Department of Physiological Sciences

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Browsing Department of Physiological Sciences by Subject "Acetates"

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    Glucose versus acetate as substrate during subtotal ischaemia
    (Stellenbosch : Stellenbosch University, 1999-12) Segadavan, Arisha; Van Rooyen, J.; Podzuweit, T.; Stellenbosch University. Faculty of Sciences. Dept. of Physiological Sciences.
    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 Cycle and oxidative phosphorylation (Lopaschuk, 1998). Therefore, 30 mM acetate (Ac) may hypothetically provide protection similar to 10 mM Glu providing that there is residual oxygen 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 the consequences of ischaemia were minimal, to determine whether the protective effects of Glu and. Ac is oxygen dependent, and to investigate whether equi-carbon concentrations of Ac and Giu would offer similar protection during low flow ischaemia. Materials and Methods: 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 5 mM or 10 mM or 30 mM Ac or 10 mM Glu. Additional hearts were subjected to anoxia during the same period. All hearts were reperfused for 30 minutes under the preischaemic conditions. We measured the time to the onset of ischaemic contracture (TOIC), the percentage recovery of left ventricular developed pressure (L VDP), and tissue ATP, creatine phosphate, lactate, glycogen and cAMP content. Results: 5 mM and 10 mM Ac perfused hearts yielded optimal yet similar protection against the consequences of ischaemia. In addition, Ac (5 mM) and Glu (10 mM) treated hearts performed equally poorly in the absence of oxygen. This implies that the beneficial effects conferred by Glu is oxygen dependent, due possibly to the activity of the Krebs Cycle and oxidative phosphorylation. An equi-carbon concentration of Ac (30 mM) could not offer protection analogous to 10 mM Glu during oxygenated, low flow ischaemic conditions. Instead, 10 mM Glu provided optimal protection against ischaemia while 30 mM Ac was associated with accelerated TOIC, reduced ATP and glycogen levels, elevated lactate and· cAMP levels, and weakened function upon reperfusion. Conclusion: Glu provided maximal protection against the consequences of low flow ischaemia. However, this protection was dependent on the availability of oxygen, suggesting that oxidative phosphorylation and Krebs Cycle activity may contribute more to the protective effects of a particular substrate than previously anticipated.