Ex Vivo Lung Perfusion with β-Nicotinamide Adenine Dinucleotide (NAD<sup>+</sup>) Improves Ischemic Lung Function
Ischemia-reperfusion injury compromises short- and long-term outcomes after lung transplantation. The scarce existing data on NAD<sup>+</sup> suggest effects on hypoxia-induced vasoconstriction, on reactive oxygen species and on tampering inflammation. We exposed rat lungs to 14 h of col...
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| Format: | Article |
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MDPI AG
2022-04-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/5/843 |
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| author | Jonas Peter Ehrsam Jin Chen Hector Rodriguez Cetina Biefer Isabelle Opitz Stephan Arni Ilhan Inci |
| author_facet | Jonas Peter Ehrsam Jin Chen Hector Rodriguez Cetina Biefer Isabelle Opitz Stephan Arni Ilhan Inci |
| author_sort | Jonas Peter Ehrsam |
| collection | DOAJ |
| description | Ischemia-reperfusion injury compromises short- and long-term outcomes after lung transplantation. The scarce existing data on NAD<sup>+</sup> suggest effects on hypoxia-induced vasoconstriction, on reactive oxygen species and on tampering inflammation. We exposed rat lungs to 14 h of cold ischemic storage and perfused them in a rat ex vivo lung perfusion (EVLP) system for 4 h. A control group (<i>n</i> = 6) was compared to groups receiving 100 µM (<i>n</i> = 6) or 200 µM NAD<sup>+</sup> (<i>n</i> = 6) in the preservation solution and groups receiving 200 µM (<i>n</i> = 4) or 2000 µM (<i>n</i> = 6) NAD<sup>+</sup> every 30 min in the perfusate, starting at 1 h of EVLP. Compared to the control, significant effects were only achieved in the 2000 µM NAD<sup>+</sup> group. During the 4 h of EVLP, we monitored higher vascular flow, lower mean pulmonary arterial pressure and increased oxygenation capacity. Tissue inflammation estimated with the myeloperoxidase assay was lower in the 2000 µM NAD<sup>+</sup> group. We observed higher levels of anti-inflammatory IL-10, higher anti-inflammatory IL-6/IL-10 ratios and lower levels of pro-inflammatory IL-12 and IL-18 as well as a trend of more anti-inflammatory IFNy in the 2000 µM NAD<sup>+</sup> perfusate. In the bronchoalveolar lavage, the pro-inflammatory levels of IL-1α and IL-1β were lower in the 2000 µM NAD<sup>+</sup> group. NAD<sup>+</sup> administered during EVLP is a promising agent with both anti-inflammatory properties and the ability to improve ischemic lung function. |
| first_indexed | 2024-03-10T03:26:16Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T03:26:16Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-54023dc6c34b488ba8af6f64987176252023-11-23T09:50:38ZengMDPI AGAntioxidants2076-39212022-04-0111584310.3390/antiox11050843Ex Vivo Lung Perfusion with β-Nicotinamide Adenine Dinucleotide (NAD<sup>+</sup>) Improves Ischemic Lung FunctionJonas Peter Ehrsam0Jin Chen1Hector Rodriguez Cetina Biefer2Isabelle Opitz3Stephan Arni4Ilhan Inci5Department of Thoracic Surgery, University Hospital Zurich, 8091 Zurich, SwitzerlandDepartment of Thoracic Surgery, University Hospital Zurich, 8091 Zurich, SwitzerlandDepartment of Cardiac Surgery, City Hospital of Zurich, 8063 Zurich, SwitzerlandDepartment of Thoracic Surgery, University Hospital Zurich, 8091 Zurich, SwitzerlandDepartment of Thoracic Surgery, University Hospital Zurich, 8091 Zurich, SwitzerlandDepartment of Thoracic Surgery, University Hospital Zurich, 8091 Zurich, SwitzerlandIschemia-reperfusion injury compromises short- and long-term outcomes after lung transplantation. The scarce existing data on NAD<sup>+</sup> suggest effects on hypoxia-induced vasoconstriction, on reactive oxygen species and on tampering inflammation. We exposed rat lungs to 14 h of cold ischemic storage and perfused them in a rat ex vivo lung perfusion (EVLP) system for 4 h. A control group (<i>n</i> = 6) was compared to groups receiving 100 µM (<i>n</i> = 6) or 200 µM NAD<sup>+</sup> (<i>n</i> = 6) in the preservation solution and groups receiving 200 µM (<i>n</i> = 4) or 2000 µM (<i>n</i> = 6) NAD<sup>+</sup> every 30 min in the perfusate, starting at 1 h of EVLP. Compared to the control, significant effects were only achieved in the 2000 µM NAD<sup>+</sup> group. During the 4 h of EVLP, we monitored higher vascular flow, lower mean pulmonary arterial pressure and increased oxygenation capacity. Tissue inflammation estimated with the myeloperoxidase assay was lower in the 2000 µM NAD<sup>+</sup> group. We observed higher levels of anti-inflammatory IL-10, higher anti-inflammatory IL-6/IL-10 ratios and lower levels of pro-inflammatory IL-12 and IL-18 as well as a trend of more anti-inflammatory IFNy in the 2000 µM NAD<sup>+</sup> perfusate. In the bronchoalveolar lavage, the pro-inflammatory levels of IL-1α and IL-1β were lower in the 2000 µM NAD<sup>+</sup> group. NAD<sup>+</sup> administered during EVLP is a promising agent with both anti-inflammatory properties and the ability to improve ischemic lung function.https://www.mdpi.com/2076-3921/11/5/843ex vivo lung perfusionlung transplantationlung donationnicotinamide adenine dinucleotideoxidative stressischemia |
| spellingShingle | Jonas Peter Ehrsam Jin Chen Hector Rodriguez Cetina Biefer Isabelle Opitz Stephan Arni Ilhan Inci Ex Vivo Lung Perfusion with β-Nicotinamide Adenine Dinucleotide (NAD<sup>+</sup>) Improves Ischemic Lung Function Antioxidants ex vivo lung perfusion lung transplantation lung donation nicotinamide adenine dinucleotide oxidative stress ischemia |
| title | Ex Vivo Lung Perfusion with β-Nicotinamide Adenine Dinucleotide (NAD<sup>+</sup>) Improves Ischemic Lung Function |
| title_full | Ex Vivo Lung Perfusion with β-Nicotinamide Adenine Dinucleotide (NAD<sup>+</sup>) Improves Ischemic Lung Function |
| title_fullStr | Ex Vivo Lung Perfusion with β-Nicotinamide Adenine Dinucleotide (NAD<sup>+</sup>) Improves Ischemic Lung Function |
| title_full_unstemmed | Ex Vivo Lung Perfusion with β-Nicotinamide Adenine Dinucleotide (NAD<sup>+</sup>) Improves Ischemic Lung Function |
| title_short | Ex Vivo Lung Perfusion with β-Nicotinamide Adenine Dinucleotide (NAD<sup>+</sup>) Improves Ischemic Lung Function |
| title_sort | ex vivo lung perfusion with β nicotinamide adenine dinucleotide nad sup sup improves ischemic lung function |
| topic | ex vivo lung perfusion lung transplantation lung donation nicotinamide adenine dinucleotide oxidative stress ischemia |
| url | https://www.mdpi.com/2076-3921/11/5/843 |
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