The effects of aspartate and 2-oxoglutarate upon glycolytic energy metabolites and mechanical recovery following global ischaemia in isolated rat hearts.
The hypothesis that aspartate and 2-oxoglutarate might help to relieve the inhibition of glycolysis during global myocardial ischaemia and improve post-ischaemic mechanical recovery was tested in isolated rat hearts. The hearts were attached to a lumped parameter model of the rat vascular impedance and initially perfused in the working mode with buffered Krebs-Henseleit solution containing 10.1 mmol/l glucose, with or without 3.3 mmol/l of aspartate and 3.3 mmol/l of 2-oxoglutarate, prior to imposing global ischaemia for 5, 10 or 15 mins. The addition of aspartate and 2-oxoglutarate improved the preservation of tissue CP after 5 mins of ischaemia and of ATP after 10 mins of ischaemia. The total adenine nucleotide pool was higher in the supplemented hearts after all three periods of ischaemia. Dihydroxyacetone phosphate, alanine, succinate and lactate accumulated during ischaemia, but the dihydroxyacetone phosphate accumulation was reduced while the alanine and succinate concentrations were increased by the addition of aspartate and 2-oxoglutarate to the perfusate. These observations lend support to the hypothesis that ischaemia arrests glycolysis at the glyceraldehyde phosphate dehydrogenase step due to a lack of oxidised nicotinamide adenine dinucleotide. Increasing the substrate concentrations of aspartate and 2-oxoglutarate may permit glycolysis to proceed for longer into the period of ischaemia by stimulating an additional pathway for nicotinamide adenine dinucleotide reoxidation. Small improvements in mechanical recovery were associated with the metabolic changes.
Snaith
C D
CD
Department of Biological Sciences, University of Keele, Staffordshire, U.K.
Wright
G
G
Lofkin
M
M
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D006019:Glycolysis / Q000187:drug effects; D066298:In Vitro Techniques; D007656:Ketoglutaric Acids / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000227:Adenine Nucleotides; D007656:Ketoglutaric Acids; D010725:Phosphocreatine; D001224:Aspartic Acid