scholarly journals Cellular aging and rejuvenation in ischemic heart disease: a translation from basic science to clinical therapy

2022 ◽  
Author(s):  
Rosalinda Madonna

Ischemic heart disease and heart failure (HF) remain the leading causes of death worldwide. The inability of the adult heart to regenerate itself following ischemic injury and subsequent scar formation may explain the poor prognosis in these patients, especially when necrosis is extensive and leads to severe left ventricular dysfunction. Under physiological conditions, the crosstalk between cardiomyocytes and cardiac interstitial/vascular cells plays a pivotal role in cardiac processes by limiting ischemic damage or promoting repair processes, such as angiogenesis, regulation of cardiac metabolism, and the release of soluble paracrine or endocrine factors. Cardiovascular risk factors are the main cause of accelerated senescence of cardiomyocytes and cardiac stromal cells (CSCs), causing the loss of their cardioprotective and repairing functions. CSCs are supportive cells found in the heart. Among these, the pericytes/mural cells have the propensity to differentiate, under appropriate stimuli in vitro, into adipocytes, smooth muscle cells, osteoblasts, and chondroblasts, as well as other cell types. They contribute to normal cardiac function and have an antifibrotic effect after ischemia. Diabetes represents a condition of accelerated senescence. Among the new pharmacological armamentarium with hypoglycemic effect, gliflozins have been shown to reduce the incidence of HF and re-hospitalization, probably through the anti-remodeling and anti-senescent effect on the heart, regardless of diabetes. Therefore, either reducing the senescence of CSC or removing senescent cells from the infarcted heart could represent future antisenescence strategies capable of preventing the deterioration of heart function leading to HF.

2010 ◽  
Vol 2 ◽  
pp. CMT.S3159
Author(s):  
Anna Salerno ◽  
Gabriele Fragasso ◽  
Claudia Montanaro ◽  
Michela Cera ◽  
Camilla Torlasco ◽  
...  

Coronary artery disease (CAD) is a major cause of morbidity and mortality in the world. Therapy for stable CAD is currently based on conventional medical therapy, including nitrates, β-blockers and calcium-channels antagonists and, more recently, metabolic therapy, of which a pivotal therapeutic role is increasingly recognized. Under normoxic condition, the healthy heart derives 2/3 of its energy from the free fatty acid (FFA) pathway, the other source of energy being derived from glucose oxidation. However, glycolysis requires less O2 per mole of ATP generated compared with FFA oxidation. On this basis, shifting energy substrate utilization from fatty acid metabolism to glucose metabolism can be more efficient in terms of ATP production per mole of oxygen utilized. A number of different approaches have been used to manipulate energy metabolism in the heart. These approaches include direct agents, such as dichloroacetate, L-carnitine, ribose or lipoic acid which directly increase glucose oxidation, or indirect methods, through the inhibition of free fatty acids oxidation. Among these, the most important are carnitil-palmitoyl-transpherase I (CPT-I) inhibitors, which inhibit FFA mitochondrial uptake (e.g. etomoxir, perhexiline, oxphenicine), or 3-ketoacyl-coenzyme-A thiolase (3-KAT) inhibitors, such as trimetazidine, which inhibits the last enzyme involved in β-oxidation. In most patients with ischemic heart disease metabolic abnormalities, if not adequately treated, will heavily contribute to the occurrence of complications, of whom severe left ventricular dysfunction is at present one of the most frequent and insidious. In this paper, all possible metabolic approaches to ischemic heart disease are reviewed and discussed.


2021 ◽  
Vol 8 ◽  
Author(s):  
Min Jiang ◽  
Xiaoye Xie ◽  
Feng Cao ◽  
Yabin Wang

Ischemic heart disease refers to myocardial degeneration, necrosis, and fibrosis caused by coronary artery disease. It can lead to severe left ventricular dysfunction (LVEF ≤ 35–40%) and is a major cause of heart failure (HF). In each contraction, myocardium is subjected to a variety of mechanical forces, such as stretch, afterload, and shear stress, and these mechanical stresses are clinically associated with myocardial remodeling and, eventually, cardiac outcomes. Mitochondria produce 90% of ATP in the heart and participate in metabolic pathways that regulate the balance of glucose and fatty acid oxidative phosphorylation. However, altered energetics and metabolic reprogramming are proved to aggravate HF development and progression by disturbing substrate utilization. This review briefly summarizes the current insights into the adaptations of cardiomyocytes to mechanical stimuli and underlying mechanisms in ischemic heart disease, with focusing on mitochondrial metabolism. We also discuss how mechanical circulatory support (MCS) alters myocardial energy metabolism and affects the detrimental metabolic adaptations of the dysfunctional myocardium.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5480-5480
Author(s):  
Marcus A. Stockschlaeder ◽  
Ali Ghodsizad ◽  
Volker Stoldt ◽  
Ludger Poll ◽  
Ruediger E. Scharf ◽  
...  

