During early diastolic dysfunction, impaired LV relaxation and compliance is denoted by reduced magnitude of E wave, compensated by CPI-613 chemical information increased atrial contraction, resulting in reduced E:A ratio, as observed in diabetic Ren-2 animals . Also, impaired relaxation with prolonged deceleration time was observed in diabetic Ren-2 animals. However, interpretation of intrinsic diastolic properties using echocardiography is limited due to the preload dependence and recently highlighted heart rate dependence of the Doppler LV filling parameters. Consequently, load-insensitive measurements of chamber compliance were determined by examining end-diastolic pressure-volume relationship over varying loading conditions . We demonstrated that the marked reduction in chamber compliance in Ren-2 diabetic animals was attenuated by treatment with DiOHF antioxidant at the time point assessed. The rate of relaxation, measured by time constant of relaxation during the active phase of diastole, was also prolonged in Ren-2 diabetic animals. These data are consistent with the manifestation of LV diastolic dysfunction frequently found in diabetic patients without other known cardiac defects, such as atherosclerosis or hypertension . Martos et al. demonstrated that Nutlin-3 supplier markers of collagen turnover associated with active fibrotic processes were elevated in patients diagnosed with more severe phases of diastolic dysfunction. Using non-invasive monitoring of myocardial fibrosis in diabetic patients, the change in LV chamber compliance has been correlated to regulation of collagen turnover . In our study, the diabetic Ren-2 rats treated with DiOHF demonstrated significant reduction in cardiac myocyte hypertrophy and collagen types I and III. These structural effects may have contributed to the observed improvement in chamber compliance. In contrast, load-dependent indices of systolic function examined by fractional shortening and fractional area change showed no significant differences among diabetic and control Ren-2 animals. Similarly, the LV ejection fraction was within the normal range across all groups. The assessment of systolic function by conventional echocardiography is not only influenced by cardiac contractility but other factors including loading conditions and heart rate . In the present study, the ��gold standard�� invasive PV loops analysis of diabetic Ren-2 rats showed a reduction in the slope of preload recruitable stroke work relationship , indicative of subtle differences in cardiac contractility, that were not detected by echocardiography.