A Rat Model of Clinically Relevant Extracorporeal Circulation Develops Early Organ Dysfunctions
In clinical practice, extracorporeal circulation (ECC) is associated with coagulopathy and inflammation, eventually leading to organ injuries without preventive systemic pharmacological treatment. Relevant models are needed to reproduce the pathophysiology observed in humans and preclinical tests. R...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/8/7338 |
| _version_ | 1797605097469902848 |
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| author | Antoine Persello Fouzia Souab Thomas Dupas Virginie Aillerie Edith Bigot Manon Denis Angélique Erraud Thomas Pelé Angélique Blangy-Letheule Pierre Miniou Philippe Guedat Michel De Waard Emmanuelle Abgueguen Bertrand Rozec Benjamin Lauzier |
| author_facet | Antoine Persello Fouzia Souab Thomas Dupas Virginie Aillerie Edith Bigot Manon Denis Angélique Erraud Thomas Pelé Angélique Blangy-Letheule Pierre Miniou Philippe Guedat Michel De Waard Emmanuelle Abgueguen Bertrand Rozec Benjamin Lauzier |
| author_sort | Antoine Persello |
| collection | DOAJ |
| description | In clinical practice, extracorporeal circulation (ECC) is associated with coagulopathy and inflammation, eventually leading to organ injuries without preventive systemic pharmacological treatment. Relevant models are needed to reproduce the pathophysiology observed in humans and preclinical tests. Rodent models are less expensive than large models but require adaptations and validated comparisons to clinics. This study aimed to develop a rat ECC model and to establish its clinical relevance. One hour of veno-arterial ECC or a sham procedure were achieved on mechanically ventilated rats after cannulations with a mean arterial pressure objective > 60 mmHg. Five hours post-surgery, the rats’ behavior, plasmatic/blood biomarkers, and hemodynamics were measured. Blood biomarkers and transcriptomic changes were compared in 41 patients undergoing on-pump cardiac surgery. Five hours post-ECC, the rats presented hypotension, hyperlactatemia, and behavioral alterations. The same patterns of marker measurements (Lactate dehydrogenase, Creatinine kinase, ASAT, ALAT, and Troponin T) were observed in both rats and human patients. Transcriptome analyses showed similarity in both humans and rats in the biological processes involved in the ECC response. This new ECC rat model seems to resemble both ECC clinical procedures and the associated pathophysiology, but with early organ injury corresponding to a severe phenotype. Although the mechanisms at stake in the post-ECC pathophysiology of rats or humans need to be described, this new rat model appears to be a relevant and costless preclinical model of human ECC. |
| first_indexed | 2024-03-11T04:56:19Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:56:19Z |
| publishDate | 2023-04-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9abcff36ac6d48cd9b3b6dbf00dd042a2023-11-17T19:38:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248733810.3390/ijms24087338A Rat Model of Clinically Relevant Extracorporeal Circulation Develops Early Organ DysfunctionsAntoine Persello0Fouzia Souab1Thomas Dupas2Virginie Aillerie3Edith Bigot4Manon Denis5Angélique Erraud6Thomas Pelé7Angélique Blangy-Letheule8Pierre Miniou9Philippe Guedat10Michel De Waard11Emmanuelle Abgueguen12Bertrand Rozec13Benjamin Lauzier14Nantes Université, CHU Nantes, CNRS, INSERM, l’institut du thorax, F-44000 Nantes, FranceNantes Université, CHU Nantes, CNRS, INSERM, l’institut du thorax, F-44000 Nantes, FranceNantes Université, CHU Nantes, CNRS, INSERM, l’institut du thorax, F-44000 Nantes, FranceNantes Université, CHU Nantes, CNRS, INSERM, l’institut du thorax, F-44000 Nantes, FranceDepartment of Biochemistry, CHU de Nantes, 44800 Nantes, FranceNantes Université, CHU