Autologous skeletal myoblast transplantation improved hemodynamics and left ventricular function in chronic heart failure dogs.
BACKGROUND
Previous studies have suggested that autologous skeletal myoblast transplantation (ASMT) improves left ventricular (LV) function in small animals after myocardial infarction. We tested the effects of ASMT on hemodynamics, LV function and remodeling in coronary microembolization-induced chronic heart failure (CHF) in conscious dogs.


METHODS
Nineteen dogs were continuously instrumented with LV pressure sensors and mid-myocardial sonomicrometry crystals for dP/dt(max) and LV volume determination. Each dog underwent baseline assessment in a conscious state. CHF (20% to 30% reduction in dP/dt(max) and LV end-diastolic pressure >16 mm Hg) was created by daily coronary microembolizations via a continuously implanted coronary catheter. Skeletal muscle biopsy was performed and myoblasts were isolated and expanded. Then 2.7 x 10(8) to 8.3 x 10(8) myoblasts were injected into the infarcted region of 11 dogs after establishment of CHF. Saline injection (sham) was performed in 8 control dogs. Animals were evaluated every 2 weeks for up to 10 weeks. Global ejection fraction was determined by echocardiography. The end-systolic pressure-end-systolic volume relationship (ESPVR) was analyzed by the Sonomicrometic system.


RESULTS
Compared with saline injection, ASMT significantly increased dP/dt(max) (105 +/- 9% vs 97 +/- 7%, values were expressed as percentage change from baseline CHF, p = 0.013) and ejection fraction (46 +/- 3% vs 40 +/- 2%, p = 0.034) at 10 weeks after myoblast transplantation. There was a significant leftward and upward shift of the ESPVR back toward normal at 10 weeks after myoblast transplantation (p = 0.034). Three animals labeled with BrdU myoblasts showed no histologic evidence of viable engraftment.


CONCLUSIONS
ASMT provided mild improvements in hemodynamics and LV function and reduced LV remodeling in conscious dogs with CHF.
He
Kun-Lun
KL
Department of Cardio-Nephrology, Chinese PLA General Hospital, Beijing, China. hekunlun2002@yahoo.com
Yi
Geng-Hua
GH
Sherman
Warren
W
Zhou
Hua
H
Zhang
Ge-Ping
GP
Gu
Anguo
A
Kao
Race
R
Haimes
Howard B
HB
Harvey
John
J
Roos
Eric
E
White
Desmond
D
Taylor
Doris A
DA
Wang
Jie
J
Burkhoff
Daniel
D
D000818:Animals; D002454:Cell Differentiation; D004195:Disease Models, Animal; D004285:Dogs; D006333:Heart Failure / Q000503:physiopathology*; D006439:Hemodynamics; D007150:Immunohistochemistry; D032448:Myoblasts, Skeletal / Q000637:transplantation*; D011184:Postoperative Period; D014182:Transplantation, Autologous; D016277:Ventricular Function, Left; D017725:Ventricular Pressure