Tissue‐Specific Metabolic Profiles After Prolonged Cardiac Arrest Reveal Brain Metabolome Dysfunction Predominantly After Resuscitation

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Abstract
Background: Cardiac arrest (CA) has been a leading cause of death for many decades. Despite years of research, we still do not understand how each organ responds to the reintroduction of blood flow after prolonged CA. Following changes in metabolites of individual organs after CA and resuscitation gives context to the efficiency and limitations of current resuscitation protocols. Methods and Results: Adult male Sprague–Dawley rats were arbitrarily assigned into 3 groups: control, 20 minutes of CA, or 20 minutes of CA followed by 30 minutes of cardiopulmonary bypass resuscitation. The rats were euthanized by decapitation to harvest brain, heart, kidney, and liver tissues. The obtained tissue samples were analyzed by ultra‐high‐performance liquid chromatography–high‐accuracy mass spectrometry for comprehensive metabolomics evaluation. After resuscitation, the brain showed decreased glycolysis metabolites and fatty acids and increased amino acids compared with control. Similarly, the heart displayed alterations mostly in amino acids. The kidney showed decreased amino acid and fatty acid pools with severely increased tricarboxylic acid cycle metabolites following resuscitation, while the liver showed minimal alterations with slight changes in the lipid pool. Each tissue has a distinct pattern of metabolite changes after ischemia/reperfusion. Furthermore, resuscitation worsens the metabolic dysregulation in the brain and kidney, while it normalizes metabolism in the heart. Conclusions: Developing metabolic profiles using a global metabolome analysis identifies the variable nature of metabolites in individual organs after CA and reperfusion, establishing a stark contrast between the normalized heart and liver and the exacerbated brain and kidney, only after the reestablishment of blood circulation.

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