Elevated Levels of Endogenous Adenosine Alter Metabolism and Enhance Reduction in Contractile Function During Low-flow Ischemia: Associated Changes in Expression of Ca2+-ATPase and Phospholamban

Adenosine has several potentially cardioprotective effects including vasodilatation, reduction in heart rate and alterations in metabolism. Adenosine inhibits catecholamine-induced increase in contractile function mainly through inhibition of phosphorylation of phospholamban (PLB), the main regulatory protein of Ca2+-ATPase in sarcoplasmic reticulum (SR), and during ischemia it reduces calcium (Ca2+) overload. In this study we examined the effects of endogenous adenosine on contractile function and metabolism during low-flow ischemia (LFI) and investigated whether endogenous adenosine can alter expression of the Ca2+-ATPase/PLB-system and other Ca2+-regulatory proteins. Isolated blood-perfused piglet hearts underwent 120 min 10% flow. Hearts were treated with either saline, the adenosine receptor blocker (8)-sulfophenyl theophylline (8SPT, 300 μ mol/l) or the nucleoside transport inhibitor draflazine (1 μ mol/l). During LFI, 8SPT did not substantially influence metabolic or functional responses. However, draflazine enhanced the reduction in heart rate, contractile force and MVO2, with less release of H+and CO2. Before LFI there were no significant differences between groups for any of the proteins (Ca2+-ATPase, ryanodine-receptor, Na+/K+-ATPase) or mRNAs (Ca2+-ATPase, PLB, calsequestrin, Na+/Ca2+-exchanger) measured. At end of LFI mRNA-level of PLB was higher in draflazine-treated hearts compared to both other groups (P