Influence of metformin and insulin on myocardial substrate oxidation under conditions encountered during cardiac surgery

Background: The influence of diabetic therapies on myocardial substrate selection during cardiac surgery is unknown but may be important to ensure optimal surgical outcomes. We hypothesized that metformin and insulin alter myocardial substrate selection during cardiac surgery and may affect reperfusion cardiac function. Methods: Rat hearts (n = 8 per group) were evaluated under 3 metabolic conditions: normokalemia, cardioplegia, or bypass. Groups were perfused with Krebs-Henseleit buffer in the presence of no additives, metformin, insulin, or both insulin and metformin. Perfusion buffer containing physiologic concentrations of energetic substrates with different carbon-13 (¹³C) labeling patterns were used to determine substrate oxidation preferences using ¹³C magnetic resonance spectroscopy and glutamate isotopomer analysis. Rate pressure product and oxygen consumption were measured. Results: Myocardial function was not different between groups. For normokalemia, ketone oxidation was reduced in the presence of insulin and the combination of metformin and insulin reduced fatty acid oxidation. Metformin reduced fatty acid and ketone oxidation during cardioplegia. Fatty acid oxidation was increased in the bypass group compared with all other conditions. Conclusion: Metformin and insulin affect substrate utilization and reduce fatty acid oxidation before reperfusion. These alterations in substrate oxidation did not affect myocardial function in otherwise normal hearts.