scholarly journals Bioenergetic and Functional Consequences of Bone Marrow–Derived Multipotent Progenitor Cell Transplantation in Hearts With Postinfarction Left Ventricular Remodeling

Circulation ◽  
2007 ◽  
Vol 115 (14) ◽  
pp. 1866-1875 ◽  
Author(s):  
Lepeng Zeng ◽  
Qingsong Hu ◽  
Xiaohong Wang ◽  
Abdul Mansoor ◽  
Joseph Lee ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ejection Fraction ◽  
Cell Transplantation ◽  
Cyclosporine A ◽  
Artery Occlusion ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Infarct Zone ◽  
Ventricular Ejection Fraction ◽  
Left Anterior Descending Artery

Background— The present study examined whether transplantation of adherent bone marrow–derived stem cells, termed pMultistem, induces neovascularization and cardiomyocyte regeneration that stabilizes bioenergetic and contractile function in the infarct zone and border zone (BZ) after coronary artery occlusion. Methods and Results— Permanent left anterior descending artery occlusion in swine caused left ventricular remodeling with a decrease of ejection fraction from 55±5.6% to 30±5.4% (magnetic resonance imaging). Four weeks after left anterior descending artery occlusion, BZ myocardium demonstrated profound bioenergetic abnormalities, with a marked decrease in subendocardial phosphocreatine/ATP ( 31 P magnetic resonance spectroscopy; 1.06±0.30 in infarcted hearts [n=9] versus 1.90±0.15 in normal hearts [n=8; P <0.01]). This abnormality was significantly improved by transplantation of allogeneic pMultistem cells (subendocardial phosphocreatine/ATP to 1.34±0.29; n=7; P <0.05). The BZ protein expression of creatine kinase–mt and creatine kinase–m isoforms was significantly reduced in infarcted hearts but recovered significantly in response to cell transplantation. MRI demonstrated that the infarct zone systolic thickening fraction improved significantly from systolic “bulging” in untreated animals with myocardial infarction to active thickening (19.7±9.8%, P <0.01), whereas the left ventricular ejection fraction improved to 42.0±6.5% ( P <0.05 versus myocardial infarction). Only 0.35±0.05% donor cells could be detected 4 weeks after left anterior descending artery ligation, independent of cell transplantation with or without immunosuppression with cyclosporine A (with cyclosporine A, n=6; no cyclosporine A, n=7). The fraction of grafted cells that acquired an endothelial or cardiomyocyte phenotype was 3% and ≈2%, respectively. Patchy spared myocytes in the infarct zone were found only in pMultistem transplanted hearts. Vascular density was significantly higher in both BZ and infarct zone of cell-treated hearts than in untreated myocardial infarction hearts ( P <0.05). Conclusions— Thus, allogeneic pMultistem improved BZ energetics, regional contractile performance, and global left ventricular ejection fraction. These improvements may have resulted from paracrine effects that include increased vascular density in the BZ and spared myocytes in the infarct zone.

Implication of anti-angiogenic VEGF-A165b in angiogenesis and systolic function after reperfused myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Marcos Garces ◽  
C Rios-Navarro ◽  
L Hueso ◽  
A Diaz ◽  
C Bonanad ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Adjuvant Therapy ◽  
Ejection Fraction ◽  
Infarct Size ◽  
Systolic Function ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Coronary Reperfusion ◽  
Ventricular Ejection Fraction

