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Type: Artigo de periódico
Title: Effect of Cardiac Stem Cells on Left-Ventricular Remodeling in a Canine Model of Chronic Myocardial Infarction
Author: Welt, FGP
Gallegos, R
Connell, J
Kajstura, J
D'Amario, D
Kwong, RY
Coelho, O
Shah, R
Mitchell, R
Leri, A
Foley, L
Anversa, P
Pfeffer, MA
Abstract: Background-Regenerative medicine, including cell therapy, is a promising strategy for recovery of the damaged myocardium. C-kit-positive cardiac stem cells (CSCs) have been shown to improve myocardial function after ischemic injury in animal models and in early clinical experience. We used a chronic large animal model of myocardial infarction with substantial reductions in left-ventricular (LV) ejection fraction and adverse remodeling to examine the effect of late autologous CSC intramyocardial injection on long-term cardiac structure and function. Methods and Results-Thoracotomy and ligation of the proximal left anterior descending artery, additional diagonal branches, and atrial biopsy for CSC culture were performed in canines. Baseline cardiac MRI was performed at 6 weeks postinfarct followed by repeat thoracotomy for randomization to intramyocardial injection of CSCs (n=13) or vehicle alone (n=6). At 30 weeks postmyocardial infarction, repeat MRI was performed. Data were analyzed using nonparametric tests (Wilcoxon signed-rank and rank-sum tests). In control animals, LV end-systolic volume and end-diastolic volume increased from 6 to 30 weeks (median and interquartile range, 51.3 mL [43.3-57.4] to 76.1 mL [72.0-82.4]; P=0.03 and 78.5 mL [69.7-86.1] to 99.2 mL [97.1-100.4]; P=0.03). Left-ventricular ejection fraction declined further (35.2% [27.9-38.7] to 26.4% [22.0-31.0]; P=0.12). In the cell-treated animals, this late adverse LV remodeling was attenuated (LV end-systolic volume, 42.6 mL [38.5-50.5] to 56.1 mL [50.3-63.0]; P=0.01 versus control). There was a nonsignificant attenuation in the increase in LV end-diastolic volume (64.8 mL [60.7-71.3] to 83.5 mL [74.7-90.8]; P=0.14 versus control) and LV ejection fraction change over time differed (30.5% [28.4-33.4] to 32.9% [28.6-36.9]; P=0.04 versus control). Conclusions-Intramyocardial injection of autologous CSCs in a late phase model of chronic infarction resulted in less increase in LV end-systolic volume and preservation of LV ejection fraction.
Subject: animal model
chronic heart failure
remodeling heart failure
stem cells
Country: EUA
Editor: Lippincott Williams & Wilkins
Citation: Circulation-heart Failure. Lippincott Williams & Wilkins, v. 6, n. 1, n. 99, n. +, 2013.
Rights: fechado
Identifier DOI: 10.1161/CIRCHEARTFAILURE.112.972273
Date Issue: 2013
Appears in Collections:Unicamp - Artigos e Outros Documentos

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