Correlation of autologous skeletal myoblast survival with changes in left ventricular remodeling in dilated ischemic heart failure

Patrick I. McConnell, Carlos L. Del Rio, Douglas B. Jacoby, Martina Pavlicova, Pawel Kwiatkowski, Agatha Zawadzka, Jonathan H. Dinsmore, Louis Astra, Sheik Wisel, Robert E. Michler

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalJournal of Thoracic and Cardiovascular Surgery
Volume130
Issue number4
DOIs
StatePublished - Oct 2005
Externally publishedYes

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Skeletal Myoblasts
Ventricular Remodeling
Heart Failure
Cardiomyoplasty
Stroke Volume
Sheep
Transplantation
Skeletal Muscle
Myoblasts
Left Ventricular Function
Dilatation
Coronary Vessels
Hemodynamics
Blood Pressure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Correlation of autologous skeletal myoblast survival with changes in left ventricular remodeling in dilated ischemic heart failure. / McConnell, Patrick I.; Del Rio, Carlos L.; Jacoby, Douglas B.; Pavlicova, Martina; Kwiatkowski, Pawel; Zawadzka, Agatha; Dinsmore, Jonathan H.; Astra, Louis; Wisel, Sheik; Michler, Robert E.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 130, No. 4, 10.2005.

Research output: Contribution to journalArticle

McConnell, Patrick I. ; Del Rio, Carlos L. ; Jacoby, Douglas B. ; Pavlicova, Martina ; Kwiatkowski, Pawel ; Zawadzka, Agatha ; Dinsmore, Jonathan H. ; Astra, Louis ; Wisel, Sheik ; Michler, Robert E. / Correlation of autologous skeletal myoblast survival with changes in left ventricular remodeling in dilated ischemic heart failure. In: Journal of Thoracic and Cardiovascular Surgery. 2005 ; Vol. 130, No. 4.
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abstract = "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.",
author = "McConnell, {Patrick I.} and {Del Rio}, {Carlos L.} and Jacoby, {Douglas B.} and Martina Pavlicova and Pawel Kwiatkowski and Agatha Zawadzka and Dinsmore, {Jonathan H.} and Louis Astra and Sheik Wisel and Michler, {Robert E.}",
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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.

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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