Abstract To improve tissue regeneration of ischemic myocardium, autologous bone marrow-derived stem cells have been injected intramyocardially in 10 patients with end-stage ischemic heart disease. Approx. 60 – 380 ml of bone marrow were harvested from the posterior iliac crest and processed in the operating room under GMP conditions using the automated cell selection device CliniMACS. By using the Duesseldorf protocol, the intraoperative isolation of CD133+-stem cells (1.9−10.0 x 106 cells; purity up to 97%) was achieved in less than 3 hours. Following isolation, autologous CD133+-stem cells were injected in a predefined pattern into the myocardium. Cardiac function was assessed by cardiac MRI and echocardiography three, six, and nine months postoperatively. A significant improvement of cardiac function could be documented in 7 out of 10 patients: ejection fraction (EF) before treatment: 10–22% - after 3 months: 18–30% - after 6 months: 19–30%, after 9 months: 21–31%; left ventricular enddiastolic volume (LVEDV) before treatment: 210 ± 123 ml, after 3 months: 169 ± 80 ml, after 6 months: 162 ± 82 ml, after 9 months: 175 ± 70 ml; left ventricular enddiastolic diameter (LVEDD) before treatment: 79.2 ± 7 mm, after 3 months: 57.4 ± 3 mm, after 6 months: 59.4 ± 4 mm, after 9 months: 56.2 ± 5 mm, respectively. In two patients cardiac function improved only temporarily over the first three months, 1 patient died one month after surgery due to a non-cardiac cause. In conclusion, the sole intramyocardial injection of autologous CD133+-cells proved to be safe and led to a significant gain in heart function in 7 of 10 patients, thereby avoiding or postponing (“bridging”) alternative therapies such as heart transplantaton. The benefial effects of intramyocardially injected bone marrow-derived stem cells might be explained by direcct cellular effects including neovascularization and indirect effects including the formation of growth factors promoting tissue repair.


2011 ◽  
Vol 14 (6) ◽  
pp. 384 ◽  
Author(s):  
Vladimir V. Lomivorotov ◽  
Sergey M. Efremov ◽  
Vladimir A. Shmirev ◽  
Dmitry N. Ponomarev ◽  
Vladimir N. Lomivorotov ◽  
...  

<p><b>Background:</b> The aim of the present study was to investigate the cardioprotective effects of the perioperative use of N(2)-L-alanyl-L-glutamine (GLN) in patients with ischemic heart disease (IHD) who undergo their operations under cardiopulmonary bypass (CPB).</p><p><b>Methods:</b> This double-blind, placebo-controlled, randomized study included 50 patients who underwent cardiac surgery with CPB. Exclusion criteria were a left ventricular ejection fraction <50%, diabetes mellitus, <3 months since the onset of myocardial infarction, and emergency surgery. Patients in the study group (n = 25) received 0.4 g/kg GLN (Dipeptiven, 20% solution) per day. Patients in the control group (n = 25) were administered a placebo (0.9% NaCl). The primary end point was the dynamics of troponin I at the following stages: (1) prior to anesthesia, (2) 30 minutes after CPB, (3) 6 hours after CPB, (4) 24 hours after surgery, and (5) 48 hours after surgery. Secondary end points included measurements of hemodynamics with a Swan-Ganz catheter.</p><p><b>Results:</b> On the first postoperative day after the surgery, the median troponin I level was significantly lower in the study group than in the placebo group: 1.280 ng/mL (interquartile range [IQR], 0.840-2.230 ng/mL) versus 2.410 ng/mL (IQR, 1.060-6.600 ng/mL) (<i>P</i> = .035). At 4 hours after cardiopulmonary bypass (CPB), the median cardiac index was higher in the patients in the study group: 2.58 L/min per m<sup>2</sup> (IQR, 2.34-2.91 L/min per m<sup>2</sup>) versus 2.03 L/min per m<sup>2</sup> (IQR, 1.76-2.32 L/min per m<sup>2</sup>) (<i>P</i> = .002). The median stroke index also was higher in the patients who received GLN: 32.8 mL/m<sup>2</sup> (IQR, 27.8-36.0 mL/m<sup>2</sup>) versus 26.1 mL/m<sup>2</sup> (IQR, 22.6-31.8 mL/m<sup>2</sup>) (<i>P</i> = .023). The median systemic vascular resistance index was significantly lower in the study group than in the placebo group: 1942 dyn�s/cm<sup>5</sup> per m<sup>2</sup> (IQR, 1828-2209 dyn�s/cm<sup>5</sup> per m<sup>2</sup>) versus 2456 dyn�s/cm<sup>5</sup> per m<sup>2</sup> (IQR, 2400-3265 dyn�s/cm<sup>5</sup> per m<sup>2</sup>) (<i>P</i> = .001).</p><p><b>Conclusion:</b> Perioperative administration of GLN during the first 24 hours has cardioprotective effects in IHD patients following CPB. This technique enhances the troponin concentration at 24 hours after surgery and is associated with improved myocardial function.</p>


