Cardiac Dysfunction in the 5/6 Ablation‐Infarction Model of Chronic Kidney Disease

Abstract

The purpose of this investigation was to study cardiac function in a rodent model of chronic kidney disease (CKD). Cardiac function was measured in 5/6 ablation‐infarction (5/6 AI) and sham male Sprague Dawley rats 8‐weeks post‐surgery using an isolated working heart preparation. In addition, heart mass was determined and left ventricular (LV) tissue was used for biochemical analysis. Cardiac output was impaired in 5/6 AI at left atrial filling pressures of 13.5cmH2O (50±3 vs. 28±5ml/min; mean ± SEM), 17.5cmH2O (53±6 vs. 29±5ml/min), & 21.5cmH2O (53±6 vs. 30±5ml/min; all p<0.05), but not 9.5cmH2O (39±3 vs. 24±5ml/min; p>;0.05), while aortic pressure was maintained at 80cmH2O. Cardiac output was also impaired at aortic pressures of 60cmH2O (43±3 vs. 24±4ml/min) & 70cmH2O (45±3 vs. 24±4ml/min) with filling pressure set at 13.5cmH2O (all p<0.05). Heart mass was increased in 5/6 AI (3.5±0.3 vs. 4.9±0.4mg/g) and accompanied by increased LV NOX‐4 (1.0±0.1 vs. 1.5±0.1 relative to β‐actin p<0.05) and H2O2 (179±15 vs. 230±17nm/mg). The LV Nox‐2 subunit gp91phoxwas not increased in 5/6 AI (1.0±0.1 vs. 1.1±0.1 relative to β‐actin p>;0.05). In conclusion, cardiac hypertrophy & dysfunction are evident in CKD. These findings could be, in part, mediated by increased Nox‐4 and reactive oxygen species (ROS) production. However, further investigation is needed to clarify the role of NOX‐4 and ROS in uremic cardiomyopathy.