Background: In lung transplantation (LuTx), various ischemic phases exist, yet the rewarming ischemia time (RIT) during implantation has often been overlooked. During RIT, lungs are deflated and exposed to the body temperature in the recipient's chest cavity. Our prior clinical findings demonstrated that prolonged RIT increases the risk of primary graft dysfunction. However, the molecular mechanisms of rewarming ischemic injury in this context remain unexplored. We aimed to characterize the rewarming ischemia phase during LuTx by measuring organ temperature and comparing transcriptome and metabolome profiles in tissue obtained at the end versus the start of implantation.
Methods: In a clinical observational study, 34 double-LuTx with ice preservation were analyzed. Lung core and surface temperature (n = 65 and 55 lungs) were measured during implantation. Biopsies (n = 59 lungs) were wedged from right middle lobe and left lingula at start and end of implantation. Tissue transcriptomic and metabolomic profiling were performed.
Results: Temperature increased rapidly during implantation, reaching core/surface temperatures of 21.5°C/25.4°C within 30 minutes. Transcriptomics showed increased proinflammatory signaling and oxidative stress at the end of implantation. Upregulation of NLRP3 and NFKB1 correlated with RIT. Metabolomics indicated elevated levels of amino acids, hypoxanthine, uric acid, and cysteineglutathione disulfide alongside decreased levels of glucose and carnitines. Arginine, tyrosine, and 1-carboxyethylleucine showed a correlation with incremental RIT.
Conclusions: The final rewarming ischemia phase in LuTx involves rapid organ rewarming, accompanied by transcriptomic and metabolomic changes indicating proinflammatory signaling and disturbed cell metabolism. Limiting implantation time and cooling of the lung represent potential interventions to alleviate rewarming ischemic injury.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.healun.2024.10.020 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dynamic Preservation of Donation After Circulatory Death Liver Grafts From Donors Aged 60 y and Older.
Transplantation
December 2024
Laboratory of Abdominal Transplantation, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
Background: Donor livers from older donation after circulatory death (DCD) donors are frequently discarded for transplantation because of the high risk of graft failure. It is unknown whether DCD livers from older donors benefit from dynamic preservation.
Methods: In a multicenter study, we retrospectively compared graft and patient outcomes after transplantation of livers from DCD donors older than 60 y, preserved with either static cold storage (SCS), ex situ sequential dual hypothermic perfusion, controlled oxygenated rewarming, and normothermic perfusion (DHOPE-COR-NMP), or in situ abdominal normothermic regional perfusion (aNRP).
Lack of additional benefit from slow rewarming after therapeutic hypothermia for ischaemic brain injury in near-term fetal sheep.
J Physiol
December 2024
Department of Physiology, the University of Auckland, Auckland, New Zealand.
The optimal rate of rewarming after therapeutic hypothermia is unclear. Slow rewarming may reduce cardiovascular instability and rebound seizures, but there is little controlled evidence to support this. The present study aimed to determine whether slow rewarming can improve neuroprotection after 72 h of hypothermia.
View Article and Find Full Text PDFThe effect of rewarming ischemia on tissue transcriptome and metabolome signatures: A clinical observational study in lung transplantation.
J Heart Lung Transplant
October 2024
Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium; Department of Chronic Diseases and Metabolism, Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, Leuven, Belgium. Electronic address:
Background: In lung transplantation (LuTx), various ischemic phases exist, yet the rewarming ischemia time (RIT) during implantation has often been overlooked. During RIT, lungs are deflated and exposed to the body temperature in the recipient's chest cavity. Our prior clinical findings demonstrated that prolonged RIT increases the risk of primary graft dysfunction.
View Article and Find Full Text PDFAdjuvant High-Dose Erythropoietin With Delayed Therapeutic Hypothermia in Neonatal Hypoxic-Ischemic Encephalopathy.
Pediatr Neurol
December 2024
Faculty of Medicine, Division of Neurology, Department of Pediatrics, Chiang Mai University, Chiang Mai, Thailand. Electronic address:
Background: To evaluate the benefits of high-dose erythropoietin (EPO) combined with therapeutic hypothermia (TH) on brain magnetic resonance imaging (MRI) scores and neurodevelopmental outcomes in neonates with moderate to severe hypoxic-ischemic-ecephalopathy (HIE), especially in neonates who received TH between six to 12 hours of birth.
Methods: This prospective, single-blind, randomized, placebo-controlled trial enrolled term newborns with moderate to severe HIE admitted to neonatal intensive care unit between April 2018 and April 2022. Hypothermia was started within 12 hours of birth.
Changes in Neonatal Intraoperative Electroencephalogram Alpha: Delta Ratios Precede Neurologic Injury.
World J Pediatr Congenit Heart Surg
January 2025
Department of Internal Medicine-Pediatrics, University of Rochester Medical Center, Rochester, NY, USA.
Unrecognized intraoperative cerebral ischemia during neonatal aortic arch reconstruction may precede neurologic injury. Electroencephalogram (EEG) alpha:delta ratio (A:D) changes predict cerebral ischemia; however, if A:D differences can identify ischemia during neonatal antegrade cerebral perfusion (ACP) and aortic arch reconstruction is unknown. We hypothesized that A:D changes would precede neurologic injury.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!