Serum Metabolomics Reveals Distinct Profiles during Ischemia and Reperfusion in a Porcine Model of Myocardial Ischemia-Reperfusion

Acute myocardial infarction (MI) is one of the leading causes of death worldwide. Early identification of ischemia and establishing reperfusion remain cornerstones in the treatment of MI, as mortality and morbidity can be significantly reduced by establishing reperfusion to the affected areas. The aim of the current study was to investigate the metabolomic changes in the serum in a swine model of MI induced by ischemia and reperfusion (I/R) injury, and to identify circulating metabolomic biomarkers for myocardial injury at different phases. Female Yucatan minipigs were subjected to 60 min of ischemia followed by reperfusion, and serum samples were collected at baseline, 60 min of ischemia, 4 h of reperfusion, and 24 h of reperfusion. Circulating metabolites were analyzed using an untargeted metabolomic approach. A bioinformatic approach revealed that serum metabolites show distinct profiles during ischemia and during early and late reperfusion. Some notable changes during ischemia include accumulation of metabolites that indicate impaired mitochondrial function and N-terminally modified amino acids. Changes in branched-chain amino-acid metabolites were noted during early reperfusion, while bile acid pathway derivatives and intermediates predominated in the late reperfusion phases. This indicates a potential for such an approach toward identification of the distinct phases of ischemia and reperfusion in clinical situations.

Automated summary

Acute myocardial infarction is a leading cause of death worldwide. This study investigated the metabolic changes in serum during ischemia and reperfusion injury in a swine model, aiming to identify metabolomic biomarkers for myocardial injury at different phases. The results showed distinct profiles of serum metabolites during ischemia and early and late reperfusion, with impaired mitochondrial function and amino acid modifications during ischemia, and changes in branched-chain amino acid metabolites and bile acid pathway derivatives during reperfusion.