LIPOAMIDE INFLUENCES SUBSTRATE SELECTION IN POSTISCHEMIC PERFUSED RATHEARTS

We investigated whether lipoamide and diacetyl-lipoamide are able to c hange the substrate selection in post-ischaemic myocardium. This can b e important, because shifting heart metabolism from fatty acid to carb ohydrate oxidation can decrease ischaemic injury. Studying the metabol ism of [1,2-C-13]diacetyl-lipoamide in situ in perfused rat heart by C -13 n.m.r., we found intense C-13 labelling in glutamate and aspartate , showing that acetyl groups from diacetyl-lipoamide are effectively t ransferred to CoA and metabolized in heart tissue. From analysis of gl utamate C-3 and C-4 isotopomers, we determined the [1,2-C-13]acetate/[ 3-C-13]lactate utilization ratio in normoxic and postischaemic hearts, where under our experimental conditions the acetate/lactate utilizati on ratios were 1.2+/-0.2 and 2.4+/-0.3 in normoxic and post-ischaemic hearts respectively. When 0.25 mM lipoamide was added to the perfusate the acetate/lactate utilization ratio decreased to 1.4+/-0.1, which i s almost equal to that found for normoxic hearts, showing that lipoami de increased the lactate utilization. In accordance with these data, w e found that lipoamide activated pyruvate dehydrogenase by 50% in post ischaemic myocardium. Competition between [3-C-13]lactate and unlabell ed octanoate was also studied in post-ischaemic hearts, and we found t hat lipoamide increased lactate utilization by 100% and increased the rate of the tricarboxylic acid cycle by 64%. Under the same experiment al conditions, lipoamide significantly promoted the recovery of post-i schaemic unpaced hearts, showing the positive effect of increased lact ate oxidation in post-ischaemic myocardium.