Biochemical mechanism of infarct size reduction by pyruvate

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Abstract
We have explored the biochemical mechanism of the infarct size reduction found after intracoronary pyruvate infusion. Using the double infarct model, we simultaneously produced in nine dogs a control- and a therapy-infarct and compared the infarct sizes in each dog after 90 min of occlusion and 90 min of reflow. Intracoronary pyruvate reached the therapy infarct only by way of collaterals but had no access to the control infarct. Tissue levels of reduced nicotinamide dinucleotide (NADH) were measured in control-normal-, therapy-normal-, control-ischaemic-and pyruvate-treated ischaemic areas. In all nine dogs we found a significant reduction in infarct size and NADH levels in the pyruvate-treated areas. Therapy-normal NADH levels fell to 30 ± l0% (mean ± SD) of control-normal levels and therapy-ischaemic NADH levels to 26 ± 17% of control-ischaemic levels. We assumed that the infused pyruvate was converted to lactate and at the same time NAD was generated from NADH. Thereby the blockade of glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) by high NADH/NAD-ratios in ischaemic myocardium should be moderated, and ATP production by anaerobic glycolysis stimulated. These small amounts of ATP may be sufficient to guarantee membrane integrity over 90 min of ischaemia and so diminish its harmful effects on the myocardium.