Growth factors improve latissimus dorsi muscle vascularization and trophicity after cardiomyoplasty.
BACKGROUND
Dynamic cardiomyoplasty consists of wrapping the electrostimulated latissimus dorsi muscle (LDM) around the failed heart. Partial ischemia followed by atrophy of the middle and distal part of the LDM were observed in 30% of clinical cases after LDM flap elevation from its origin. In the current study, we hypothesized that local administration of growth factors at the LDM/epicardial interface could improve muscle vascularization and trophicity.


METHODS
In 24 sheep, dynamic cardiomyoplasty was performed using the left LDM. A multiperforated catheter was positioned at the LDM/epicardial interface for a weekly administration, during a 1-month period, of the following factors: basic fibroblast growth factor (bFGF, n = 6), vascular endothelial growth factor (VEGF, n = 6), and regenerating agent (RGTA, n = 6). Six sheep injected with phosphate-buffered saline (used for dilution of the growth factors) were used as a control group. At 3 months, angiographic, histologic, and histomorphometric studies were performed.


RESULTS
Angiographic studies of the animals treated with growth factors demonstrated hypervascularization due to the development of new vessels. Histomorphometric and histologic studies showed a significant increase in the number of capillaries and arterioles (100 fields/muscle) in the groups treated with bFGF (443.0 +/- 101.2, p < 0.01), RGTA (293.2 +/- 29.3, p < 0.05), and VEGF (246.5 +/- 45.9, p < 0.05), as compared with the control group (81.5 +/- 11.4). A significantly lower atrophy score was observed in the groups treated with bFGF (1.4 +/- 0.18, p < 0.05), RGTA (1.59 +/- 0.17, p < 0.05), and VEGF (1.96 +/- 0.14, NS), as compared with the control group (2.48 +/- 0.16).


CONCLUSIONS
Local administration at the heart/muscle interface of growth factors increases muscle vascularization and avoids muscle atrophy in an experimental cardiomyoplasty model, both of which are advantageous to the contracting LDM. The local growth factors delivery system used in this study appears efficient, easy to implant, and manipulate and safe.
Zakine
Gilbert
G
Department of Cardiovascular Surgery, Broussais Hospital, Paris, France.
Martinod
Emmanuel
E
Fornes
Paul
P
Sapoval
Marc
M
Barritault
Denis
D
Carpentier
Alain F
AF
Chachques
Juan Carlos
JC
D000818:Animals; D018421:Cardiomyoplasty; D003911:Dextrans / Q000008:administration & dosage / Q000494:pharmacology*; D016228:Endothelial Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D006133:Growth Substances / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D008222:Lymphokines / Q000008:administration & dosage / Q000494:pharmacology*; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D012756:Sheep; D019739:Skeletal Muscle Ventricle / Q000098:blood supply* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D003911:Dextrans; D016228:Endothelial Growth Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; C104129:RGTA11; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2