Correlation of autologous skeletal myoblast survival with changes in left ventricular remodeling in dilated ischemic heart failure.
OBJECTIVE
The effect of autologous skeletal myoblast transplantation has not been rigorously studied in the setting of end-stage ischemic heart failure free of concomitant coronary revascularization. The aims of the present study were to determine autologous skeletal myoblast survival and its effects on left ventricular function and remodeling in sheep with dilated ischemic heart failure.


METHODS
Ischemic heart failure (left ventricular ejection fraction, 30% +/- 2%; left ventricular end-systolic volume index, 82 +/- 9 mL/m2) was created in sheep (n = 11) with serial left circumflex coronary artery microembolizations. Instruments were inserted for the long-term determination of left ventricular global and regional dimensions, hemodynamics, and pressure-volume analysis after autologous skeletal myoblast transplantation (approximately 3.0 x 10(8) myoblasts; heart failure plus autologous skeletal myoblast group, n = 5) or without (heart failure-control group, n = 6). Measurements were performed in conscious animals.


RESULTS
Autologous skeletal myoblast-derived skeletal muscle was found in all injected animals at 6 weeks. In ischemic heart failure, autologous skeletal myoblast cardiomyoplasty failed to improve systolic (left ventricular ejection fraction, 29% +/- 4%; dP/dT(max), 2863 +/- 152 mm Hg/s; end-systolic elastance, 1.6 +/- 0.22) or diastolic (left ventricular end-diastolic pressure, 21 +/- 2 mm Hg; time constant of relaxation (Tau), 34 +/- 4 ms; dP/dT(min), -1880 +/- 68 mm Hg/s) function. There was, however, attenuation in the left ventricular dilatation after autologous skeletal myoblast transplantation (change in end-systolic volume index, 14% +/- 4% vs 32% +/- 6%; P < .05). The effects of autologous skeletal myoblast-derived skeletal muscle were exclusive to the left ventricular short-axis dimension and dependent on autologous skeletal myoblast survival (R2 = 0.59, P = .006, n = 11).


CONCLUSIONS
Autologous skeletal cardiomyoplasty was able to attenuate left ventricular remodeling in sheep with end-stage ischemic heart failure.
McConnell
Patrick I
PI
Department of Surgery, The Ohio State University, Columbus, Ohio, USA.
del Rio
Carlos L
CL
Jacoby
Douglas B
DB
Pavlicova
Martina
M
Kwiatkowski
Pawel
P
Zawadzka
Agatha
A
Dinsmore
Jonathan H
JH
Astra
Louis
L
Wisel
Sheik
S
Michler
Robert E
RE
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000473:pathology / Q000601:surgery*; D002470:Cell Survival; D006333:Heart Failure / Q000473:pathology / Q000601:surgery*; D032448:Myoblasts, Skeletal / Q000637:transplantation*; D017202:Myocardial Ischemia / Q000473:pathology / Q000601:surgery*; D012756:Sheep; D020257:Ventricular Remodeling