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The nucleotide metabolism in lactate perfused hearts under ischaemic and reperfused conditions

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Abstract

It was examined whether lactate influences postischaemic hemodynamic recovery as a function of the duration of ischaemia and whether changes in high-energy phosphate metabolism under ischaemic and reperfused conditions could be held responsible for impairment of cardiac function. To this end, isolated working rat hearts were perfused with either glucose (11 mM), glucose (11 mM) plus lactate (5 mM) or glucose (11 mM) plus pyruvate (5 mM). The extent of ischaemic injury was varied by changing the intervals of ischaemia, i.e. 15, 30 and 45 min. Perfusion by lactate evoked marked depression of functional recovery after 30 min of ischaemia. Perfusion by pyruvate resulted in marked decline of cardiac function after 45 min of ischaemia, while in glucose perfused hearts hemodynamic performance was still recovered to some extent after 45 min of ischaemia. Hence, lactate accelerates postischaemic hemodynamic impairment compared to glucose and pyruvate. The marked decline in functional recovery of the lactate perfused hearts cannot be ascribed to the extent of degradation of high-energy phosphates during ischaemia as compared to glucose and pyruvate perfused hearts. Glycolytic ATP formation (evaluated by the rate of lactate production) can neither be responsible for loss of cardiac function in the lactate perfused hearts. Moreover, failure of reenergization during reperfusion, the amount of nucleosides and oxypurines lost or the level of high-energy phosphates at the end of reperfusion cannot explain lactate-induced impairment. Alternatively, the accumulation of endogenous lactate may have contributed to ischaemic damage in the lactate perfused hearts after 30 min of ischaemia as it was higher in the lactate than in the glucose or pyruvate perfused hearts. It cannot be excluded that possible beneficial effects of the elevated glycolytic ATP formation during 15 to 30 min of ischaemia in the lactate perfused hearts are counterbalanced by the detrimental effects of lactate accumulation.

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Authors and Affiliations

  1. Department of Physiology, Cardiovascular Research Institute Maastricht, University of Limburg, Postbus 616, 6200, MD Maastricht, The Netherlands

    Monique J. M. de Groot, Will A. Coumans & Ger J. van der Vusse

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  1. Monique J. M. de Groot
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  2. Will A. Coumans
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  3. Ger J. van der Vusse
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de Groot, M.J.M., Coumans, W.A. & van der Vusse, G.J. The nucleotide metabolism in lactate perfused hearts under ischaemic and reperfused conditions. Mol Cell Biochem 118, 1–14 (1992). https://doi.org/10.1007/BF00249689

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  • DOI: https://doi.org/10.1007/BF00249689

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