The Metabolopathy of Tissue Injury, Hemorrhagic Shock, and Resuscitation in a Rat Model

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Abstract

Introduction:

The metabolic consequences of trauma induce significant clinical pathology. In this study, we evaluate the independent, metabolic contributions of tissue injury (TI) and combined tissue injury and hemorrhagic shock (TI/HS) using mass spectrometry (MS) metabolomics in a controlled animal model of critical injury.

Methods:

Sprague–Dawley rats (n = 14) underwent TI alone or TI/HS, followed by resuscitation with normal saline and shed blood. Plasma was collected (baseline, post-laparotomy, post-HS, post-resuscitation) for ultra-high pressure liquid chromatography MS-metabolomics. Repeated-measures ANOVA with Tukey multiple column comparison test compared the fold change of metabolite concentration among the animal groups at corresponding time points.

Results:

Four hundred forty metabolites were identified. TI alone did not change the metabolite levels versus baseline. TI/HS induced changes in metabolites from glycolysis, the tricarboxylic acid cycle, the pentose phosphate, fatty acid and glutathione homeostasis pathways, sulfur metabolism, and urea cycle versus TI alone. Following resuscitation many metabolites normalized to TI alone levels, including lactate, most tri-carboxylic acid metabolites, most urea cycle metabolites, glutathione disulfide, and some metabolites from both the pentose phosphate pathway and sulfur metabolism.

Conclusions:

Significant changes occur immediately following TI/HS versus TI alone. These metabolic changes are not explained by dilution as a number of metabolites remained unchanged or even increased following resuscitation. The differential metabolic changes resulting from TI alone and TI/HS provide foundation for future investigations severe injury in humans, where TI and HS are often concurrent. This investigation provides a foundation to evaluate metabolic-related outcomes and design-targeted resuscitation strategies.

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