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Background: Multicapillary column ion-mobility spectrometry (MCC-IMS) may identify volatile components in exhaled gas. The authors therefore used MCC-IMS to evaluate exhaled gas in a rat model of sepsis, inflammation, and hemorrhagic shock.
Methods: Male Sprague-Dawley rats were anesthetized and ventilated via tracheostomy for 10 h or until death. Sepsis was induced by cecal ligation and incision in 10 rats; a sham operation was performed in 10 others. In 10 other rats, endotoxemia was induced by intravenous administration of 10 mg/kg lipopolysaccharide. In a final 10 rats, hemorrhagic shock was induced to a mean arterial pressure of 35 +/- 5 mmHg. Exhaled gas was analyzed with MCC-IMS, and volatile compounds were identified using the BS-MCC/IMS-analytes database (Version 1209; B&S Analytik, Dortmund, Germany).
Results: All sham animals survived the observation period, whereas mean survival time was 7.9 h in the septic animals, 9.1 h in endotoxemic animals, and 2.5 h in hemorrhagic shock. Volatile compounds showed statistically significant differences in septic and endotoxemic rats compared with sham rats for 3-pentanone and acetone. Endotoxic rats differed significantly from sham for 1-propanol, butanal, acetophenone, 1,2-butandiol, and 2-hexanone. Statistically significant differences were observed between septic and endotoxemic rats for butanal, 3-pentanone, and 2-hexanone. 2-Hexanone differed from all other groups in the rats with shock.
Conclusions: Breath analysis of expired organic compounds differed significantly in septic, inflammation, and sham rats. MCC-IMS of exhaled breath deserves additional study as a noninvasive approach for distinguishing sepsis from inflammation.
Influence of the respirator on volatile organic compounds : an animal study in rats over 24 hours
(2015)
Long-term animal studies are needed to accomplish measurements of volatile organic compounds (VOCs) for medical diagnostics. In order to analyze the time course of VOCs, it is necessary to ventilate these animals. Therefore, a total of 10 male Sprague–Dawley rats were anaesthetized and ventilated with synthetic air via tracheotomy for 24 h. An ion mobility spectrometry coupled to multi-capillary columns (MCC–IMS) was used to analyze the expired air. To identify background contaminations produced by the respirator itself, six comparative measurements were conducted with ventilators only. Overall, a number of 37 peaks could be detected within the positive mode. According to the ratio peak intensity rat/ peak intensity ventilator blank, 22 peaks with a ratio >1.5 were defined as expired VOCs, 12 peaks with a ratio between 0.5 and 1.5 as unaffected VOCs, and three peaks with a ratio <0.5 as resorbed VOCs. The peak intensity of 12 expired VOCs changed significantly during the 24 h measurement. These results represent the basis for future intervention studies. Notably, online VOC analysis with MCC–IMS is possible over 24 h in ventilated rats and allows different experimental approaches.
In breath analysis, ambient air contaminations are ubiquitous and difficult to eliminate. This study was designed to investigate the reduction of ambient air background by a lung wash-out with synthetic air. The reduction of the initial ambient air volatile organic compound (VOC) intensity was investigated in the breath of 20 volunteers inhaling synthetic air via a sealed full face mask in comparison to inhaling ambient air. Over a period of 30 minutes, breath analysis was conducted using ion mobility spectrometry coupled to a multi-capillary column. A total of 68 VOCs were identified for inhaling ambient air or inhaling synthetic air. By treatment with synthetic air, 39 VOCs decreased in intensity, whereas 29 increased in comparison to inhaling ambient air. In total, seven VOCs were significantly reduced (P-value < 0.05). A complete wash-out of VOCs in this setting was not observed, whereby a statistically significant reduction up to 65% as for terpinolene was achieved. Our setting successfully demonstrated a reduction of ambient air contaminations from the airways by a lung wash-out with synthetic air.
Rats are commonly used in medical research as they enable a high grade of standardization. The exhalome of ventilated rats has not as yet been investigated using an ion mobility spectrometer coupled with a multi-capillary column (MCC-IMS). As a first step, a rat model has to be established to measure potential biomarkers in the exhale with long-term settings, allowing constant and continuous analysis of exhaled air in time series. Therefore, eight animals were anaesthetized, prepared and ventilated for 1 h. A total of 73 peaks were directly detected with the IMS chromatogram. Thirty five of them were assigned to the ventilator system and 38 to the animals. Peak intensity varied within three measurements. The intensity of analytes of individual rats varied by a factor of up to 18. This new model will also enable continuous measurements of volatile organic compounds (VOCs) from rat's breath in long-term experiments. It is hoped that, in the future, variability and progression of VOCs can be monitored in different models of diseases using this set-up.