scholarly journals Nonocclusive multivessel intracoronary infusion of allogeneic cardiosphere-derived cells early after reperfusion prevents remote zone myocyte loss and improves global left ventricular function in swine with myocardial infarction

2019 ◽  
Vol 317 (2) ◽  
pp. H345-H356 ◽  
Author(s):  
Gen Suzuki ◽  
Brian R. Weil ◽  
Rebeccah F. Young ◽  
James A. Fallavollita ◽  
John M. Canty
Keyword(s):  
Myocardial Infarction ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Viable Myocardium ◽  
Left Ventricular Ejection ◽  
Intracoronary Infusion ◽  
Remote Zone ◽  
Myocyte Apoptosis ◽  
Myocyte Proliferation ◽  
Stop Flow

Intracoronary cardiosphere-derived cells (icCDCs) infused into the infarct-related artery reduce scar volume but do not improve left ventricular (LV) ejection fraction (LVEF). We tested the hypothesis that this reflects the inability of regional delivery to prevent myocyte death or promote myocyte proliferation in viable myocardium remote from the infarct. Swine ( n = 23) pretreated with oral cyclosporine (200 mg/day) underwent a 1-h left anterior descending coronary artery (LAD) occlusion, which reduced LVEF from 61.6 ± 1.0 to 45.3 ± 1.5% 30 min after reperfusion. At that time, animals received global infusion of allogeneic icCDCs ( n = 8), regional infusion of icCDCs restricted to the LAD using the stop-flow technique ( n = 8), or vehicle ( n = 7). After 1 mo, global icCDCs increased LVEF from 44.8 ± 1.9 to 60.8 ± 3.8% ( P < 0.05) with no significant change after LAD stop-flow icCDCs (44.8 ± 3.6 to 50.9 ± 3.1%) or vehicle (46.5 ± 2.5 to 47.7 ± 2.6%). In contrast, global icCDCs did not alter infarct volume (%LV mass) assessed at 2 days (11.2 ± 2.3 vs. 12.6 ± 2.3%), whereas it was reduced after LAD stop-flow icCDCs (7.1 ± 1.1%, P < 0.05). Histopathological analysis of remote myocardium after global icCDCs demonstrated a significant increase in myocyte proliferation (147 ± 32 vs. 14 ± 10 nuclei/106 myocytes, P < 0.05) and a reduction in myocyte apoptosis (15 ± 9 vs. 46 ± 10 nuclei/106 myocytes, P < 0.05) that increased myocyte nuclear density (1,264 ± 39 vs. 1,157 ± 33 nuclei/mm2, P < 0.05) and decreased myocyte diameter (13.2 ± 0.2 vs. 14.5 ± 0.3 μm, P < 0.05) compared with vehicle-treated controls. In contrast, remote zone changes after regional LAD icCDCs were no different from vehicle. These data indicate that changes in global LVEF after icCDCs are dependent upon preventing myocyte loss and hypertrophy in myocardium remote from the infarct. These arise from stimulating myocyte proliferation and reducing myocyte apoptosis indicating the importance of directing cell therapy to viable remote regions. NEW & NOTEWORTHY Administration of allogeneic cardiosphere-derived cells to the entire heart via global intracoronary infusion shortly after myocardial infarction favorably influenced left ventricular ejection fraction by preventing myocyte death and promoting myocyte proliferation in remote, noninfarcted myocardium in swine. In contrast, regional intracoronary cell infusion did not significantly affect remote zone myocyte remodeling. Global cell administration targeting viable myocardium remote from the infarct may be an effective approach to prevent adverse ventricular remodeling after myocardial infarction.

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 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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