P098 CARDIAC REMODELING IN MICE TREATED WITH SODIUM OXALATE AND AORTIC STENOSIS

Background: Cardiovascular Diseases are one of the main global public health problems, with increasing mortality due to population aging and Hypertension (HTN). HTN is a risk factor for other diseases, such as aortic stenosis, renal dysfunction, and cardiac hypertrophy (CH). The hemodynamic overload caused by HTN affects the heart and kidneys, but the exact mechanisms of these alterations are not fully understood. Experimental models help study these mechanisms; however, a well-established model of CH with cardiorenal dysfunction does not yet exist. Objective: to evaluate whether the combination of cardiac hypertrophy, induced by transverse aortic constriction (TAC), and renal injury, induced by soluble sodium oxalate (OXA), can be a new model of CH with cardiorenal dysfunction. Methods: Male C57BL mice were randomized as follows: SHAM, receiving saline or OXA solution, and TAC, receiving saline or OXA solution. Echocardiography, direct blood pressure (BP) recording, metabolic cage, histology were performed to evaluate cardiac and renal function, hemodynamics, autonomic modulation, and baroreflex. Results: The TAC+OXA group showed the highest systolic BP(SBP) (SBP: SHAM: 122±5.24 vs. TAC+OXA: 160±5.24 mmHg, p<0.01), increased double product (DP) (DP: SHAM: 64.65±4.76 mmHg/bpm vs. TAC: 89.53±5.85 mmHg/bpm, p=0.02), significant reduction in autonomic modulation (RMSSD: OXA: 12.5±1.8 vs. TAC+OXA: 2.8±0.2 ms, p<0.01) and reflex tachycardia, eccentric hypertrophy, and worse renal function. The TAC group showed eccentric hypertrophy, increased BP variability (SD-SBP: SHAM: 2.97±0.07 mmHg vs. TAC: 5.63±0.57 mmHg, p≤0.01), diastolic dysfunction, and dilated left ventricle in diastole. The OXA group showed increased autonomic modulation and heart rate variability, renal damage characterized by inflammation, proximal tubule damage, and interstitial fibrosis when associated with TAC. All treated groups showed a significant reduction in reflex tachycardia. Conclusion: Transverse aortic constriction combined with OXA gavage is a model of CH with renal dysfunction, as the combination caused more significant renal damage, systemic hypertension, decreased autonomic modulation and baroreflex sensitivity, and eccentric hypertrophy with subsequent LV diastolic dysfunction.