Preconditioning protects the severely atherosclerotic mouse heart

Background . Coronary atherosclerosis has profound effects on vascular and myocardial biology, and it has been speculated that the atherosclerotic heart does not benefit from ischemic preconditioning. Methods . To investigate if atherosclerosis would influence the preconditioning response, Apolipoprotein E/low density lipoprotein (LDL) receptor double knockout mice (ApoE/LDLr−/−) were fed an atherogenic diet (21% fat, 0.15% cholesterol) for 6 to 8 months. At that time, extensive atherosclerotic lesions throughout the coronary tree were seen in transverse sections stained with Oil Red-O. Hearts of ApoE/LDLr−/− mice were Langendorff-perfused with 40 minutes of global ischemia and 60 minutes reperfusion, and compared with C57BL/6 controls. Preconditioning with two episodes of 2 minutes of ischemia and 5 minutes reperfusion, or exposing the mice to a hyperoxic environment (O 2 > 98%) for 60 minutes before heart perfusion, was performed. Results . Hearts of mice with coronary atherosclerosis had worse postischemic function, and increased infarct size and troponin T release compared to hearts of C57BL/6 mice. Ischemic preconditioning improved postischemic ventricular function, and reduced myocardial infarct size and troponin T release in both normal and ApoE/LDLr−/− mice. The effects were most pronounced in ApoE/LDLr−/− hearts. Exposure to hyperoxia exerted a similar protection of function and cell viability of ApoE/LDLr−/− mice hearts. Conclusions . These findings suggest that the severely atherosclerotic heart may be protected by preconditioning induced by ischemia or hyperoxia.