Plasma metabolomics supports the use of long-duration cardiac arrest rodent model to study human disease by demonstrating similar metabolic alterations

Abstract

Cardiac arrest (CA) is a leading cause of death and there is a necessity for animal models that accurately represent human injury severity. We evaluated a rat model of severe CA injury by comparing plasma metabolic alterations to human patients. Plasma was obtained from adult human control and CA patients post-resuscitation, and from male Sprague–Dawley rats at baseline and after 20 min CA followed by 30 min cardiopulmonary bypass resuscitation. An untargeted metabolomics evaluation using UPLC-QTOF-MS/MS was performed for plasma metabolome comparison. Here we show the metabolic commonality between humans and our severe injury rat model, highlighting significant metabolic dysfunction as seen by similar alterations in (1) TCA cycle metabolites, (2) tryptophan and kynurenic acid metabolites, and (3) acylcarnitine, fatty acid, and phospholipid metabolites. With substantial interspecies metabolic similarity in post-resuscitation plasma, our long duration CA rat model metabolically replicates human disease and is a suitable model for translational CA research.