Abstract 17134: Cardiorenal Syndrome Arising From Chronic Diabetes Causes Maladaptive Carbohydrate Utilisation in the Heart and Kidneys

Clinical and epidemiological data have identified a cardiorenal syndrome (CRS), in which heart and/or kidney failure accelerates dysfunction in the other organ. There is a need for new therapeutics targeting the mechanisms that cause CRS, in order to treat the whole patient. Here, we tested the hypotheses that 1) chronic diabetes (aged Goto-Kakizaki [GK] rats) would yield a model of CRS, and 2) assessing in vivo cardiorenal metabolism using hyperpolarized 13C MR spectroscopy (MRS) would identify targets for CRS therapy. Statistical significance between GK rats and Wistar controls was considered at P<0.05. Glycated hemoglobin confirmed that GK rats were diabetic at 20 weeks. Forty-week-old GK rats (n=6) developed proteinuria, LV hypertrophy, and pulmonary congestion. Invasive pressure-volume loops (n=5) demonstrated preserved systolic, yet impaired diastolic, function. Histology demonstrated myocyte and glomerular hypertrophy, interstitial fibrosis and glomerulosclerosis. Intravenous infusion of hyperpolar...