Intramyocardial transplantation of autologous myoblasts: can tissue processing be optimized?
BACKGROUND
Autologous skeletal myoblast (SM) transplantation improves function of infarcted myocardium, but pretransplantation cultures remain a complex process. This study assessed whether it could be optimized by muscle preconditioning with the local anesthetic bupivacaine or even bypassed with the use of the so-called mince technique.


RESULTS
Muscle preconditioning consisted of intramuscular injections of the tibialis anterior of rats, 2 days before harvest. After 7 days of culture, the number of available myoblasts was significantly increased compared with nonconditioned controls (1 683 147 versus 85 300, P:=0.0013). The mince technique was then assessed. A myocardial infarction was created in 66 rats by coronary artery ligation. One week later, rats were reoperated on and intramyocardially injected with culture medium alone (controls, n=23), autologous cultured SM (3.5 x 10(6), n=21), or autologous muscle minced into a fine slurry, which was immediately transplanted (n=22). All muscles had been preconditioned. Left ventricular function was assessed by 2D echocardiography. Whereas end-diastolic volumes expanded over time in all groups, left ventricular ejection fraction (%, mean+/-SEM) was increased only in the cultured SM-transplanted group at 1 (P:=0. 0006) and 2 months (P:=0.0008) versus baseline (37.52+/-1.92 and 40. 92+/-2.17 versus 30.34+/-1.74), with a significant additional benefit between 1 and 2 months (P:=0.0069).


CONCLUSIONS
Cell culture remains mandatory for SM transplantation to be successful but, in a clinical perspective, this process can be made more expeditious by preharvest muscle conditioning with bupivacaine, which greatly enhances the baseline cell yield.
Pouzet
B
B
Service de Chirurgie Cardiovasculaire, Groupe Hospitalier Bichat-Claude Bernard, Paris, France.
Vilquin
J T
JT
Hagège
A A
AA
Scorsin
M
M
Messas
E
E
Fiszman
M
M
Schwartz
K
K
Menasché
P
P
D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004452:Echocardiography; D006085:Graft Survival / Q000187:drug effects; D007150:Immunohistochemistry; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014182:Transplantation, Autologous; D016277:Ventricular Function, Left / Q000502:physiology
D018995:Myosin Heavy Chains; D002045:Bupivacaine