scholarly journals β-Hydroxybutyrate Exacerbates Hypoxic Injury by Inhibiting HIF-1α-Dependent Glycolysis in Cardiomyocytes—Adding Fuel to the Fire?

2021 ◽  
Author(s):  
Xiurui Ma ◽  
Zhen Dong ◽  
Jingyi Liu ◽  
Leilei Ma ◽  
Xiaolei Sun ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Ketone Body ◽  
Human Peripheral Blood ◽  
Left Ventricular ◽  
Cell Counting ◽  
Left Ventricular Ejection ◽  
Chow Diet ◽  
Dead Cell ◽  
Hypoxic Conditions

Abstract Purpose Ketone body oxidation yields more ATP per mole of consumed oxygen than glucose. However, whether an increased ketone body supply in hypoxic cardiomyocytes and ischemic hearts is protective or not remains elusive. The goal of this study is to determine the effect of β-hydroxybutyrate (β-OHB), the main constituent of ketone bodies, on cardiomyocytes under hypoxic conditions and the effects of ketogenic diet (KD) on cardiac function in a myocardial infarction (MI) mouse model. Methods Human peripheral blood collected from patients with acute myocardial infarction and healthy volunteers was used to detect the level of β-OHB. N-terminal proB-type natriuretic peptide (NT-proBNP) levels and left ventricular ejection fractions (LVEFs) were measured to study the relationship between plasma β-OHB and cardiac function. Adult mouse cardiomyocytes and MI mouse models fed a KD were used to research the effect of β-OHB on cardiac damage. qPCR, western blot analysis, and immunofluorescence were used to detect the interaction between β-OHB and glycolysis. Live/dead cell staining and imaging, lactate dehydrogenase, Cell Counting Kit-8 assays, echocardiography, and 2,3,5-triphenyltetrazolium chloride staining were performed to evaluate the cardiomyocyte death, cardiac function, and infarct sizes. Results β-OHB level was significantly higher in acute MI patients and MI mice. Treatment with β-OHB exacerbated cardiomyocyte death and decreased glucose absorption and glycolysis under hypoxic conditions. These effects were partially ameliorated by inhibiting hypoxia-inducible factor 1α (HIF-1α) degradation via roxadustat administration in hypoxia-stimulated cardiomyocytes. Furthermore, β-OHB metabolisms were obscured in cardiomyocytes under hypoxic conditions. Additionally, MI mice fed a KD exhibited exacerbated cardiac dysfunction compared with control chow diet (CD)-fed MI mice. Conclusion Elevated β-OHB levels may be maladaptive to the heart under hypoxic/ischemic conditions. Administration of roxadustat can partially reverse these harmful effects by stabilizing HIF-1α and inducing a metabolic shift toward glycolysis for energy production.

scholarly journals β-Hydroxybutyrate Exacerbates Hypoxic Injury by Inhibiting HIF-1α-Dependent Glycolysis in Cardiomyocytes—Adding Fuel to the Fire?

2021 ◽  
Author(s):  
Xiurui Ma ◽  
Zhen Dong ◽  
jingyi Liu ◽  
Leilei Ma ◽  
Xiaolei Sun ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Hypoxia Inducible Factor ◽  
Cell Counting ◽  
Chow Diet ◽  
Dead Cell ◽  
Triphenyltetrazolium Chloride ◽  
Cardiac Damage ◽  
Hypoxic Conditions

