Angiogenic pretreatment to enhance myocardial function after cellular cardiomyoplasty with skeletal myoblasts.
OBJECTIVE
Improvements in ventricular function after cellular cardiomyoplasty appear to be limited by the poor survival of the cellular implants. Angiogenic pretreatment of infarcted myocardium may improve implanted cell survival and consequently myocardial function.


METHODS
Fischer 344 rats underwent coronary artery ligation and injection of an adenovirus encoding vascular endothelial growth factor 121 or of saline solution at increasing intervals after ligation. Myocardial perfusion and mass preservation were assessed. On the basis of these data, four groups of animals underwent coronary ligation and adenovirus with or without syngeneic skeletal myoblast administration: (1) adenovirus at ligation and myoblasts 3 weeks later (n = 7), (2) saline solution at ligation and myoblasts 3 weeks later (n = 8), (3) saline solution at ligation and 3 weeks later (n = 8), and (4) saline solution at ligation and adenovirus with myoblasts 3 weeks later (n = 5). Left ventricular ejection fraction was analyzed by echocardiography before coronary ligation and 3 and 5 weeks later, after which cell survival was assessed in harvested tissues.


RESULTS
Myocardial infarct perfusion was at least 50% greater in animals treated with adenoviral vector than with saline solution immediately after ligation (P < .02). In comparison, delayed adenovirus administration did not significantly diminish infarct perfusion but resulted in decreased myocardial preservation (P < .05). Accordingly, adenovirus administration nearly tripled implanted myoblast survival relative to saline solution-treated animals (P = .004). Left ventricular ejection fraction was improved, however, only after cell implantation with adenovirus pretreatment (P = .027).


CONCLUSIONS
Angiogenic strategies can help to preserve myocardium jeopardized by acute coronary occlusions. Angiogenic pretreatment enhances the efficacy of cellular cardiomyoplasty.
Retuerto
Mauricio A
MA
Evanston Northwestern Healthcare, Evanston, Ill, USA.
Beckmann
James T
JT
Carbray
JoAnn
J
Patejunas
Gerald
G
Sarateanu
Sorin
S
Kane
Bonnie J
BJ
Smulevitz
Beverly
B
McPherson
David D
DD
Rosengart
Todd K
TK
D000256:Adenoviridae; D000704:Analysis of Variance; D042501:Angiogenic Proteins / Q000494:pharmacology*; D000818:Animals; D001707:Biopsy, Needle; D018421:Cardiomyoplasty / Q000379:methods*; D002470:Cell Survival; D004195:Disease Models, Animal; D004452:Echocardiography; D008297:Male; D032448:Myoblasts, Skeletal / Q000637:transplantation*; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D010784:Photomicrography; D011336:Probability; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D015996:Survival Rate; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D018487:Ventricular Dysfunction, Left / Q000473:pathology* / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000502:physiology
D042501:Angiogenic Proteins; D042461:Vascular Endothelial Growth Factor A