The role of ventricular remodeling in the early decompensation of cardiorenal syndrome: Insight from studies with Ren-2 transgenic hypertensive rats subjected to volume overload induced using aorto-caval fistula

The aim of the present study was to evaluate the role of the left ventricle (LV) remodeling in the process of the transition from the compensation to the decompensation phase of cardiorenal syndrome. Ren-2 transgenic rats (TGR) with aorto-caval fistula (ACF) were used as the model of cardiorenal syndrome. Two weeks after ACF creation or sham operation, heart morphological parameters, cardiac structure and function were assessed by echocardiography and invasive pressure-volume analysis. This time point was chosen because two weeks after ACF the TGR still exhibit 100% survival rate and are in the transition phase from the compensation to the decompensation of cardiorenal syndrome. Our results at this stage show: (i) ACF TGR have already fully developed eccentric LV hypertrophy as compared with sham-operated TGR which exhibited signs of LV concentric hypertrophy; (ii) the increase in whole heart weight in ACF TGR was dominantly mediated by right ventricle (RV) hypertrophy, whereas the increase in the LV mass was minimal; (iii) ACF TGR displayed, besides bilateral ventricular dilatation, significant impairment of LV systolic functions whereas RV systolic functions were not impaired as compared with sham-operated TGR. Based on our present results, we propose that the inability of the LV to develop an appropriate hypertrophic response leads to maladaptive ventricular remodeling, which is likely a crucial factor in the process of the transition from the compensation to the decompensation phase of cardiorenal syndrome.