TY - JOUR
T1 - Correlation of autologous skeletal myoblast survival with changes in left ventricular remodeling in dilated ischemic heart failure
AU - McConnell, Patrick I.
AU - Del Rio, Carlos L.
AU - Jacoby, Douglas B.
AU - Pavlicova, Martina
AU - Kwiatkowski, Pawel
AU - Zawadzka, Agatha
AU - Dinsmore, Jonathan H.
AU - Astra, Louis
AU - Wisel, Sheik
AU - Michler, Robert E.
N1 - Funding Information:
D.B.J., J.H.D., and A.Z. are employees of GenVec, Inc. P.I.M. was supported in part by a Post Doctoral Fellowship from the Ohio Valley Affiliate, American Heart Association.
PY - 2005/10
Y1 - 2005/10
N2 - Objectives: 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 × 108 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/dTmax, 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/dTmin, -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.
AB - Objectives: 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 × 108 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/dTmax, 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/dTmin, -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.
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U2 - 10.1016/j.jtcvs.2005.02.030
DO - 10.1016/j.jtcvs.2005.02.030
M3 - Article
C2 - 16214511
AN - SCOPUS:26444587080
SN - 0022-5223
VL - 130
SP - 1001.e1-1001.e12
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
IS - 4
ER -