Evidence map›Paper›PMID 29289364›Full record

ArticleThe Annals of thoracic surgery2018

Imatinib Is Protective Against Ischemia-Reperfusion Injury in an Ex Vivo Rabbit Model of Lung Injury.

J Trent Magruder, Joshua C Grimm, Todd C Crawford, Laura Johnston, Lakshmi Santhanam, R Scott Stephens, Dan E Berkowitz, Ashish S Shah, Errol L Bush, Mahendra Damarla and 3 more

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Article in The Annals of thoracic surgery, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Ex-vivo lung perfusion therapies: do they add value to organ donation?Current opinion in organ transplantation · 2022
    Review
  5. Review
  6. Article
  7. Repurposing anticancer drugs for the management of COVID-19.European journal of cancer (Oxford, England : 1990) · 2020
    Review
  8. Article
  9. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

J Trent MagruderDivision of Cardiac Surgery, Department of Surgery, Johns Hopkins University, Baltimore, Maryland.
Joshua C GrimmDivision of Cardiac Surgery, Department of Surgery, Johns Hopkins University, Baltimore, Maryland.
Todd C CrawfordDivision of Cardiac Surgery, Department of Surgery, Johns Hopkins University, Baltimore, Maryland.
Laura JohnstonDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
Lakshmi SanthanamDepartment of Anesthesia and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland.
R Scott StephensDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
Dan E BerkowitzDepartment of Cardiac Surgery, Vanderbilt University, Nashville, Tennessee.
Ashish S ShahDepartment of Cardiac Surgery, Vanderbilt University, Nashville, Tennessee.
Errol L BushDivision of Thoracic Surgery, Department of Surgery, Johns Hopkins University, Baltimore, Maryland.
Mahendra DamarlaDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
Rachel L DamicoDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
Paul M HassounDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
Bo S KimDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, Maryland. Electronic address: bkim38@jhmi.edu.

Funding

Targeting Divergent Roles of Caspase 3 to Promote Endothelial Barrier IntegrityR01HL133413 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI DAMARLA, MAHENDRA · 2016 to 2020
$2.0M
MAP Kinase Signaling in Apoptosis-Induced Ventilator-Associated Lung InjuryK08HL097024 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI DAMARLA, MAHENDRA · 2009 to 2013
$805k
NHLBI NIH HHS K08 HL097024
6 · The paper itself

Abstract

backgroundIschemia-reperfusion injury is characterized by an increase in oxidative stress and leads to significant morbidity and death. The tyrosine kinase c-Abl is activated by oxidative stress and mediates processes that affect endothelial barrier function. We hypothesized treatment with the c-Abl inhibitor imatinib would be protective against ischemia-reperfusion injury in our ex vivo rabbit model.

methodsHeart-lung blocs were harvested from rabbits and stored in cold in Perfadex (Vitrolife, Englewood, CO) for 18 hours. Blocs were reperfused for 2 hours in an ex vivo circuit with donor rabbit blood alone (untreated group, n = 7) or donor rabbit blood and 4 mg imatinib (treatment group, n = 10). Serial clinical variables measured every 15 minutes (arterial oxygen and carbon dioxide tension and mean pulmonary artery pressures) and biochemistry of tissue samples before and after reperfusion were assessed.

resultsCompared with untreated lungs, imatinib treatment improved physiologic parameters, including oxygen, carbon dioxide, and pulmonary artery pressures. Imatinib-treated lungs had less vascular barrier dysfunction as quantified by wet-to-dry weight ratios and bronchoalveolar lavage protein concentrations. Treated lungs showed less inflammation as measured by bronchoalveolar lavage myeloperoxidase assay, less mitochondrial reactive oxygen species production, and increased antioxidant catalase levels. Finally, imatinib protected lungs from DNA damage and p53 upregulation.

conclusionsImatinib treatment significantly improved the physiologic performance of reperfused lungs and biochemical indicators associated with reperfusion injury in this ex vivo model. Further study is necessary to elucidate the mechanism of tyrosine kinase inhibition in lungs exposed to ischemia and reperfusion.

Indexed as

AnimalsDisease Models, AnimalImatinib MesylateLung InjuryLung TransplantationMaleProtein Kinase InhibitorsRabbitsReperfusion InjuryImatinib MesylateProtein Kinase Inhibitors

Identifiers

PMID29289364

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.