PMID- 33929393 OWN - NLM STAT- MEDLINE DCOM- 20210727 LR - 20230721 IS - 1526-7598 (Electronic) IS - 0003-2999 (Linking) VI - 133 IP - 1 DP - 2021 Jul 1 TI - Volutrauma Increases Exhaled Pentanal in Rats: A Potential Breath Biomarker for Ventilator-Induced Lung Injury. PG - 263-273 LID - 10.1213/ANE.0000000000005576 [doi] AB - BACKGROUND: Mechanical ventilation injures lungs, but there are currently no reliable methods for detecting early injury. We therefore evaluated whether exhaled pentanal, a lipid peroxidation product, might be a useful breath biomarker for stretch-induced lung injury in rats. METHODS: A total of 150 male Sprague-Dawley rats were investigated in 2 substudies. The first randomly assigned 75 rats to 7 hours of mechanical ventilation at tidal volumes of 6, 8, 12, 16, and 20 mL.kg-1. The second included 75 rats. A reference group was ventilated at a tidal volume of 6 mL.kg-1 for 10 hours 4 interventional groups were ventilated at a tidal volume of 6 mL.kg-1 for 1 hour, and then for 0.5, 1, 2, or 3 hours at a tidal volume of 16 mL.kg-1 before returning to a tidal volume of 6 mL.kg-1 for additional 6 hours. Exhaled pentanal was monitored by multicapillary column-ion mobility spectrometry. The first substudy included cytokine and leukocyte measurements in blood and bronchoalveolar fluid, histological assessment of the proportion of alveolar space, and measurements of myeloperoxidase activity in lung tissue. The second substudy included measurements of pentanal in arterial blood plasma, cytokine and leukocyte concentrations in bronchoalveolar fluid, and cleaved caspase 3 in lung tissue. RESULTS: Exhaled pentanal concentrations increased by only 0.5 ppb.h-1 (95% confidence interval [CI], 0.3-0.6) when rats were ventilated at 6 mL.kg-1. In contrast, exhaled pentanal concentrations increased substantially and roughly linearly at higher tidal volumes, up to 3.1 ppb.h-1 (95% CI, 2.3-3.8) at tidal volumes of 20 mL.kg-1. Exhaled pentanal increased at average rates between 1.0 ppb.h-1 (95% CI, 0.3-1.7) and 2.5 ppb.h-1 (95% CI, 1.4-3.6) after the onset of 16 mL.kg-1 tidal volumes and decreased rapidly by a median of 2 ppb (interquartile range [IQR], 0.9-3.2), corresponding to a 38% (IQR, 31-43) reduction when tidal volume returned to 6 mL.kg-1. Tidal volume, inspiratory pressure, and mechanical power were positively associated with pentanal exhalation. Exhaled and plasma pentanal were uncorrelated. Alveolar space decreased and inflammatory markers in bronchoalveolar lavage fluid increased in animals ventilated at high tidal volumes. Short, intermittent ventilation at high tidal volumes for up to 3 hours increased neither inflammatory markers in bronchoalveolar fluid nor the proportion of cleaved caspase 3 in lung tissue. CONCLUSIONS: Exhaled pentanal is a potential biomarker for early detection of ventilator-induced lung injury in rats. CI - Copyright (c) 2021 International Anesthesia Research Society. FAU - Muller-Wirtz, Lukas Martin AU - Muller-Wirtz LM AD - From the CBR - Center of Breath Research, Department of Anaesthesiology, Intensive Care and Pain Therapy, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Germany. FAU - Kiefer, Daniel AU - Kiefer D AD - From the CBR - Center of Breath Research, Department of Anaesthesiology, Intensive Care and Pain Therapy, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Germany. FAU - Maurer, Felix AU - Maurer F AD - From the CBR - Center of Breath Research, Department of Anaesthesiology, Intensive Care and Pain Therapy, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Germany. FAU - Floss, Maximilian Alexander AU - Floss MA AD - From the CBR - Center of Breath Research, Department of Anaesthesiology, Intensive Care and Pain Therapy, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Germany. FAU - Doneit, Jonas AU - Doneit J AD - From the CBR - Center of Breath Research, Department of Anaesthesiology, Intensive Care and Pain Therapy, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Germany. FAU - Huppe, Tobias AU - Huppe T AD - From the CBR - Center of Breath Research, Department of Anaesthesiology, Intensive Care and Pain Therapy, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Germany. FAU - Shopova, Theodora AU - Shopova T AD - From the CBR - Center of Breath Research, Department of Anaesthesiology, Intensive Care and Pain Therapy, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Germany. FAU - Wolf, Beate AU - Wolf B AD - From the CBR - Center of Breath Research, Department of Anaesthesiology, Intensive Care and Pain Therapy, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Germany. FAU - Sessler, Daniel I AU - Sessler DI AD - Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio. FAU - Volk, Thomas AU - Volk T AD - From the CBR - Center of Breath Research, Department of Anaesthesiology, Intensive Care and Pain Therapy, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Germany. FAU - Kreuer, Sascha AU - Kreuer S AD - From the CBR - Center of Breath Research, Department of Anaesthesiology, Intensive Care and Pain Therapy, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Germany. FAU - Fink, Tobias AU - Fink T AD - From the CBR - Center of Breath Research, Department of Anaesthesiology, Intensive Care and Pain Therapy, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Anesth Analg JT - Anesthesia and analgesia JID - 1310650 RN - 0 (Aldehydes) RN - 0 (Anesthetics, Inhalation) RN - 0 (Biomarkers) RN - 38LVP0K73A (Sevoflurane) RN - B975S3014W (pentanal) SB - IM MH - Aldehydes/analysis/*metabolism MH - Anesthetics, Inhalation/administration & dosage MH - Animals MH - Biomarkers/metabolism MH - Bronchoalveolar Lavage Fluid/chemistry MH - Exhalation/drug effects/*physiology MH - Male MH - Rats MH - Rats, Sprague-Dawley MH - Respiration, Artificial/*adverse effects MH - Sevoflurane/administration & dosage MH - Tidal Volume/drug effects/physiology MH - Ventilator-Induced Lung Injury/etiology/*metabolism COIS- The authors declare no conflicts of interest. EDAT- 2021/05/01 06:00 MHDA- 2021/07/28 06:00 CRDT- 2021/04/30 12:18 PHST- 2021/05/01 06:00 [pubmed] PHST- 2021/07/28 06:00 [medline] PHST- 2021/04/30 12:18 [entrez] AID - 00000539-202107000-00033 [pii] AID - 10.1213/ANE.0000000000005576 [doi] PST - ppublish SO - Anesth Analg. 2021 Jul 1;133(1):263-273. doi: 10.1213/ANE.0000000000005576.