Nantes, CNRS, INSERM, l’institut du thorax, F-44000 Nantes, FranceNantes Université, CHU Nantes, CNRS, INSERM, l’institut du thorax, F-44000 Nantes, FranceNantes Université, CHU Nantes, CNRS, INSERM, l’institut du thorax, F-44000 Nantes, FranceNantes Université, CHU Nantes, CNRS, INSERM, l’institut du thorax, F-44000 Nantes, FranceInFlectis BioScience, 44200 Nantes, FranceInFlectis BioScience, 44200 Nantes, FranceNantes Université, CHU Nantes, CNRS, INSERM, l’institut du thorax, F-44000 Nantes, FranceInFlectis BioScience, 44200 Nantes, FranceNantes Université, CHU Nantes, CNRS, INSERM, l’institut du thorax, F-44000 Nantes, FranceNantes Université, CHU Nantes, CNRS, INSERM, l’institut du thorax, F-44000 Nantes, FranceIn clinical practice, extracorporeal circulation (ECC) is associated with coagulopathy and inflammation, eventually leading to organ injuries without preventive systemic pharmacological treatment. Relevant models are needed to reproduce the pathophysiology observed in humans and preclinical tests. Rodent models are less expensive than large models but require adaptations and validated comparisons to clinics. This study aimed to develop a rat ECC model and to establish its clinical relevance. One hour of veno-arterial ECC or a sham procedure were achieved on mechanically ventilated rats after cannulations with a mean arterial pressure objective > 60 mmHg. Five hours post-surgery, the rats’ behavior, plasmatic/blood biomarkers, and hemodynamics were measured. Blood biomarkers and transcriptomic changes were compared in 41 patients undergoing on-pump cardiac surgery. Five hours post-ECC, the rats presented hypotension, hyperlactatemia, and behavioral alterations. The same patterns of marker measurements (Lactate dehydrogenase, Creatinine kinase, ASAT, ALAT, and Troponin T) were observed in both rats and human patients. Transcriptome analyses showed similarity in both humans and rats in the biological processes involved in the ECC response. This new ECC rat model seems to resemble both ECC clinical procedures and the associated pathophysiology, but with early organ injury corresponding to a severe phenotype. Although the mechanisms at stake in the post-ECC pathophysiology of rats or humans need to be described, this new rat model appears to be a relevant and costless preclinical model of human ECC.https://www.mdpi.com/1422-0067/24/8/7338extracorporeal circulationrat modelcardiac surgerypatients cohorttranscriptomics |
| spellingShingle | Antoine Persello Fouzia Souab Thomas Dupas Virginie Aillerie Edith Bigot Manon Denis Angélique Erraud Thomas Pelé Angélique Blangy-Letheule Pierre Miniou Philippe Guedat Michel De Waard Emmanuelle Abgueguen Bertrand Rozec Benjamin Lauzier A Rat Model of Clinically Relevant Extracorporeal Circulation Develops Early Organ Dysfunctions International Journal of Molecular Sciences extracorporeal circulation rat model cardiac surgery patients cohort transcriptomics |
| title | A Rat Model of Clinically Relevant Extracorporeal Circulation Develops Early Organ Dysfunctions |
| title_full | A Rat Model of Clinically Relevant Extracorporeal Circulation Develops Early Organ Dysfunctions |
| title_fullStr | A Rat Model of Clinically Relevant Extracorporeal Circulation Develops Early Organ Dysfunctions |
| title_full_unstemmed | A Rat Model of Clinically Relevant Extracorporeal Circulation Develops Early Organ Dysfunctions |
| title_short | A Rat Model of Clinically Relevant Extracorporeal Circulation Develops Early Organ Dysfunctions |
| title_sort | rat model of clinically relevant extracorporeal circulation develops early organ dysfunctions |
| topic | extracorporeal circulation rat model cardiac surgery patients cohort transcriptomics |
| url | https://www.mdpi.com/1422-0067/24/8/7338 |
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