Abstract Purpose: Ketone body oxidation yields more ATP per mole of consumed oxygen than glucose. However, whether an increased ketone body supply in hypoxic cardiomyocytes and ischemic hearts is protective or not remains elusive. The goal of this study is to determine the effect of β-hydroxybutyrate (β-OHB), the main constituent of ketone bodies, on cardiomyocytes under hypoxic conditions and the effects of ketogenic diet (KD) on cardiac function in a myocardial infarction (MI) mouse model. Methods: Adult mouse cardiomyocytes and MI mouse models fed a KD were used to research the effect of β-OHB on cardiac damage. qPCR, western blot analysis and immunofluorescence were used to detect the interaction between β-OHB and glycolysis. Live/dead cell staining and imaging, lactate dehydrogenase, Cell Counting Kit-8 assays, echocardiography and 2,3,5-triphenyltetrazolium chloride staining were performed to evaluate the cardiomyocyte death, cardiac function and infarct sizes. Results: β-OHB level was significantly higher in acute MI patients and MI mice. Treatment with β-OHB exacerbated cardiomyocyte death and decreased glucose absorption and glycolysis under hypoxic conditions. These effects were partially ameliorated by inhibiting hypoxia-inducible factor 1α (HIF-1α) degradation via roxadustat administration in hypoxia-stimulated cardiomyocytes. Furthermore, β-OHB metabolisms were obscured in cardiomyocytes under hypoxic conditions. Additionally, MI mice fed a KD exhibited exacerbated cardiac dysfunction compared with control chow diet (CD)-fed MI mice. Conclusion: Elevated β-OHB levels may be maladaptive to the heart under hypoxic/ischemic conditions. Administration of roxadustat can partially reverse these harmful effects by stabilizing HIF-1α and inducing a metabolic shift toward glycolysis for energy production.

Inhibition of pro-inflammatory myeloid cell responses by short-term S100A9 blockade improves cardiac function after myocardial infarction

2019 ◽  
Vol 40 (32) ◽  
pp. 2713-2723 ◽  
Author(s):  
Goran Marinković ◽  
Helena Grauen Larsen ◽  
Troels Yndigegn ◽  
Istvan Adorjan Szabo ◽  
Razvan Gheorghita Mares ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Immune Response ◽  
Cardiac Function ◽  
Myeloid Cell ◽  
Left Ventricular ◽  
Haematopoietic Stem Cell ◽  
Left Ventricular Ejection ◽  
Coronary Artery Ligation ◽  
Short Term ◽  
Coronary Syndrome

Abstract Aims Neutrophils have both detrimental and beneficial effects in myocardial infarction (MI), but little is known about the underlying pathways. S100A8/A9 is a pro-inflammatory alarmin abundantly expressed in neutrophils that is rapidly released in the myocardium and circulation after myocardial ischaemia. We investigated the role of S100A8/A9 in the innate immune response to MI. Methods and results In 524 patients with acute coronary syndrome (ACS), we found that high plasma S100A8/A9 at the time of the acute event was associated with lower left ventricular ejection fraction (EF) at 1-year and increased hospitalization for heart failure (HF) during follow-up. In wild-type C57BL/6 mice with MI induced by permanent coronary artery ligation, treatment with the S100A9 blocker ABR-238901 during the inflammatory phase of the immune response inhibited haematopoietic stem cell proliferation and myeloid cell egression from the bone marrow. The treatment reduced the numbers of neutrophils and monocytes/macrophages in the myocardium, promoted an anti-inflammatory environment, and significantly improved cardiac function compared with MI controls. To mimic the clinical scenario, we further confirmed the effects of the treatment in a mouse model of ischaemia/reperfusion. Compared with untreated mice, 3-day ABR-238901 treatment significantly improved left ventricular EF (48% vs. 35%, P = 0.002) and cardiac output (15.7 vs. 11.1 mL/min, P = 0.002) by Day 21 post-MI. Conclusion Short-term S100A9 blockade inhibits inflammation and improves cardiac function in murine models of MI. As an excessive S100A8/A9 release is linked to incident HF, S100A9 blockade might represent a feasible strategy to improve prognosis in ACS patients.

scholarly journals Association of ADAMTS-7 Levels with Cardiac Function in a Rat Model of Acute Myocardial Infarction

2016 ◽  
Vol 38 (3) ◽  
pp. 950-958 ◽  
Author(s):  
Wenjing Wu ◽  
Hui Wang ◽  
Changan Yu ◽  
Jiahui Li ◽  
Yanxiang Gao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Cardiac Function ◽  
Matrix Protein ◽  
Ventricular Remodeling ◽  
Structural Parameters ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Post Surgery

