Pathophysiology of Cardiorenal Syndrome in an Experimental Model Due to Isolated Right Ventricle Failure: Beyond Systemic Congestion

Background: Cardiorenal syndrome (CRS) and right heart failure (RHF) have complex and interrelated pathophysiology that involve mechanisms beyond isolated dysfunction of the heart and kidneys. This study investigates changes in antioxidants and oxidative stress in the right ventricle( RV) and the kidney as well as systemic congestion in CRS. This will shed light on pathophysiology based new therapeutic targets and preventive measures in CRS in addition to symptomatic relief with diuretics. Methods: CRS due to isolated RVF was produced in rats by a single injection of ALK. Animals were observed daily for any clinical signs of dyspnea, cyanosis , subcutaneous edema and ascites. At 1 week post injection serial echocardiography was performed to monitor cardiac function. RV systolic pressure (RVSP), RV hypertrophy (RVH), and RV function, RV and kidney levels of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSHPx) and lipid peroxidation (LPX) were measured. After sacrificing animals, hearts and kidneys were removed for histopathology. Lung and liver wet to dry weight ratio were measured to investigate pulmonary edema and liver congestion. Results: At 1 week post ALK injection renal histopathology was consistent with CRS. There was no clinical sign of fluid overload. Antioxidant enzymes activities including SOD and GSHPx were decreased in the kidney and the RV. There was LPX in the kidney and the RV. RV pressure overload and RV hypertrophy with no RV dysfunction were observed. There was no lung or liver congestion. Conclusion: New & noteworthy: This experimental model of CRS due to isolated RV dysfunction provides novel data that oxidative stress is the key contributor to pathophysiology of RV-Kidney deleterious cross talk and systemic congestion develops in later stage. Thus, antioxidants may have a crucial role in management of CRS.