Individual and combined effects of wheel running and ischemic preconditioning in protecting the rat heart from reperfusion injury.

It is well known that exercise training (TRN) and ischemic preconditioning (IPC) reduce cardiomyocyte (CM) death following ischemia and reperfusion (IR), but it is unknown if protection can be elicited by moderate exercise TRN or if the effects of TRN and IPC summate to generate greater protection than either protocol alone. To address these questions, we used wheel running, a moderate-intensity paradigm, to TRN male and female rats, and two IPC protocols. Hearts were studied ex vivo with regional ischemia (RI) produced by occluding the left anterior descending coronary artery for 30 min followed by 3 h reperfusion. IPC consisted of a 5-min period of global ischemia and either 5 (PC5) or 10 (PC10) min reperfusion before the initiation of index RI. We found that wheel running and PC10, but not PC5, reduced CM death compared with sedentary, with the TRN effect greater in males. TRN, but not IPC, showed functional protection by reducing the loss of left ventricular developed pressure. Surprisingly, the TRN and PC10 protection from cell death was not additive, suggesting that these modalities converge on the same pathway. We also showed that TRN significantly improved mitochondrial respiration and ΔΨm repolarization during oxidative phosphorylation after IR when compared with SED rats; the improved bioenergetics was associated with the increased prosurvival kinase, hexokinase II (HKII), translocation to mitochondria, which was mediated by increased total Akt and the phosphorylated Akt. We conclude that TRN-induced cardioprotection is mediated, in part, by preservation of mitochondrial bioenergetics likely mediated via the Akt-pAkt-HKII signaling pathway.NEW & NOTEWORTHY Our study produced the novel findings that wheel running in rats, a form of moderate-intensity continuous training (MICT), can provide protection against IR injury as evidenced by a reduction in cardiomyocyte death following 3 h reperfusion and that the protection generated by MICT and IPC is not additive. Importantly, we demonstrate for the first time that MICT-induced cardioprotection is associated with preservations of mitochondrial bioenergetics likely by the Akt-pAkt-HKII signaling pathway.