Early myocardial dysfunction in streptozotocin-induced diabetic mice: a study using in vivo magnetic resonance imaging (MRI).
BACKGROUND
Diabetes is associated with a cardiomyopathy that is independent of coronary artery disease or hypertension. In the present study we used in vivo magnetic resonance imaging (MRI) and echocardiographic techniques to examine and characterize early changes in myocardial function in a mouse model of type 1 diabetes.


METHODS
Diabetes was induced in 8-week old C57BL/6 mice with two intraperitoneal injections of streptozotocin. The blood glucose levels were maintained at 19-25 mmol/l using intermittent low dosages of long acting insulin glargine. MRI and echocardiography were performed at 4 weeks of diabetes (age of 12 weeks) in diabetic mice and age-matched controls.


RESULTS
After 4 weeks of hyperglycemia one marker of mitochondrial function, NADH oxidase activity, was decreased to 50% of control animals. MRI studies of diabetic mice at 4 weeks demonstrated significant deficits in myocardial morphology and functionality including: a decreased left ventricular (LV) wall thickness, an increased LV end-systolic diameter and volume, a diminished LV ejection fraction and cardiac output, a decreased LV circumferential shortening, and decreased LV peak ejection and filling rates. M-mode echocardiographic and Doppler flow studies of diabetic mice at 4 weeks showed a decreased wall thickening and increased E/A ratio, supporting both systolic and diastolic dysfunction.


CONCLUSIONS
Our study demonstrates that MRI interrogation can identify the onset of diabetic cardiomyopathy in mice with its impaired functional capacity and altered morphology. The MRI technique will lend itself to repetitive study of early changes in cardiac function in small animal models of diabetic cardiomyopathy.
Yu
Xichun
X
Department of Medicine, University of Oklahoma Health Sciences Center & VAMC, Oklahoma City, OK 73104, USA. xichun-yu@ouhsc.edu
Tesiram
Yasvir A
YA
Towner
Rheal A
RA
Abbott
Andrew
A
Patterson
Eugene
E
Huang
Shijun
S
Garrett
Marion W
MW
Chandrasekaran
Suresh
S
Matsuzaki
Satoshi
S
Szweda
Luke I
LI
Gordon
Brian E
BE
Kem
David C
DC
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D009202:Cardiomyopathies / Q000175:diagnosis / Q000209:etiology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000175:diagnosis / Q000503:physiopathology*; D005260:Female; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000201:enzymology; D009097:Multienzyme Complexes / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D013311:Streptozocin; D018487:Ventricular Dysfunction, Left / Q000209:etiology
D001786:Blood Glucose; D009097:Multienzyme Complexes; D013311:Streptozocin; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases