Activation of AMPK alleviates cardiopulmonary bypass-induced cardiac injury via ameliorating acute cardiac glucose metabolic disorder.

Recent years, studies have demonstrated that hyperglycemia is one of the main manifestations after cardiac surgeries, which contributes to myocardial injuries and increases the chance of subsequent complications and mortality in such patients. However, strategies targeting at glucose metabolic disorder after cardiac surgeries to attenuate myocardial injuries are inadequately studied. In this study, a rat model of cardiopulmonary bypass (CPB) was applied to investigate the role of Adenosine 5'-monophosphate-activated protein kinase (AMPK) in modulating myocardial glucose metabolic-induced cardiac injuries after cardiac surgery. The results revealed that CPB elicited significant cardiac dysfunction, and pronouncedly elevated the markers of myocardial injuries including serum creatine kinase MB and cardiac troponin I. Additionally, blunted myocardial glucose uptake after CPB was associated with decreased membrane glucose transporter 4 (GLUT4) content. However, pretreatment of AMPK agonist 5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside (AICAR) at the beginning of CPB activated AMPK, enhanced phosphorylation of Akt substrate 160 (AS160), and increased myocardial membrane content of GLUT4. Meanwhile, improved myocardial glucose uptake and more importantly alleviated cardiac injury were also observed after CPB pretreated with AICAR. Moreover, the application of a mutant form of AS160 (AS160-4P) abolished the beneficial effect of AICAR, as evidenced by impaired cardiac glucose uptake, reduced myocardial membrane GLUT-4 translocation, increased cardiac injury markers, and deterioration of cardiac function after CPB. In conclusion, it was suggested in this study that preactivation of AMPK by AICAR improved myocardial glucose uptake by promoting AS160 dependent myocardial membrane GLUT-4 translocation, which ultimately provided a potent cardioprotective effect.
(© 2019 John Wiley & Sons Ltd.)