Autologous Skeletal Myoblast Transplantation Improved Hemodynamics and Left Ventricular Function in Chronic Heart Failure Dogs
Document Type
Article
Publication Date
11-1-2005
Description
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/dtmax and LV volume determination. Each dog underwent baseline assessment in a conscious state. CHF (20% to 30% reduction in dP/dtmax 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 × 108 to 8.3 × 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/dtmax (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.
Citation Information
He, Kun Lun; Yi, Geng Hua; Sherman, Warren; Zhou, Hua; Zhang, Ge Ping; Gu, Anguo; Kao, Race; Haimes, Howard B.; Harvey, John; Roos, Eric; White, Desmond; Taylor, Doris A.; Wang, Jie; and Burkhoff, Daniel. 2005. Autologous Skeletal Myoblast Transplantation Improved Hemodynamics and Left Ventricular Function in Chronic Heart Failure Dogs. Journal of Heart and Lung Transplantation. Vol.24(11). 1940-1949. https://doi.org/10.1016/j.healun.2005.02.024 PMID: 16297802 ISSN: 1053-2498