Background/Aims: High ADAMTS-7 levels are associated with acute myocardial infarction (AMI), although its involvement in ventricular remodeling is unclear. In this study, we investigated the association between ADAMTS-7 expression and cardiac function in a rat AMI model. Methods: Sprague-Dawley rats were randomized into AMI (n = 40) and sham (n = 20) groups. The left anterior descending artery was sutured to model AMI. Before surgery and 7, 14, 28, and 42 days post-surgery, ADAMTS-7 and brain natriuretic peptide (BNP), and cartilage oligomeric matrix protein (COMP) were assessed by ELISA, western blot, real-time RT-PCR, and/or immunohistochemistry. Cardiac functional and structural parameters were assessed by M-mode echocardiography. Results: After AMI, plasma ADAMTS-7 levels increased, peaking on day 28 (AMI: 13.2 ± 6.3 vs. sham: 3.4 ± 1.3 ng/ml, P < 0.05). Compared with the sham group, ADAMTS-7 expression was higher in the infarct zone at day 28. COMP present in normal myocardium was degraded by day 28 post-AMI. Plasma ADAMTS-7 correlated positively with BNP (r = 0.642, P = 0.025), left ventricular end-diastolic diameter (r = 0.695, P = 0.041), left ventricular end-systolic diameter (r = 0.710, P = 0.039), left ventricular ejection fraction (r = 0.695, P = 0.036), and left ventricular short-axis fractional shortening (r = 0.721, P = 0.024). Conclusions: ADAMTS-7 levels may reflect the degree of ventricular remodeling after AMI.

scholarly journals Hypoxic-conditioned cardiosphere-derived cell sheet transplantation for chronic myocardial infarction

2019 ◽  
Vol 56 (6) ◽  
pp. 1062-1074
Author(s):  
Akira Fujita ◽  
Koji Ueno ◽  
Toshiro Saito ◽  
Masashi Yanagihara ◽  
Hiroshi Kurazumi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Cell Sheet ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Chronic Myocardial Infarction ◽  
Ventricular Ejection Fraction ◽  
Paracrine Effects

Abstract OBJECTIVES Cell therapy provides a suitable environment for regeneration through paracrine effects such as secretion of growth factors. Cardiosphere-derived cells (CDCs) have a high capacity for growth factor secretion and are an attractive target for clinical applications. In particular, a cell sheet technique was reported to have clinical advantages by covering a specific region. Here, we examined the effect of the hypoxic-conditioned (HC) autologous CDC sheet therapy on a rabbit chronic myocardial infarction model. METHODS CDC sheet function was assessed by the enzyme-linked immunosorbent assay and quantified by polymerase chain reaction in vitro (days 1–3 of conditioning). The rabbit chronic myocardial infarction model was established by left coronary ligation. Autologous CDCs were isolated from the left atrial specimen; CDC sheets with or without 2-day HC were transplanted onto the infarcted hearts at 4 weeks. The cardiac function was assessed by an echocardiography at 0, 4 and 8 weeks. A histological analysis of the host hearts was performed by tomato lectin staining at 8 weeks. RESULTS The optimal HC duration was 48 h. HC significantly increased the mRNA expression levels of VEGF and ANG2 on day 2 compared to the normoxic-conditioned (NC) group. The HC group showed significant improvement in the left ventricular ejection fraction (64.4% vs 58.8% and 53.4% in the NC and control) and a greater lectin-positive area in the ischaemic region (HC:NC:control = 13:8:2). CONCLUSIONS HC enhances the paracrine effect of a CDC sheet on angiogenesis to improve cardiac function in the chronic myocardial infarction model, which is essential for cardiomyocyte proliferation during cardiac regeneration.

scholarly journals Sustained subcutaneous delivery of secretome of human cardiac stem cells promotes cardiac repair following myocardial infarction

2020 ◽  
Author(s):  
Andrew R Kompa ◽  
David W Greening ◽  
Anne M Kong ◽  
Paul J McMillan ◽  
Haoyun Fang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Cardiac Function ◽  
Extracellular Vesicles ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cardiac Stem Cells ◽  
Subcutaneous Implantation ◽  
Ventricular Ejection Fraction ◽  
Post Implantation

