Glucose versus acetate as substrate during subtotal ischaemia

[摘要] ENGLISH ABSTRACT: Background: The provision of glucose (Glu) is beneficial during ischaemia (Opie,1970). Part of Glu protection may be due to Glu oxidation, specifically the Krebs Cycleand oxidative phosphorylation (Lopaschuk, 1998). Therefore, 30 mM acetate (Ac) mayhypothetically provide protection similar to 10 mM Glu providing that there is residualoxygen available to allow functioning of the Krebs Cycle and oxidative phosphorylation.Aim: The aim of this study was to establish an optimal Ac concentration at which theconsequences of ischaemia were minimal, to determine whether the protective effects ofGlu and. Ac is oxygen dependent, and to investigate whether equi-carbon concentrationsof Ac and Giu would offer similar protection during low flow ischaemia. Materials andMethods: Isolated rat hearts (n = 6-8) were perfused (Langendorff, 95% 02, 5% CO2)with 5 mM Ac for 30 minutes, followed by 2 ml/min low flow ischaemia with 1 mM or 5mM or 10 mM or 30 mM Ac or 10 mM Glu. Additional hearts were subjected to anoxiaduring the same period. All hearts were reperfused for 30 minutes under the preischaemicconditions. We measured the time to the onset of ischaemic contracture(TOIC), the percentage recovery of left ventricular developed pressure (L VDP), andtissue ATP, creatine phosphate, lactate, glycogen and cAMP content. Results: 5 mMand 10 mM Ac perfused hearts yielded optimal yet similar protection against theconsequences of ischaemia. In addition, Ac (5 mM) and Glu (10 mM) treated heartsperformed equally poorly in the absence of oxygen. This implies that the beneficialeffects conferred by Glu is oxygen dependent, due possibly to the activity of the KrebsCycle and oxidative phosphorylation. An equi-carbon concentration of Ac (30 mM)could not offer protection analogous to 10 mM Glu during oxygenated, low flowischaemic conditions. Instead, 10 mM Glu provided optimal protection against ischaemia while 30 mM Ac was associated with accelerated TOIC, reduced ATP andglycogen levels, elevated lactate and· cAMP levels, and weakened function uponreperfusion. Conclusion: Glu provided maximal protection against the consequences oflow flow ischaemia. However, this protection was dependent on the availability ofoxygen, suggesting that oxidative phosphorylation and Krebs Cycle activity maycontribute more to the protective effects of a particular substrate than previouslyanticipated.

[发布机构] Stellenbosch University