Abstract Background Angiogenesis participates in re-establishing microcirculation after myocardial infarction (MI). Purpose In this study, we aim to further understand the role of the anti-angiogenic isoform vascular endothelial growth factor (VEGF)-A165b after MI and explore its potential as a co-adjuvant therapy to coronary reperfusion. Methods Two mice MI models were formed: 1) permanent coronary ligation (non-reperfused MI), 2) transient 45-min coronary occlusion followed by reperfusion (reperfused MI); in both models, animals underwent echocardiography before euthanasia at day 21 after MI induction. Serum and myocardial VEGF-A165b levels were determined. In both experimental MI models, functional and structural implication of VEGF-A165b blockade was assessed. In a cohort of 104 ST-segment elevation MI patients, circulating VEGF-A165b levels were correlated with cardiovascular magnetic resonance-derived left ventricular ejection fraction at 6-months and with the occurrence of adverse events (death, heart failure and/or re-infarction). Results In both models, circulating and myocardial VEGF-A165b presence was increased 21 days after MI induction. Serum VEGF-A165b levels inversely correlated with systolic function evaluated by echocardiography. VEGF-A165b blockage increased capillary density, reduced infarct size, and enhanced left ventricular function in reperfused, but not in non-reperfused MI experiments. In patients, higher VEGF-A165b levels correlated with depressed ejection fraction and worse outcomes. Conclusions In experimental and clinical studies, higher serum VEGF-A165b levels associates with a worse systolic function. Its blockage enhances neoangiogenesis, reduces infarct size, and increases ejection fraction in reperfused, but not in non-reperfused MI experiments. Therefore, VEGF-A165b neutralization represents a potential co-adjuvant therapy to coronary reperfusion. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was funded by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (Exp. PIE15/00013, PI17/01836, PI18/00209 and CIBERCV16/11/00486).

scholarly journals Genetic and nongenetic factors in assessing the prognosis of patients after myocardial infarction with high medical adherence

2021 ◽  
Vol 20 (4) ◽  
pp. 2773
Author(s):  
K. G. Pereverzeva ◽  
S. S. Yakushin ◽  
A. S. Galus ◽  
A. R. Shanina
Keyword(s):  
Myocardial Infarction ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Composite Endpoint ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Medical Adherence ◽  
Ventricular Ejection Fraction ◽  
Q Wave

Aim. During one-year follow-up, to assess the effect of genetic and nongenetic factors on the risk of poor outcomes in patients after myocardial infarction (MI) with high medical adherence.Material and methods. The study included 250 patients admitted to the hospital due to MI in the period from September 1, 2018 to May 1, 2019 and with a potentially high medical adherence. Twelve months after MI, patients were assessed for adherence to therapy and the effect of genetic and nongenetic factors on the patient prognosis.Results. Within 12 months after MI, 70 (28,0%) patients had a composite endpoint: all-cause death, MI, cerebral stroke, and nonelective coronary revascularization. There were following factors increasing the risk of composite endpoint: non-Q-wave MI (relative risk (RR), 2,63; 95% confidence interval (CI): 1,63-4,25 (p=0,001); left ventricular ejection fraction ≤35% — RR, 2,03; 95% CI: 1,17-3,50 (p<0,0001); CYP2C19 GA/AA genotype (RR, 1,58; 95% CI: 1,06-2,37 (p<0,00001)).Conclusion. The study results allow identifying patients with a high risk of poor outcome: patients with non-Q-wave MI, left ventricular ejection fraction ≤35%, and CYP2C19 GA/AA genotype.

scholarly journals Is Skeletal Myoblast Transplantation Clinically Relevant in the Era of Angiotensin-Converting Enzyme Inhibitors?

Circulation ◽  
2001 ◽  
Vol 104 (suppl_1) ◽  
Author(s):  
Bruno Pouzet ◽  
Saïd Ghostine ◽  
Jean-Thomas Vilquin ◽  
Isabelle Garcin ◽  
Marcio Scorsin ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Cell Transplantation ◽  
Ace Inhibitors ◽  
Culture Medium ◽  
Ace Inhibitor ◽  
Ex Vivo ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Coronary Artery Ligation ◽  
Ventricular Ejection Fraction