Abstract Aims To establish pre-clinical proof of concept that sustained subcutaneous delivery of the secretome of human cardiac stem cells (CSCs) can be achieved in vivo to produce significant cardioreparative outcomes in the setting of myocardial infarction. Methods and results Rats were subjected to permanent ligation of left anterior descending coronary artery and randomized to receive subcutaneous implantation of TheraCyte devices containing either culture media as control or 1 × 106 human W8B2+ CSCs, immediately following myocardial ischaemia. At 4 weeks following myocardial infarction, rats treated with W8B2+ CSCs encapsulated within the TheraCyte device showed preserved left ventricular ejection fraction. The preservation of cardiac function was accompanied by reduced fibrotic scar tissue, interstitial fibrosis, cardiomyocyte hypertrophy, as well as increased myocardial vascular density. Histological analysis of the TheraCyte devices harvested at 4 weeks post-implantation demonstrated survival of human W8B2+ CSCs within the devices, and the outer membrane was highly vascularized by host blood vessels. Using CSCs expressing plasma membrane reporters, extracellular vesicles of W8B2+ CSCs were found to be transferred to the heart and other organs at 4 weeks post-implantation. Furthermore, mass spectrometry-based proteomic profiling of extracellular vesicles of W8B2+ CSCs identified proteins implicated in inflammation, immunoregulation, cell survival, angiogenesis, as well as tissue remodelling and fibrosis that could mediate the cardioreparative effects of secretome of human W8B2+ CSCs. Conclusions Subcutaneous implantation of TheraCyte devices encapsulating human W8B2+ CSCs attenuated adverse cardiac remodelling and preserved cardiac function following myocardial infarction. The TheraCyte device can be employed to deliver stem cells in a minimally invasive manner for effective secretome-based cardiac therapy.

scholarly journals Thyroid hormone and recovery of cardiac function in patients with acute myocardial infarction: a strong association?

2011 ◽  
Vol 165 (1) ◽  
pp. 107-114 ◽  
Author(s):  
Ioannis Lymvaios ◽  
Iordanis Mourouzis ◽  
Dennis V Cokkinos ◽  
Meletios A Dimopoulos ◽  
Savvas T Toumanidis ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Thyroid Hormone ◽  
Cardiac Function ◽  
Experimental Studies ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Early Reperfusion ◽  
Ventricular Ejection Fraction ◽  
Potential Implication

ObjectiveThis study investigated whether changes in thyroid hormone (TH) in plasma are associated with the recovery of cardiac function in patients with acute myocardial infarction (AMI). Previous experimental studies have provided evidence of potential implication of TH signaling in post-ischemic recovery of cardiac function.MethodsA total of 47 patients with AMI and early reperfusion therapy were included in this study. Myocardial injury was analyzed by peak creatinine kinase–MB (CKMB) and cardiac function was assessed by echocardiographic left ventricular ejection fraction (LVEF%). Recovery of function (ΔEF%) was estimated as the difference of LVEF% between 48 h and 6 months (6 mo) after AMI. Total triiodothyronine (T3), thyroxine (T4), and TSH were measured in plasma at different time points (24 h, 48 h, 5 d, and 6 mo).ResultsA significant correlation between LVEF% and T3 (r=0.5, P=0.0004) was found early after AMI (48 h), whereas no correlation was observed between CKMB and T3 (r=−0.04, P=0.81). A strong correlation was found between ΔEF% and total T3 (r=0.64, P=10−6) at 6 mo after AMI. Furthermore, multivariate regression analysis revealed that T3 at 6 mo (r=0.64, r2=0.41, P=10−6) was an independent determinant of ΔEF%.ConclusionChanges in T3 levels in plasma are closely correlated with the early and late recovery of cardiac function after AMI. T3 levels at 6 mo appear to be an independent predictor of late functional recovery.

Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure

2011 ◽  
Vol 301 (2) ◽  
pp. H459-H468 ◽  
Author(s):  
Meimei Yin ◽  
Iwan C. C. van der Horst ◽  
Joost P. van Melle ◽  
Cheng Qian ◽  
Wiek H. van Gilst ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Function ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Oral Glucose ◽  
Mrna Levels ◽  
Ventricular Ejection Fraction ◽  
Glucose Levels ◽  
First Choice

