Lipoamide influences substrate selection in post-ischaemic perfused rat hearts

Abstract

We investigated whether lipoamide and diacetyl-lipoamide are able to change the substrate selection in post-ischaemic myocardium. This can be important, because shifting heart metabolism from fatty acid to carbohydrate oxidation can decrease ischaemic injury. Studying the metabolism of [1,2-13C]diacetyl-lipoamide in situ in perfused rat heart by 13C n.m.r., we found intense 13C labelling in glutamate and aspartate, showing that acetyl groups from diacetyl-lipoamide are effectively transferred to CoA and metabolized in heart tissue. From analysis of glutamate C-3 and C-4 isotopomers, we determined the [1,2-13C]acetate/[3-13C]lactate utilization ratio in normoxic and post-ischaemic hearts, where under our experimental conditions the acetate/lactate utilization 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 is almost equal to that found for normoxic hearts, showing that lipoamide increased the lactate utilization. In accordance with these data, we found that lipoamide activated pyruvate dehydrogenase by 50% in post-ischaemic myocardium. Competition between [3-13C]lactate and unlabelled octanoate was also studied in post-ischaemic hearts, and we found that lipoamide increased lactate utilization by 100% and increased the rate of the tricarboxylic acid cycle by 64%. Under the same experimental conditions, lipoamide significantly promoted the recovery of post-ischaemic unpaced hearts, showing the positive effect of increased lactate oxidation in post-ischaemic myocardium.