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J Thorac Cardiovasc Surg 2005;130:1001
© 2005 The American Association for Thoracic Surgery

Surgery for Acquired Cardiovascular Disease

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

Patrick I. McConnell, MD a , Carlos L. del Rio, BS b , Douglas B. Jacoby, PhD d , Martina Pavlicova, PhD c , Pawel Kwiatkowski, MD a , Agatha Zawadzka, MS d , Jonathan H. Dinsmore, PhD d , Louis Astra, MD a , Sheik Wisel, PhD a , Robert E. Michler, MD a , *

a Department of Surgery, The Ohio State University, Columbus, Ohio
b Department of Anesthesiology, The Ohio State University, Columbus, Ohio
c Department of Statistics, The Ohio State University, Columbus, Ohio
d GenVec Inc, Charlestown, Mass.

Read at the Thirtieth Annual Meeting of The Western Thoracic Surgical Association, Maui, Hawaii, June 23-26, 2004.

Received for publication August 10, 2004; revisions received January 25, 2005; accepted for publication February 10, 2005.

* Address for reprints: Robert E. Michler, MD, John and Jean McCoy Professor of Surgery, The Ohio State University Medical Center, Division of Cardiothoracic Surgery, 400 West 10th Ave, N847 Doan Hall, Columbus, OH 43210 (Email: michler.1{at}osu.edu).

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 x 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 (R 2 = 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.

17; 30; 34


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