Objectives: The objective of this study was to determine whether hypoxic preconditioning (HP) could lessen the myocardial increase in [Na+](i), thus protecting the aging myocardium against ischemia. Background: A decrease in ischemic tolerance with aging is associated with an accelerated increase in [Na+](i) during ischemia. Ischemic preconditioning fails to protect the middle-aged and senescent myocardium against ischemia. Methods: Isolated hearts of young adult (12-week-old), middle-aged (50-week-old) and senescent (100-week-old) Fischer 344 rats were subjected to 25 min of ischemia with or without HP followed by 30 min of reperfusion. Left ventricular (LV) function, myocardial energy metabolites and [Na+](i) were measured. Results: In the older groups, the recovery of LV function and high-energy phosphates (HEPs) was lower with an increased release of creatine kinase (CK) during reperfusion than in the young group. The increased [Na+](i) at the end of ischemia was greater in the former groups than in the young group. HP decreased myocardial glycogen and lessened the increased [Na+](i) in the young group, resulting in an improved recovery of LV function and HEPs, as well as decreased CK release. However, the levels of glycogen before HP in the older groups were higher than in the young group and its levels after HP were similar to that before HP in the young group. HP did not affect the [Na+](i), exacerbated CK release and inhibited the recovery of LV function and HEPs in the older groups. Conclusions: HP failed to lessen the increased [Na+](i) or to protect the aging hearts, probably due to the preexistence of increased glycogen level.
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