Metformin is the first choice drug for the treatment of patients with diabetes, but its use is debated in patients with advanced cardiorenal disease. Epidemiological data suggest that metformin may reduce cardiac events, in patients both with and without heart failure. Experimental evidence suggests that metformin reduces cardiac ischemia-reperfusion injury. It is unknown whether metformin improves cardiac function (remodeling) in a long-term post-MI remodeling model. We therefore studied male, nondiabetic, Sprague-Dawley rats that were subjected to either myocardial infarction (MI) or sham operation. Animals were randomly allocated to treatment with normal water or metformin-containing water (250 mg·kg−1·day−1). At baseline, 6 wk, and 12 wk, metabolic parameters were analyzed and oral glucose tolerance tests (OGTT) were performed. Echocardiography and hemodynamic parameters were assessed 12 wk after MI. In the MI model, infarct size was significantly smaller after 12-wk metformin treatment (29.6 ± 3.2 vs. 38.0 ± 2.2%, P < 0.05). Moreover, metformin resulted in less left ventricular dilatation (6.0 ± 0.4 vs. 7.6 ± 0.6 mm, P < 0.05) and preservation of left ventricular ejection fraction (65.8 ± 3.7% vs. 48.6 ± 5.6%, P < 0.05) compared with MI control. The improved cardiac function was associated with decreased atrial natriuretic peptide mRNA levels in the metformin-treated group (50% reduction compared with MI, P < 0.05). Insulin resistance did not occur during cardiac remodeling (as indicated by normal OGTT) and fasting glucose levels and the pattern of the OGTT were not affected by metformin. Molecular analyses suggested that altered AMP kinase phosphorylation status and low insulin levels mediate the salutary effects of metformin. Altogether our results indicate that metformin may have potential to attenuate heart failure development after myocardial infarction, in the absence of diabetes and independent of systemic glucose levels.

P5397Mesenchymal stem cells derived from bone marrow promotes cardiomyocytes survival under hypoxia through exosomal miR-210

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Cheng ◽  
X Y Song ◽  
L Chen ◽  
R D Xu ◽  
Q Qin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Cardiac Function ◽  
Conditioned Medium ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Ventricular Ejection Fraction ◽  
Paracrine Effect

Abstract Mesenchymal stem cells derived from bone marrow promotes cardiomyocytes survival under hypoxia through exosomal miR-210 Background A paracrine effect was regarded as the key mechanism involved in the MSC (mesenchymal stem cell)-based treatment for myocardial infarction. In our pilot experiments, hypoxia remarkably promotes MSC to paracrine exosomal miR-210, which could significantly enhance the cardiomyocytes survival in hypoxic incubation, suggesting that exosomal miR-210 played critical roles in the favorable paracrine effect of MSC on cardiomyocytes. Purpose The aim of this study was to investigate the important mechanism by which MSCs promote the tolerance of cardiomyocytes to hypoxia by secreting exosomal miR-210. Methods and results The exosomes were isolated from MSCs conditioned medium through ultracentrifugation, and we detected that miR-210 was the most abundant in MSC-exosome and increased most prominently in the hypoxia. The extracted exosomes were prepared for conditioned medium and the effect on myocardial protection was examined. The viability of control group was much better than the cardiomyocytes treated with hypoxia, but it was further increased in the presence of MSC-exosome, however, measurement was significantly lower in cardiomyocytes in hypoxia with exosomes derived from MSCs treated with GW4869. Subsequently, the co-localization of miR-210 with exosome-specific surface markers CD81 and CD63 were observed by immunofluorescence technique. Continuous magnetic live cell imaging was used to observe the uptake of exosome by cardiomyocytes, and fluorescence localization was used to observe the localization of miR-210 with Cy3 fluorescence in cardiomyocytes. Then, we demonstrated that MSCs exosomal miR-210 exerts the cardioprotective effect by regulating the AIFM3 (apoptosis-inducing factor mitochondria-associated protein 3), and we directly overexpressed miRNA-210 in cardiomyocytes and the results showed that the regulatory activity of the intake of exosomal miR-210 was consistent with that of the biological exosomal miR-210. Finally, we verified the protective effect on the ischemic myocardium by constructing rat myocardial infarction models. The level of apoptosis was detected at 1 week after myocardial infarction. The left ventricular ejection fraction and ventricular remodeling were measured at 4 weeks. In vivo, we demonstrated that explanted miR-210 from transplanted MSCs significantly reduced myocardial necrosis and apoptosis induced by ischemia and improved cardiac function and myocardial remodeling. Conclusion Here, we show that the exosomal miR-210 secreted by MSCs significantly increase the viability of cardiomyocytes and cardiac function. These findings suggest that exosomal miR-210 is a key effector that mediates the protection against hypoxia. Acknowledgement/Funding National Natural Science Foundation of China (Grant Nos. 81470467)