2017 ◽  
pp. 89-94
Author(s):  
Ke Toan Tran ◽  
Thi Thuy Hang Nguyen

Objective: To determine pulmonary vascular resistance (PVR) by echocardiography - Doppler and to find correlation between pulmonary vascular resistance with left ventricular EF, PAPs, TAPSE, tissue S-wave of the tricuspid valve in patients with ischemic heart disease. Subjects and Methods: We studied on 82 patients with ischemic heart disease and EF<40% including 36 females, 46 males. Patients were estimated for pulmonary vascular resistance, EF, PAPs, TAPSE, tissue S-wave of the tricuspid valve by echocardiographyDoppler. Results: 64.6% of patients are increased PVR, average of PVR is 3.91 ± 1.85 Wood units and it is increasing with NYHA severity. There are negative correlations between pulmonary vascular resistance with left ventricular ejection fraction (r = - 0.545; p <0.001), TAPSE index (r= -0.590; p <0.001) and tissue S-wave of the tricuspid valve (r = -0.420; p <0.001); positive correlation with systolic pulmonary artery pressure (r = 0.361, p = 0.001), Conclusions: Increased PVR is the primary mechanism for pulmonary hypertension and right heart failure in patients with left heart disease. Determination of PVR in patients with left ventricular dysfunction by echocardiography is important in clinical practice. Key words: Echocardiography-Doppler; Pulmonary vascular resistance; ischemic heart disease


2021 ◽  
Vol 10 (11) ◽  
pp. 2284
Author(s):  
Diana Gurzău ◽  
Alexandra Dădârlat-Pop ◽  
Bogdan Caloian ◽  
Gabriel Cismaru ◽  
Horaţiu Comşa ◽  
...  

Left bundle branch block is not a benign pathology, and its presence requires the identification of a pathological substrate, such as ischemic heart disease. Left bundle branch block appears to be more commonly associated with normal coronary arteries, especially in women. The objectives of our study were to describe the particularities of left bundle branch block in women compared to men with ischemic heart disease. Result: We included seventy patients with left bundle branch block and ischemic heart disease, with a mean age of 67.01 ± 8.89 years. There were no differences in the profile of risk factors, except for smoking and uric acid. The ventricular depolarization (QRS) duration was longer in men than women (136.86 ± 8.32 vs. 132.57 ± 9.19 msec; p = 0.018) and also men were observed to have larger left ventricular diameters. Left bundle branch block duration was directly associated with ventricular diameters and indirectly associated with left ventricular ejection fraction value, especially in women (R = −0.52, p = 0.0012 vs. R = −0.50, p = 0.002). In angiography, 80% of women had normal epicardial arteries compared with 65.7% of men; all these patients presented with microvascular dysfunction. Conclusion: The differences between the sexes were not so obvious in terms of the presence of risk factors; instead, there were differences in electrocardiographic, echocardiographic, and angiographic aspects. Left bundle branch block appears to be a marker of microvascular angina and systolic dysfunction, especially in women.


2021 ◽  
Vol 77 (18) ◽  
pp. 2581
Author(s):  
Andrea Teira Calderon ◽  
Adrián Margarida ◽  
Ignacio Santiago ◽  
Indira Cabrera ◽  
Sofia Gonzalez Lizarbe ◽  
...  

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