Myocardial Stunning in the 5/6 Ablation/Infarction Model of Chronic Kidney Disease

Abstract

Myocardial stunning is a form of cardiac ischemia‐reperfusion (I/R) injury characterized by reversible contractile dysfunction following short bouts of ischemia without resulting necrosis. The purpose of this investigation was to assess myocardial stunning in the 5/6 Ablation/Infarction (AI) model of chronic kidney disease (CKD). Further, oxidative stress was explored as a potential mechanism for decreased nitric oxide (NO) and augmented I/R injury in CKD. Cardiac function was measured pre‐ and post 15min ischemia using an isolated working heart model, and left ventricular (LV) tissue was used for biochemical analysis. Cardiac function was impaired during post‐ischemia reperfusion (15–30min) in AI as indicated by cardiac output (66±4 vs. 41±4%PRE‐I p<0.05) and cardiac work (65±2 vs. 41±6%PRE‐I; p<0.05). Urinary NOx was lower in AI (1.3±0.2 vs. 0.6±0.1μM/24hr/100g; p<0.05) and accompanied by reduced LV eNOS (1.0±0.10 vs. 0.62±0.13; relative to β‐actin p<0.05) and NOx (18.9±2.2 vs. 11.3±2.3μM; p<0.05) Altered expression of LV antioxidant enzymes was also observed in AI (SOD1: 1.0±0.12 vs. 0.34±0.08; SOD2: 1.0±0.14 vs. 0.52±0.10; GPX: 1.0±0.1 vs. 1.3±0.08; relative to β‐actin all p<0.05). In conclusion, these findings suggest that myocardial stunning is augmented in CKD and could be, in part, the result of altered antioxidant defense leading to impaired NO‐mediated cardioprotection during I/R injury. Supported by: P20 RR016472