Systolic contraction within aneurysmal rabbit myocardium following transplantation of autologous skeletal myoblasts.
OBJECTIVE
Transplantation of autologous skeletal myoblasts (SKMB) into infarcted heart (or cellular cardiomyoplasty, CCM) augments myocardial performance in animal models of myocardial infarction. However, the effect of CCM in the setting of ventricular aneurysm has not been evaluated. This study analyzes the effects of transplanted SKMB on regional wall motion in a rabbit model of postinfarct ventricular aneurysm. We hypothesize that CCM, performed early after myocardial infarction, prevents the progression of dyskinetic wall motion.


METHODS
Twenty-six rabbits underwent apical left ventricular cryoinfarction and soleus muscle biopsy for in vitro isolation of skeletal myoblasts. At 2 weeks postinfarct, the presence of ventricular aneurysm was detected in 23/26 animals by sonomicrometry and micromanometry. Seventeen of 23 animals were randomized to receive either 108 autologous myoblasts (CCM) or vehicle. Regional stroke work, percent systolic shortening, and synchronicity of regional wall motion were determined prior to, and four weeks following, injection (CCM; n = 9; vehicle, n = 8). Wall motion was evaluated under baseline and stress (dobutamine, 10 (g/kg/min) conditions. Six animals did not undergo randomization, but their hearts were used to measure the size of infarction.


RESULTS
Four weeks following treatment of animals with ventricular aneurysm, systolic contractile activity was present in most animals treated with myoblasts but in none treated with vehicle (5/7 versus 0/6, respectively, P < 0.05). Dobutamine tended to accentuate the differences seen at baseline between the groups.


CONCLUSIONS
This study demonstrates a high incidence of systolic contractile activity in a previously aneurysmal region of myocardium following CCM and may represent a novel therapy for the prevention and treatment of postinfarct aneurysm.
Emani
Sitaram M
SM
Department of Surgery, Duke University Medical Center, Durham, NC, USA.
Ellis
Matthew J
MJ
Dibernardo
Louis R
LR
Colgrove
Sharon
S
Glower
Donald D
DD
Taylor
Doris A
DA
D000818:Animals; D001794:Blood Pressure; D002316:Cardiotonic Agents / Q000494:pharmacology; D017690:Cell Transplantation / Q000379:methods*; D004280:Dobutamine / Q000494:pharmacology; D006322:Heart Aneurysm / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D006352:Heart Ventricles / Q000473:pathology; D018482:Muscle, Skeletal / Q000166:cytology; D032448:Myoblasts, Skeletal / Q000637:transplantation*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D011817:Rabbits; D013599:Systole / Q000187:drug effects; D014182:Transplantation, Autologous
D002316:Cardiotonic Agents; D004280:Dobutamine