TY - JOUR
T1 - Angiogenic growth factors and/or cellular therapy for myocardial regeneration
T2 - A comparative study
AU - Chachques, Juan C.
AU - Duarte, Fabricio
AU - Cattadori, Barbara
AU - Shafy, Abdel
AU - Lila, Nermine
AU - Chatellier, Gilles
AU - Fabiani, Jean Noel
AU - Carpentier, Alain F.
PY - 2004/8
Y1 - 2004/8
N2 - 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.
AB - 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.
KW - 16,17,18,23
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U2 - 10.1016/j.jtcvs.2004.04.007
DO - 10.1016/j.jtcvs.2004.04.007
M3 - Article
C2 - 15282461
AN - SCOPUS:3242765432
VL - 128
SP - 245
EP - 253
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
SN - 0022-5223
IS - 2
ER -