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CLINICAL RESEARCH: HEART TRANSPLANTATION

Molecular normalization of dystrophin in the failing left and right ventricle of patients treated with either pulsatile or continuous flow-type ventricular assist devices

Matteo Vatta, PhD^*, Sonny J. Stetson, BSc^||¶, Shinawe Jimenez, MD^*, Mark L. Entman, MD^¶#, George P. Noon, MD^¶#, Neil E. Bowles, PhD^*, Jeffrey A. Towbin, MD^* and Guillermo Torre-Amione, MD, PhD^||¶,*

^* Department of Pediatrics (Cardiology), Baylor College of Medicine, Houston, Texas, USA
Department of Reproductive and Developmental Sciences, University of Trieste, Trieste, Italy
Section of Cardiology, Houston, Texas, USA
Cardiovascular Science, Houston, Texas, USA
^|| Molecular and Human Genetics), Houston, Texas, USA
^¶ The Winters Center for Heart Failure Research, Houston, Texas, USA
^# The Gene and Judy Campbell Laboratory for Cardiac Transplant Research, and the Methodist DeBakey Heart Center, Baylor College of Medicine, Houston, Texas, USA

Manuscript received April 16, 2003; revised manuscript received August 1, 2003, accepted September 22, 2003.

^* Reprint requests and correspondence: Dr. Guillermo Torre-Amione, Methodist DeBakey Heart Center and Baylor College of Medicine, 6550 Fannin, Ste. 1901, Houston, Texas 77030, USA.
gtorre{at}bcm.tmc.edu

OBJECTIVES: We investigated the integrity of dystrophin in left ventricle (LV) and right ventricle (RV) of patients with end-stage heart failure due to ischemic cardiomyopathy (IHD) or dilated cardiomyopathy (DCM), and compared the efficacy of pulsatile or continuous flow assist devices on dystrophin reverse remodeling.

BACKGROUND: Recently we demonstrated that the amino (N)-terminus of dystrophin is preferentially disrupted in failing LV myocardium irrespective the underlying etiology, and that this defect is reversed by mechanical unloading using left ventricular assist device (LVAD) therapy.

METHODS: Myocardial samples were obtained from seven normal controls, seven failing hearts (either DCM or IHD), and 14 failing-heart patients who underwent placement of either pulsatile (7 patients) or continuous flow (7 patients) LVADs for progressive refractory HF. The expression and integrity of dystrophin in these samples were determined by immunohistochemistry using antibodies against the N-terminal and carboxyl (C)-terminal domains.

RESULTS: Immunohistochemical staining identified disruption of the N-terminal dystrophin in both LVs and RVs of all seven failing-heart patients, whereas the C-terminus was normal. Furthermore, this disruption was reversed in 12 of the 14 patients after LVAD therapy using either pulsatile or continuous devices; the degree of the reverse remodeling was similar in both ventricles, although greater recovery was noted in patients treated with pulsatile flow devices.

CONCLUSIONS: Integrity of the N-terminus of dystrophin is a useful indicator of both LV and RV function. In addition to improving LV hemodynamics, LVAD therapy results in amelioration of the myocardial structure of the right cardiac chamber.

Abbreviations and Acronyms   BMD = Becker muscular dystrophy   DAPC = dystrophin-associated protein complex   DMD = Duchenné muscular dystrophy   HF = heart failure   IHD = ischemic cardiomyopathy   LV = left ventricle/ventricular   LVAD = left ventricular assist device   N = amino   RV = right ventricle/ventricular   XLCM = X-linked form of dilated cardiomyopathy

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