldosterone Levels In βArrestin1 Knockout Mice During Post-myocardial Infarction Heart Failure Progression

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Anastasios Lymperopoulos ◽  
Giuseppe Rengo ◽  
Erhe Gao ◽  
Ashley Siryk ◽  
Samalia Dabul ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Function ◽  
Underlying Mechanism ◽  
Post Myocardial Infarction ◽  
Aldosterone Production ◽  
Heart Failure Progression ◽  
Adverse Remodeling ◽  
And Function

Introduction: Chronic heart failure (HF) is characterized by enhanced circulating cardiotoxic hormones, among the most prominent of which is aldosterone, which contributes to the increased morbidity and mortality of the disease by promoting cardiac adverse remodeling post-myocardial infarction (MI). Cardiac β-adrenergic receptor (ΑR) desensitization and downregulation are a hallmark abnormality in HF at the molecular level and are due to the concerted action of cardiac G protein-coupled receptor kinase-2 (GRK2), together with its co-factors in receptor desensitization, the βarrestins (βarrs). We have also recently established that βarr1 promotes angiotensin II-dependent aldosterone production in the adrenal cortex, and this leads to elevated circulating aldosterone levels in vivo, both under normal conditions and during post-MI HF progression. Hypothesis: Herein, we sought to investigate the effects of genetically deleting βarr1 on post-MI cardiac function and hyperaldosteronic status in mice progressing to HF. Methods: We uitilized the βarr1KO mouse model and studied these mice at 4 weeks after surgically induced MI, in parallel with C57/B6 wild type (WT) controls. Cardiac function was assessed by echocardiography and in vivo catheterization. Plasma aldosterone was measured by ELISA. Results: Cardiac function is markedly improved in βarr1KO`s at 4 weeks post-MI, as evidenced by increased ejection fraction compared to WT mice (41.5 + 2.8 % vs. 21.8 + 2.4 %, respectively, n=9, p<0.0001) and increased isoproterenol-induced contractility. Additionally, cardiac dimensions are significantly reduced compared to WT`s, indicating attenuation of adverse cardiac remodeling. Importantly, plasma circulating aldosterone levels are significantly lowered and cardiac βAR signaling and function appear elevated in post-MI βarr1KO`s compared to control WT`s. Conclusions: Genetic deletion of βarr1 substantially improves cardiac function, adverse remodeling, hyperaldosteronism, and cardiac βAR function during post-MI HF progression. The underlying mechanism is attenuation of both cardiac βAR desensitization/downregulation and adrenal aldosterone production, which is βarr1-dependent.

The management of acute pericarditis

2005 ◽  
Vol 4 (2) ◽  
pp. 47-50
Author(s):  
Tim Wells ◽  
◽  
NP Curzen ◽  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Pulmonary Embolism ◽  
Treatment Options ◽  
Acute Chest Pain ◽  
Acute Pericarditis ◽  
Viral Aetiology ◽  
Underlying Causes ◽  
The Common ◽  
Limiting Condition

Acute pericarditis is usually a benign self-limiting condition, often of unexplained or viral aetiology, involving inflammation of the pericardial layers. It is often part of the differential diagnosis in patients admitted with acute chest pain and can be confused with acute myocardial infarction, acute pulmonary embolism and pleurisy. Occasionally it can result in cardiac tamponade and, if associated with myocarditis, in heart failure. This article sets out how to diagnose acute pericarditis, the common underlying causes, the possible treatment options and outcomes.

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