4-9) As a consequence of above pathologic mechanism, functionally, diastolic and systolic functions of ventricle are impaired,10),11) and subsequent structural changes are responsible for increased myocardial fibrosis and stiffness.1),12) After far-advanced structural changes, the impairment of damaged myocardial function may be irreversible. Therefore, detection
Inhibitors,research,lifescience,medical and treatment at early stage of DMCMP is considered to be important. However, there have been no effective available drugs for the treatment and prevention of ventricular dysfunction in DMCMP. To develop effective medication and to test for the efficacy of the drug, early detection of myocardial dysfunction using experimental animal model is very important. Although pressure-volume loop achieved by Inhibitors,research,lifescience,medical invasive hemodynamic measurement is known as the ‘gold standard’, it is very hard to operate and it has disadvantage of sacrificing the experimental animal after the operation,
and thus, recent attempts on early detection of myocardial dysfunction using echocardiography are being made. Therefore, we tested the usefulness of tissue Doppler imaging in terms Inhibitors,research,lifescience,medical of early detection of ventricular dysfunction in a rat model of DMCMP. Materials and Methods Animal model Eight weeks-aged male Sprague-Dawley (SD) rats were maintained on a 12 h light–dark cycle, with free access to standard chow. Diabetes mellitus was induced by a single intravenous injection of 70 mg/kg streptozocin (STZ) in a 0.1 M citrate buffer solution (Sigma, Munich, Germany), as previously described.13) Forty eight hours after treatment with STZ, tail vein blood glucose samples were measured with One Touch Horizon glucometer (U0126 Johnson & Johnson, California, Inhibitors,research,lifescience,medical USA) to confirm induction of diabetes (hyperglycemia >350 mg/dL). All rat which did not met diabetes criteria (blood
glucose >350 mg/dL) excluded from the study, and thus, 15 diabetes rats (DM, n=15) were fed for 10 weeks. Additionally, Inhibitors,research,lifescience,medical sex-age matched SD rat were treated with sodium citrate buffer only, all and referred to as the control group (control, n=10). All of the rats were housed in the Laboratory Animal Facility of the Clinical Research Institute of Seoul National University and the study protocol was approved by Institutional Animal Care and Use Committee of Seoul National University. Echocardiography Echocardiography was performed at baseline (before STZ injection), 10 weeks after diabetes induction. The rats were lightly sedated with intraperitoneal zolazepam (25 mg/kg) and xylazine (50 mg/kg). Images were acquired with a 12 MHz transducer connected to a Vivid-i echocardiography machine (GE Medical, Milwaukee, USA). M-mode and 2-dimensional echocardiography images at the papillary muscle level were acquired with a frame rate of 250-300/sec.