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The impact of alteplase on pulmonary graft function in donation after circulatory death - An experimental study

Liersch-Nordqvist, Annika LU ; Fakhro, Mohammed LU ; Pierre, Leif LU ; Hlebowicz, Joanna LU ; Malmsjö, Malin LU ; Ingemansson, Richard LU and Lindstedt, Sandra LU (2017) In Annals of medicine and surgery (2012) 22. p.1-6
Abstract

OBJECTIVE: Lung transplantation is hampered by the lack of organs resulting in deaths on the waiting list. The usage of donation after circulatory death (DCD) lungs would dramatically increase donor availability. The most optimal organ preservation method, and the need for antithrombotic and fibrinolytic treatment to prevent thrombosis in the donor lungs is currently on debate. The present study investigated, in a simulated clinical DCD situation, whether the addition of alteplase in the flush-perfusion solution at the time of pulmonary graft harvesting could prevent thrombosis in the donor lung and thereby improve pulmonary graft function.

METHODS: Twelve Swedish domestic pigs were randomized into two groups. All animals... (More)

OBJECTIVE: Lung transplantation is hampered by the lack of organs resulting in deaths on the waiting list. The usage of donation after circulatory death (DCD) lungs would dramatically increase donor availability. The most optimal organ preservation method, and the need for antithrombotic and fibrinolytic treatment to prevent thrombosis in the donor lungs is currently on debate. The present study investigated, in a simulated clinical DCD situation, whether the addition of alteplase in the flush-perfusion solution at the time of pulmonary graft harvesting could prevent thrombosis in the donor lung and thereby improve pulmonary graft function.

METHODS: Twelve Swedish domestic pigs were randomized into two groups. All animals underwent ventricular fibrillation and were then left untouched for 1 h after declaration of death. None of the animals received heparin. The lungs were then harvested and flush-perfused with Perfadex(®) solution and the organs were then stored at 8 °C for 4 h. In one group alteplase was added to the Perfadex(®) solution (donation after cardiac death with alteplase (DCD-A)) and in the other, it was not (DCD). Lung function was evaluated, using ex vivo lung perfusion (EVLP), with blood gases at different oxygen levels, pulmonary vascular resistance (PVR), lung weight, and macroscopic appearance.

RESULTS: During EVLP, there were no significant differences between groups in PaO2 at any investigated FiO2 level (1.0, 0.5, or 0.21). At FiO2 1.0, the PaO2 in the DCD and DCD-A was 51.7 ± 2.05 kPa and 60.3 ± 3.67 kPa, respectively (p = 0.1320). There were no significant differences between groups PVR levels, in the DCD (372 ± 31 dyne x s/cm(5)) and in the DCD-A (297 ± 37 dyne x s/cm(5)) groups (p = 0.1720). There was no significant difference between groups in macroscopic appearance.

CONCLUSIONS: All the lungs showed excellent blood gases after EVLP, and they all meet the criteria's for clinical lung transplantation. The use of alteplase did not seem to have any obvious benefit to the donor lungs in a DCD situation. The donor lungs treated with alteplas showed slightly better blood gases and slightly lower PVR compared to the group without alteplas, however the difference was not significant. DCD appears to be a safe and effective method to expand the donor pool.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Pulmonary graft, Lung transplantation, EVLP, DCD
in
Annals of medicine and surgery (2012)
volume
22
pages
6 pages
publisher
Elsevier
external identifiers
  • scopus:85027396134
  • wos:000413812000001
ISSN
2049-0801
DOI
10.1016/j.amsu.2017.08.010
language
English
LU publication?
yes
id
8e24e86f-9b65-472d-bcc5-c7bd109a5b25
date added to LUP
2017-08-29 21:09:46
date last changed
2018-01-16 13:23:53
@article{8e24e86f-9b65-472d-bcc5-c7bd109a5b25,
  abstract     = {<p>OBJECTIVE: Lung transplantation is hampered by the lack of organs resulting in deaths on the waiting list. The usage of donation after circulatory death (DCD) lungs would dramatically increase donor availability. The most optimal organ preservation method, and the need for antithrombotic and fibrinolytic treatment to prevent thrombosis in the donor lungs is currently on debate. The present study investigated, in a simulated clinical DCD situation, whether the addition of alteplase in the flush-perfusion solution at the time of pulmonary graft harvesting could prevent thrombosis in the donor lung and thereby improve pulmonary graft function.</p><p>METHODS: Twelve Swedish domestic pigs were randomized into two groups. All animals underwent ventricular fibrillation and were then left untouched for 1 h after declaration of death. None of the animals received heparin. The lungs were then harvested and flush-perfused with Perfadex(®) solution and the organs were then stored at 8 °C for 4 h. In one group alteplase was added to the Perfadex(®) solution (donation after cardiac death with alteplase (DCD-A)) and in the other, it was not (DCD). Lung function was evaluated, using ex vivo lung perfusion (EVLP), with blood gases at different oxygen levels, pulmonary vascular resistance (PVR), lung weight, and macroscopic appearance.</p><p>RESULTS: During EVLP, there were no significant differences between groups in PaO2 at any investigated FiO2 level (1.0, 0.5, or 0.21). At FiO2 1.0, the PaO2 in the DCD and DCD-A was 51.7 ± 2.05 kPa and 60.3 ± 3.67 kPa, respectively (p = 0.1320). There were no significant differences between groups PVR levels, in the DCD (372 ± 31 dyne x s/cm(5)) and in the DCD-A (297 ± 37 dyne x s/cm(5)) groups (p = 0.1720). There was no significant difference between groups in macroscopic appearance.</p><p>CONCLUSIONS: All the lungs showed excellent blood gases after EVLP, and they all meet the criteria's for clinical lung transplantation. The use of alteplase did not seem to have any obvious benefit to the donor lungs in a DCD situation. The donor lungs treated with alteplas showed slightly better blood gases and slightly lower PVR compared to the group without alteplas, however the difference was not significant. DCD appears to be a safe and effective method to expand the donor pool.</p>},
  author       = {Liersch-Nordqvist, Annika and Fakhro, Mohammed and Pierre, Leif and Hlebowicz, Joanna and Malmsjö, Malin and Ingemansson, Richard and Lindstedt, Sandra},
  issn         = {2049-0801},
  keyword      = {Pulmonary graft,Lung transplantation,EVLP,DCD},
  language     = {eng},
  pages        = {1--6},
  publisher    = {Elsevier},
  series       = {Annals of medicine and surgery (2012)},
  title        = {The impact of alteplase on pulmonary graft function in donation after circulatory death - An experimental study},
  url          = {http://dx.doi.org/10.1016/j.amsu.2017.08.010},
  volume       = {22},
  year         = {2017},
}