Abstract

Systemic inflammation alters the composition of exhaled breath, possibly helping clinicians diagnose conditions such as sepsis. We therefore evaluated changes in exhaled breath of rats given tumor necrosis factor-alpha (TNF-α). Thirty male Sprague-Dawley rats were randomly assigned to three groups (n = 10 each) with intravenous injections of normal saline (control), 200 µg·kg−1 bodyweight TNF-α (TNF-α-200), or 600 µg·kg−1 bodyweight TNF-α (TNF-α-600), and were observed for 24 h or until death. Animals were ventilated with highly-purified synthetic air to analyze exhaled air by multicapillary column–ion mobility spectrometry. Volatile organic compounds (VOCs) were identified from a database. We recorded blood pressure and cardiac output, along with cytokine plasma concentrations. Control rats survived the 24 h observation period, whereas mean survival time decreased to 22 h for TNF-α-200 and 23 h for TNF-α-600 rats. Mean arterial pressure decreased in TNF-α groups, whereas IL-6 increased, consistent with mild to moderate inflammation. Hundreds of VOCs were detected in exhalome. P-cymol increased by a factor-of-two 4 h after injection of TNF-α-600 compared to the control and TNF-α-200. We found that 1-butanol and 1-pentanol increased in both TNF-α groups after 20 h compared to the control. As breath analysis distinguishes between two doses of TNF-α and none, we conclude that it might help clinicians identify systemic inflammation.

Highlights

  • Inflammation is a complex biological response to infectious and non-infectious stimuli [1].Detection is difficult, because symptoms are non-specific and highly variable

  • TNF-α is an especially important cytokine in sepsis and other inflammatory conditions and of TNF-α provokes specific changes in the exhalome of rats that might be diagnostic for sepsis and promotes changings in various metabolic pathways

  • Our experimental model of systemic inflammation was based on previous work by Tracey et al [14]

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Summary

Introduction

Inflammation is a complex biological response to infectious and non-infectious stimuli [1]. Exhaled gases are potential diagnostic tools for lung cancer [5,6,7], allows detecting gastric cancer, differentiating stages of precancerous gastric lesions [10], and helps chronic obstructive pulmonary disease [8], and hemorrhagic shock [9]. The authors chromatography/mass spectrometry (SPME-GC/MS) and concluded that IMS might be a useful distinguished treatment and control animals using IMS and solid phase microextraction-gas point-of-care tool for detection of inflammation [12]. Changes in exhaled volatile organic compounds chromatography/mass spectrometry (SPME-GC/MS) and concluded that IMS might be a useful (VOCs) have been used to detect polymicrobial sepsis and inflammation in rats [13]. TNF-α is an especially important cytokine in sepsis and other inflammatory conditions and of TNF-α provokes specific changes in the exhalome of rats that might be diagnostic for sepsis and promotes changings in various metabolic pathways. Of TNF-α provokes specific changes in the exhalome of rats that might be diagnostic for sepsis and inflammation

Survival
Blood Gas Analysis
Multicapillary Column Ion-Mobility Spectrometry in Rats
Discussion
Animals
Surgical Procedures of Experimental Animals
Experimental Protocol
MCC-IMS Measurement
Cytokine Assay
Data Processing and Statistical Analysis

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