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 a bsence of atherosclerosis. The mechanisms involved in this phenomenon are n ot defined, but in humans this is associated with initial. diastolic dysfun ction followed by altered contractile performance. A relevant animal model would provide opportunities for mechanistic studies and experimental therap eutics, but none have been previously established for this unique form of c ardiac pathophysiology, particularly with respect to clinically relevant an d time-dependent diastolic and systolic assessments. Here we tested the hyp othesis that the streptozotocin rat model mimics human phenomena with respe ct to time-dependent diastolic and systolic performance deficits, and inves tigated a role for cardiac hypertrophy and/or fibrosis. Streptozotocin was dosed 65mg/kg i.p. and cardiac performance was assessed longitudinally for 56 days using noninvasive echocardiographic techniques. Significant hypergl ycemia was detected within 3 days and remained elevated throughout the stud y (p<0.05). Significant reductions in HR and diastolic performance (transmi tral flow velocities and slopes) were observed within 3 days relative to ag e matched controls, and these reductions progressed throughout the 56 day s tudy. In contrast, statistically significant systolic dysfunction (LV fract ional shortening, cardiac output) and LV dilation were detected only after 35 days. Increases in LV size and/or extent of fibrosis were not observed a t any time. These results demonstrate the value of echocardiographic method s for time-dependent diastolic and systolic assessments in rodent models. F urthermore, diastolic dysfunction precedes contractile abnormalities in the streptozotocin model, similar to events that occur in humans. (C) 2001 Els evier Sciences Inc. All rights reserved.