Background: Atherosclerosis in the coronary arteries is a gradual, progressive and chronic process that may result in significant occlusion and subsequent myocardial infarction. However, prior to occlusive coronary disease, parts of the myocardium will experience reduced blood flow. This low-flow ischaemia is likely to trigger significant metabolic remodelling. Aim: To determine the changes in myocardial energetics in a murine model of chronic coronary heart disease (CHD). Methods: 18 male apolipoprotein E knockout mice (ApoE-/-) were fed either a western-type high-fat diet (n=12; 21% lard and 0.15% cholesterol) or chow diet (n=6) for 24 weeks from weaning. High-fat diet ApoE-/- mice develop progressive atherosclerosis including in their coronary arteries (CHD). In contrast, littermates fed a chow diet exhibit no coronary disease (control). Ex-vivo hearts were perfused on a Langendorff apparatus with oxygenated Krebs solution. After 20 minutes of stabilization (pre-ischemia) hearts were snap frozen. The concentration of adenine nucleotides (ATP, ADP, AMP), inosine, hypoxanthine was determined using high pressure liquid chromatography (HPLC). Myocardial lactate was measured using a commercially available kit. Data are presented as Mean±SEM and significance assessed using an unpaired Student’s t-test. Results: There were no significant differences between ATP and ADP levels between groups. AMP nucleotide increased in coronary heart disease tissue compared with non-diseased control mice (CHD, 1.07 ± 0.11; control, 0.62 ± 0.045; p=0.013). Subsequently, the phosphorylation potential as measured by ATP/AMP ratio was significantly lower in the disease group (1.7 ± 0.2 vs. 2.6 ± 0.38; p<0.05). Additionally, the adenylate energy charge (AEC) was significantly lower in the diseased group (0.57 ± 0.02 vs. 0.65 ± 0.02, p=0.019). There were no differences in the tissue levels of lactate, inosine and hypoxanthine. Conclusion: The data obtained in this work suggests that hearts with progressive, chronic coronary disease are metabolically stressed compared to their control. This “ischaemic” stress is likely to trigger cellular remodelling including survival signalling which will impact upon their ability to respond to ischaemia and reperfusion injury.