scholarly journals Traditional Formula, Modern Application: Chinese Medicine Formula Sini Tang Improves Early Ventricular Remodeling and Cardiac Function after Myocardial Infarction in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Jiangang Liu ◽  
Karoline Peter ◽  
Dazhuo Shi ◽  
Lei Zhang ◽  
Guoju Dong ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Chinese Medicine ◽  
Cardiac Function ◽  
Ventricular Remodeling ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Left Ventricular Cavity ◽  
Myocardial Tissue ◽  
Type I ◽  
Chinese Medicine Formula

Sini Tang (SNT) is a traditional Chinese herbal formula consisting of four different herbs: the root ofAconitum carmichaelii, the bark ofCinnamomum cassia, the rhizome ofZingiber officinale, and the root ofGlycyrrhiza uralensis. This study aims to evaluate the improvement of early ventricular remodeling and cardiac function in myocardial infarction (MI) rats by SNT. A MI model was established by ligation of the left anterior descending coronary artery. Following treatment for 4 weeks, ultrasonic echocardiography was performed. Myocardial histopathological changes were observed using haematoxylin and eosin staining. Collagens (type I and type III), transforming growth factor-β1 (TGF-β1), and Toll-like receptors (TLR-2 and TLR-4) were measured in plasma, serum, and myocardial tissue. SNT treatment decreased the infarct size, the left ventricular cavity area/heart cavity area ratio, and the left ventricle dimension at end systole and increased the left ventricular ejection fraction. SNT reduced the levels of TLR-2 and TLR-4 in myocardial tissue significantly and decreased the collagens content in serum and in myocardial tissue. SNT could partially reduce the level of TGF-β1 in serum and in myocardial tissue. Our data suggest that the Chinese medicine formula SNT has the potential to improve early ventricular remodeling and cardiac function after MI.

scholarly journals Recovery of Infarcted Myocardium in an In Vivo Experiment

Medicina ◽  
2011 ◽  
Vol 47 (11) ◽  
pp. 88 ◽  
Author(s):  
Raimondas Širmenis ◽  
Antanas Kraniauskas ◽  
Rasa Jarašienė ◽  
Daiva Baltriukienė ◽  
Audronė Kalvelytė ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Cardiac Function ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Infarcted Myocardium ◽  
Myogenic Stem Cells

Acute myocardial infarction leads to the loss of functional cardiomyocytes and structural integrity. The adult heart cannot repair the damaged tissue due to inability of mature cardiomyocytes to divide and lack of stem cells. The aim of this study was to evaluate the efficiency of introduced autologous skeletal musclederived stem cells to recover the function of acutely infarcted rabbit heart in the early postoperative period. Material and Methods. As a model for myocardium restoration in vivo, experimental rabbit heart infarct was used. Autologic adult myogenic stem cells were isolated from skeletal muscle and propagated in culture. Before transplantation, the cells were labeled with 4´,6-diamidino-2-phenylindole and then, during heart surgery, introduced into the rabbit acutely infarcted myocardium. Postoperative cardiac function was monitored by recording electrocardiograms and echocardiograms. At the end of the experiment, the efficiency of cell integration was evaluated histologically. Results. Rabbit cardiac function recovered after 1 month after the induction of experimental infarction both in the control and experimental groups. Therefore, the first month after the infarction was the most significant for the assessment of cell transplantation efficacy. Transplanted cell integration into infarcted myocardium was time- and individual-dependent. Evaluation of changes in left ventricular ejection fraction after the induction of myocardial infarction revealed better recovery in the experimental group; however, the difference among animals in the experimental and control groups varied and was not significant. Conclusions. Autologous myogenic stem cells repopulated infarcted myocardium with different efficiency in each individual. This variability may account for the observed difference in postoperative cardiac recovery in a rabbit model.

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