Diabetes related cardiomyopathy time dependent echocardiographic evaluation in an experimental rat model

Type I diabetes is associated with a unique form of cardiomyopathy in the absence of atherosclerosis. The mechanisms involved in this phenomenon are not defined, but in humans this is associated with initial diastolic dysfunction followed by altered contractile performance. A relevant animal model would provide opportunities for mechanistic studies and experimental therapeutics, but none have been previously established for this unique form of cardiac pathophysiology, particularly with respect to clinically relevant and time-dependent diastolic and systolic assessments. Here we tested the hypothesis that the streptozotocin rat model mimics human phenomena with respect to time-dependent diastolic and systolic performance deficits, and investigated a role for cardiac hypertrophy and/or fibrosis. Streptozotocin was dosed 65 mg/kg i.p. and cardiac performance was assessed longitudinally for 56 days using noninvasive echocardiographic techniques. Significant hyperglycemia was detected within 3 days and remained elevated throughout the study (p<0.05). Significant reductions in HR and diastolic performance (transmitral flow velocities and slopes) were observed within 3 days relative to age matched controls, and these reductions progressed throughout the 56 day study. In contrast, statistically significant systolic dysfunction (LV fractional shortening, cardiac output) and LV dilation were detected only after 35 days. Increases in LV size and/or extent of fibrosis were not observed at any time. These results demonstrate the value of echocardiographic methods for time-dependent diastolic and systolic assessments in rodent models. Furthermore, diastolic dysfunction precedes contractile abnormalities in the streptozotocin model, similar to events that occur in humans.