Abstract: TH-PO087
Casual Association of Oxidative Stress With Cardiorenal Syndrome in Pulmonary Hypertension: An Experimental Investigation and Its Clinical Implications
Session Information
- AKI: Mechanisms - I
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Author
- Farahmand, Firoozeh, Saint Louis University, Saint Louis, Missouri, United States
Background
AKI due to pulmonary hypertension (PH) has been associated with an increase in mortality. Studies have shown 36% of the patients with AKI and PH died in the hospital compared with 5% in the PH group who did not develop AKI and retrospective study of hospitalized patients and PH registries shows AKI and CKD in 4%–50% of patients and renal insufficiency associates with poor prognosis. However, there is hardly any data available regarding pathogenesis of complex interplay of kidney, lung and the heart. To investigate experimental model of PH without left ventricular failure is essential to develop novel therapeutic targets.
Methods
In a chemically induced experimental model of PH with right ventricle( RV) dusfunction and AKI in rats we investigated whether antioxidant has cardiorenal protective effect & would this treatment modify oxidative stress in kidney & heart. Rats were divided into 3 groups ; control, CRS and CRS+ Antioxidant Prob( tretaed 1 wk pre & 1 wk post chemical injection). Rats were assesed with serial doppler echo for 3 wk to monitor PH via Pulmonary Artery Acceleration (PAAT), ejection fraction (EF) & RV hypertrophy (RVH). At 3 wk heart & kidney tissue and plasma were used to analyze antioxidant enzymes; superoxide dismutase (SOD) and glutathione peroxidase (GSHPx), as well as lipid peroxidation to assess oxidative stress. After sacrificing animals, hearts and kidneys were removed for histopathology. To assess congestion, pieces of tissue from the lung, kidney and the RV were removed to obtain the wet/dry weight ratio.
Results
in 3 wk, CRS group showed signs of progressive respiratory distress & doppler Echo demonstrated decrease in PAAT an indication of pulmonary hypertension, increase RVSP & normal EF. Oxidative stress in kidney and the RV was associated with decrease in antioxidant enzyme activities of SOD and GSHPx. Light and electron microspcopy of the Kidney showed ATN. Wet/dry weight showed mild congestion in the lung but not in the kidney and the heart. In CRS+ antioxidant PROB these changes were not observed.
Conclusion
Cardiorenal protective effect of antioxidant and abscence of renal congestion- a potential contributor in CRS- suggest a cause-effect relationship between oxidative stress and CRS in PH.Targetting oxidative stress may lead to novel therapeutic strategies to improve outcome.