Background There is compelling experimental evidence that autologous skeletal muscle (SM) cell transplantation improves postinfarction cardiac function. This study assessed whether this benefit is still manifested in the clinically relevant setting of a treatment by ACE inhibitors. Methods and Results A myocardial infarction was created in 99 rats by coronary artery ligation. They were divided into 4 groups. Two groups did not receive any drug and were intramyocardially injected 7 days after the infarct with either culture medium alone (control rats, n=16) or autologous SM cells (2.3×10 6 myoblasts) previously expanded ex vivo for 7 days (myoblasts, n=24). Two other groups received the ACE inhibitor perindoprilat (1 mg · kg −1 · d −1 ), started the day of the infarct and continued uninterruptedly thereafter, and underwent time-matched procedures, that is, they were intramyocardially injected at 7 days after infarction with either culture medium alone (ACE inhibitors, n=22) or autologous SM cells (2.5×10 6 myoblasts) previously expanded ex vivo for 7 days (ACE inhibitors+myoblasts, n=37). Left ventricular function was assessed by 2D echocardiography. At the end of the 2-month study, left ventricular ejection fraction (%, mean±SEM) was increased in all groups (myoblasts, 37.4±1.2; ACE inhibitors, 31.6±1.7; ACE inhibitors+myoblasts, 43.9±1.4) compared with that in control rats (19.8±0.7) ( P <0.0001). The improvement in ejection fraction was similar in the ACE inhibitor and the myoblast groups (31.6±1.7 versus 37.4±1.2, P =0.0636). However, in the ACE inhibitor+myoblast group, this improvement was greater than that seen in hearts receiving either treatment alone (43.9±1.4 versus 31.6±1.7 in the ACE inhibitor group and 43.9±1.4. versus 37.4±1.2 in the myoblast group, P <0.0001 and P =0.0084, respectively). Conclusions These data provide further support for the clinical relevance of autologous SM cell transplantation in that its cardioprotective effects are additive to those observed with ACE inhibitors.

scholarly journals Indicators of the left ventricular-arterial coupling interaction in chronic forms of ischemic heart disease: relationships of the protradenomedullin and N-terminal probrain natriuretic peptide

Kardiologiia ◽  
2019 ◽  
Vol 59 (6S) ◽  
pp. 41-50
Author(s):  
E. I. Myasoedova ◽  
L. P. Voronina ◽  
O. S. Polunina ◽  
Yu. G. Shvarts
Keyword(s):  
Myocardial Infarction ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Ischemic Cardiomyopathy ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Coupling Interaction ◽  
Left Ventricular Arterial Coupling

Purpose of the study. Analyze the parameters of the interaction between the left ventricle and the arterial system in patients with chronic forms of coronary heart disease and to identify relationships with levels of proadrenomedullin (MR‑proADM) and N‑terminal precursor of the brain natriuretic peptide B (NT‑proBNP).Materials and methods.240 patients with chronic forms of coronary heart disease (median – 55,9 [43; 63] years) and Q‑forming myocardial infarction in the past were examined. Of these, 110 patients with myocardial infarction and preserved lef ventricular ejection fraction and 130 patients with ischemic cardiomyopathy. All patients were calculated parameters of lef ventricular‑arterial interaction and the determination in blood serum levels of MR‑proADM and NT‑proBNP.Results.In patients with ischemic cardiomyopathy, an increase in the lef ventricular‑arterial interaction index was detected (2,51 [1,18; 5,00]), which reflects a decrease in the functional abilities and efficiency of the heart. In patients with myocardial infarction and a preserved left ventricular ejection fraction, this indicator was in the range of normal values (0,78 [0,55; 1,07]), which indicates an effective cardiac work. A study of MR‑proADM and NT‑proBNP levels demonstrated an increase in both groups (1,72 [1,56; 1,98] nmol/l and 779,3 [473; 2193] pg/ml in the group of patients with ischemic cardiomyopathy; 0,89 [0,51; 1,35] nmol/l and 246 [118; 430] pg/ml in the group of patients with myocardial infarction and preserved left ventricular ejection fraction), and the correlation analysis with left ventricular‑arterial coupling interaction parameters allowed identify statistically significant connections (in the group of patients with ischemic cardiomyopathy: with the level of MR‑proADM ‑ r=0,67, p=0,006, with the level of NT‑proBNP ‑ r=0,78, p<0,001; in the group of patients with myocardial infarction and preserved left ventricular ejection fraction: with MR‑proADM level ‑ r=‑0,52, p=0,024, with NT‑proBNP level ‑ r =‑0,38, p=0,037).Conclusion.The findings suggest a pathogenetic association between the biomarkers under study and the parameters of left ventricular‑arterial coupling interaction.

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