Blood microsampling for untargeted metabolomics: a preliminary study on patients affected by myocardial infarction

Blood microsampling is a promising tool for blood collection as it is simple and minimally invasive. It allows multiple sampling and is optimal for longitudinal studies1. For these reasons, it has gained attention and has been applied to metabolomics studies. Physical activity induces metabolic changes and a correlation between metabolism and cardiovascular risk has been demonstrated. For example, physical exercise has been shown to improve the catabolism of branched-chain amino acids (BCAA)2. The involvement of BCAA in ischemic cardiomyopathy is well known: their plasma levels correlate with the presence and severity of the disease3. In this preliminary study, blood samples were collected with Dried Blood Spots (DBS) from patients affected by myocardial infarction participating in a physical rehabilitation program. Blood was collected at 7 time points: before the start of the rehabilitation protocol, before and after the first training, before and after training halfway through the rehabilitation protocol, and before and after the last training. Untargeted metabolomic analysis was performed to assess exercise-induced changes, correlation with clinical outcome and cardiovascular risk factors in these patients. Polar metabolite analysis was performed on DBS with UHPLC-MS. The results showed the most altered metabolic pathways were associated with purine metabolism and histidine metabolism. In particular, xanthine and histidine levels were high at the beginning of rehabilitation and gradually decreased with the training time. Comparing the metabolic phenotype at the beginning and at the end of rehabilitation highlighted a reduction of xanthine, urocanic acid and C5-carnitine. Overall, the use of DBS simplified longitudinal blood sampling and allowed the investigation of metabolic changes during the physical rehabilitation program after myocardial infarction.