Abstract Body (Do not enter title and authors here): Introduction. Lactic acid is increasingly recognized as an alternative fuel source for various tissues, including the brain and heart. It is acknowledged as a protective compound in tissues such as the brain, particularly under conditions like traumatic brain injury or ischemia-reperfusion. However, its potential as a cardioprotective agent remains controversial.
Aims. We aimed to (1) evaluate the impact of acute L-lactic acid administration at reperfusion onset on myocardial infarct size in isolated mouse hearts after transient global ischemia, and (2) elucidate the underlying mechanisms.
Methods. Isolated mouse hearts underwent 35 min global ischaemia followed by 60 min of reperfusion and were randomly assigned to experimental groups. Control hearts (n=7) received standard Krebs buffer, while L-lactic acid-treated hearts received Krebs containing 8 or 20 mmol/L L-lactic acid for the first 15 minutes of reperfusion (n=5). To assess the contribution of acidosis to the observed effects, 5 hearts were treated with acidic Krebs (pH 7.0) for the same time period. To evaluate the role of import of L-lactic acid through monocarboxylate transporter 1 (MCT1) in those effects, additional hearts (n=6) were treated with L-lactic acid and 1 μmol/L AR-C141990 hydrochloride.
Results. L-lactic acid induced a concentration-dependent reduction in infarct size, achieving a 23% reduction at 20 mmol/L (from 44.74±2.24 to 21.46±1.93%, ANOVA and Tukey’s tests, p=0.0006). This protective effect was associated with reduced lactate dehydrogenase release and improved functional recovery during reperfusion. Perfusion with an acidic Krebs also reduced infarct size, but to a lesser extent than L-lactic acid (see Figure). MCT1 inhibition with AR-C 141990 attenuated the protective effect of L-lactic acid to the levels seen with the acidic Krebs (see Figure). ¹H NMR spectroscopy revealed significant metabolic changes in L-lactic acid-treated hearts, with pathway enrichment analysis indicating nearly a 3-fold enrichment in pyruvate metabolism, fatty acid biosynthesis, and gluconeogenesis, suggestive of a metabolic shift.
Conclusions. These findings support a cardioprotective role for L-lactic acid against ischemia-reperfusion injury, attributable to both acidosis and MCT1-mediated uptake, leading to metabolic reprogramming.