Exenatide Prevents Morphological and Structural Changes of Mitochondria Following Ischaemia-Reperfusion Injury.

BACKGROUND: Exenatide exerts cardioprotective effects by attenuating ischaemic reperfusion (IR) injury, possibly through activating the opening of mitochondrial ATP-sensitive potassium channels. We used atomic force microscopy (AFM) to investigate changes in mitochondrial morphology and properties in order to assess exenatide-mediated cardioprotection in IR injury. METHODS: We used an in vivo Sprague-Dawley rat IR model and ex vivo Langendorff injury model. In the left anterior descending artery (LAD) occlusion model, animals were randomly divided into three groups: sham-operated rats (Sham, n=5), IR-injured rats treated with placebo (IR, n=6), and IR-injured treated with exenatide (IR + EXE, n=6). For the Langendorff model, rats were randomly divided into two groups: IR injury with placebo (IR, n=4) and IR injury with exenatide (IR+EXE, n=4). Morphological and mechanical changes of mitochondria were analysed by AFM. RESULTS: Exenatide pre-treatment improved cardiac function as evidenced by improvement in echocardiographic results. The ratio of infarct area (IA) to risk area (RA) was significantly reduced in exenatide-treated rats. According to AFM, IR significantly increased the area of isolated mitochondria, indicative of mitochondrial swelling. Treatment with exenatide reduced the mitochondrial area and ameliorated the adhesion force of mitochondrial surfaces. CONCLUSIONS: Exenatide pre-treatment improves morphological and mechanical characteristics of mitochondria in response to IR injury in a rat model. These alterations in mitochondrial characteristics appear to play a cardioprotective role against IR injury.