Early Detection of Myocardial Bioenergetic Deficits: A 9.4 Tesla Complete Non Invasive 31P MR Spectroscopy Study in Mice with Muscular Dystrophy.
BACKGROUND
Duchenne muscular dystrophy (DMD) is the most common fatal form of muscular dystrophy characterized by striated muscle wasting and dysfunction. Patients with DMD have a very high incidence of heart failure, which is increasingly the cause of death in DMD patients. We hypothesize that in the in vivo system, the dystrophic cardiac muscle displays bioenergetic deficits prior to any functional or structural deficits. To address this we developed a complete non invasive 31P magnetic resonance spectroscopy (31P MRS) approach to measure myocardial bioenergetics in the heart in vivo.


RESULTS
Six control and nine mdx mice at 5 months of age were used for the study. A standard 3D -Image Selected In vivo Spectroscopy (3D-ISIS) sequence was used to provide complete gradient controlled three-dimensional localization for heart 31P MRS. These studies demonstrated dystrophic hearts have a significant reduction in PCr/ATP ratio compare to normal (1.59±0.13 vs 2.37±0.25, p<0.05).


CONCLUSIONS
Our present study provides the direct evidence of significant cardiac bioenergetic deficits in the in vivo dystrophic mouse. These data suggest that energetic defects precede the development of significant hemodynamic or structural changes. The methods provide a clinically relevant approach to use myocardial energetics as an early marker of disease in the dystrophic heart. The new method in detecting the in vivo bioenergetics abnormality as an early non-invasive marker of emerging dystrophic cardiomyopathy is critical in management of patients with DMD, and optimized therapies aimed at slowing or reversing the cardiomyopathy.
Department of Medicine/Cardiology, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America.
Weina
W
Cui
Department of Medicine/Cardiology, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America.
Albert
A
Jang
Department of Medicine/Cardiology, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America.
Pengyuan
P
Zhang
Department of Integrative Biology & Physiology, University of Minnesota, Minneapolis, Minnesota, United States of America.
Brian
B
Thompson
Department of Integrative Biology & Physiology, University of Minnesota, Minneapolis, Minnesota, United States of America.
DeWayne
D
Townsend
Department of Integrative Biology & Physiology, University of Minnesota, Minneapolis, Minnesota, United States of America.
Joseph M
JM
Metzger
Department of Medicine/Cardiology, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America.
Jianyi
J
Zhang
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D020388:Muscular Dystrophy, Duchenne / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology
D000255:Adenosine Triphosphate