Angiogenic growth factors and/or cellular therapy for myocardial regeneration: A comparative study

Juan C. Chachques, Fabricio Duarte, Barbara Cattadori, Abdel Shafy, Nermine Lila, Gilles Chatellier, Jean Noel Fabiani, Alain F. Carpentier

Research output: Contribution to journalArticle

Abstract

Background Locally delivered angiogenic growth factors and cell implantation have been proposed for patients with myocardial infarcts without a possibility of percutaneous or surgical revascularization. The goal of this study was to compare the effects of these techniques in an experimental model of myocardial infarct. Methods Left ventricular myocardial infarction was created in 27 sheep by ligation of 2 coronary arteries. Three weeks after creation of the infarct, animals were randomized into 4 groups. In group 1, sheep received a culture medium injection to the infarct area (control group); group 2 underwent autologous myoblast implantation; group 3 received vascular endothelial growth factor; and group 4 received injection of both vascular endothelial growth factor and myoblasts. Evaluation included serum troponin IC levels, echocardiography (2-dimensional and color kinesis), and immunohistologic studies for quantitative analysis of capillaries (3 months after surgery). Results Four animals died of refractory ventricular fibrillation during myocardial infarction; 2 died after surgery because of stroke and 2 because of infections. Serum troponin increased to 45.6 ± 4.7 ng/mL at postinfarction day 2. Echocardiography at 3 months showed a significant limitation of left ventricular dilation in the cell group (57 ± 11.1 mL) and in the cell plus vascular endothelial growth factor group (58.6 ± 6.6 mL: control group, 74.4 ± 11.2 mL; vascular endothelial growth factor group, 68.1 ± 3.4 mL). Color kinesis echography showed important improvements of regional fractional area change in the cell group (from 13.6% ± 0.8% to 21.1% ± 1.5%) and in the cell plus vascular endothelial growth factor group (from 12.8% ± 0.9% to 18.7% ± 2.3%). The number of capillaries increased in the peri-infarct region of the vascular endothelial growth factor group (1036 ± 75: control group, 785 ± 31; cell group, 830 ± 75; cell plus vascular endothelial growth factor group, 831 ± 83). Conclusions In the cell therapy groups, regional ventricular contractility improved and heart dilatation was limited compared with either vascular endothelial growth factor or control; thus, postischemic remodeling was reduced. Angiogenesis was demonstrated in the vascular endothelial growth factor group, without improvement of ventricular function and remodeling. To improve local conditions for cell survival, further studies are warranted on prevascularization of myocardial scars with angiogenic therapy.

Original languageEnglish
Pages (from-to)245-253
Number of pages9
JournalJournal of Thoracic and Cardiovascular Surgery
Volume128
Issue number2
DOIs
Publication statusPublished - Aug 2004

Keywords

  • 16,17,18,23

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Fingerprint Dive into the research topics of 'Angiogenic growth factors and/or cellular therapy for myocardial regeneration: A comparative study'. Together they form a unique fingerprint.

  • Cite this

    Chachques, J. C., Duarte, F., Cattadori, B., Shafy, A., Lila, N., Chatellier, G., Fabiani, J. N., & Carpentier, A. F. (2004). Angiogenic growth factors and/or cellular therapy for myocardial regeneration: A comparative study. Journal of Thoracic and Cardiovascular Surgery, 128(2), 245-253. https://doi.org/10.1016/j.jtcvs.2004.04.007