Abstract
Development of Type 2 Diabetes (T2D) is associated with cardiac comorbidities linked to micro- and macro-vasculature defects. The aim of this work was to evaluate age-dependent changes in heart function by echocardiography in ZSF1 rats (Zucker fatty/Spontaneously hypertensive heart failure F1 hybrid), a model of metabolic syndrome. Male ZSF1 rats were studied at 12-18-24-45-57 weeks (W) of age in comparison to age-matched male lean ZSF1 rats. Left ventricular (LV) dimensions were measured by echocardiography in parasternal short axis view and M-mode to calculate Ejection Fraction (EF) and Fractional Shortening (FS). E and A waves were measured in parasternal four-chamber view (B-mode). Blood pressure (BP) was monitored by tail-cuff, cardiac structures by histology and sensitivity to ischemia by Langendorff method. At all ages, lean ZSF1 and ZSF1 rats displayed moderate hypertension. ZSF1 rats were heavier (+47.4% body weight (BW) at 45W); their left ventricular mass was similar to lean at 12W but increased by +46.4% at 45W. ZSF1 rats had lower EF and FS than lean rats from the age of 24W (respectively -5% and -10%), and E/A wave ratio was lowered by 24% at 45W. Moreover, their hearts were more sensitive to ischemia. Additionally ZSF1 rats exhibited deterioration mainly on kidney and heart structure along aging. With age, ZSF1 rats exhibit cardiac hypertrophy, deterioration of diastolic and systolic functions, and increased sensivity to ischemia. ZSF1 rats are a promising model for evaluating effects of drugs on cardiac function by echocardiography in the context of metabolic syndrome.
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