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Franco Valenza
Department of Pathophysiology and Transplantation
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
Lung procurement: EVLP
No conflict of interest
Lung procurement: EVLP
Evaluation, Reconditioning, Lung Repair, DCD
The donation network
EVLP pre-conditioning
Lung procurement: EVLP
Recipient
Cause of death
History
Functional
Microbiology
Diagnosis
Functional status
Procedure
Clinical, Instrumental
Visual inspection
Biopsy
Organ
Multi-organ donor
Ideal
Extended criteria
Unacceptable
… to safely increase the number of organs
Recipient
Cause of death
History
Functional
Microbiology
Diagnosis
Functional status
Procedure
Clinical, Instrumental
Visual inspection
Biopsy
Organ
Multi-organ donor
Donor treatment
Singbarlt, Am J Transpl (2011); 11:1517
Recipient
Cause of death
History
Functional
Microbiology
Diagnosis
Functional status
Procedure
Clinical, Instrumental
Visual inspection
Biopsy
Organ
Multi-organ donor
Donor treatment
Recipient
Cause of death
History
Functional
Microbiology
Diagnosis
Functional status
Procedure
Clinical, Instrumental
Visual inspection
Biopsy
Organ
Multi-organ donorEx-Vivo Lung Perfusion
Ingemansson, Ann Thor Surgl(2009);87:255
Cypel, NEJM (2011);364:1431
Van Raemdonk, Transpl Int. 2014 Mar 15. doi:10.1111/tri.12317
PaO2/FiO2 158 mmHg
Lung “Evaluation”
Lung “Reconditioning”
PaO2/FiO2 180 mmHg
PaO2/FiO2 180 mmHg
Porro, Transpl Proc (2012); 44:1830
123 89103
20
27
9
Autonomic
Brain Storm
Diagnosis of Brain
Death
Procurement
12
9
OR
ICU
Valenza, Transpl International (2014)
Valenza, Transpl International (2014)
Valenza, Transpl International (2014)
Extended criteria
EVLP
Lungs available for
transplantation
Non guidelines recipients
Is EVLP challenging the dogma?
Ischemia Reperfusion
EVLP
Preservation
Baseline
Valenza, Transpl International (2014)
Ischemia Reperfusion
EVLP
Thrombi, mediators
Preservation
Baseline
Ischemia Reperfusion
EVLP
Thrombi, mediators
Ischemia reperfusion injury
Preservation
Treatments (genes, drugs)
Baseline
Cypel, J Heart Lung Transplant (2008);27:1319
Eaton, Annu Rev Physiol (2009);71:403
PAPm(mmHg)
0
5
10
15
20
25
30
REC 0 REC 60 REC 240
0 1 2 3 4
*
*
*
Control
Beta-agonist
Valenza, J Heart Lung Transpl (2012); 31:524
Beta agonist reconditioning of donor lungs
Extended criteria
LUNG EDEMA
EVLP
Lungs available for
transplantation
Lung “Reconditioning”
Extended criteria
LUNG EDEMA
EVLP
Lungs available for
transplantation
Lung “Reconditioning”
Unacceptable
Lung “Repair”
SECRETIONS
INHALATION
Prospective observational investigation
123 subjects, 15 ICU
Time
Brain death Cold storage
REPERFUSION
Lung transplantation
AB-INGESTIS
Donor
treatment
EVLP
treatment
Valenza, Intensive Care Med exp (2014)
Valenza, Organs Tissue & Cells (2012)
Extended criteria
LUNG EDEMA
EVLP
Lungs available for
transplantation
Extended criteria
AB-INGESTIS
SECRETIONS
Donors
Cardiac Death
Accertamento di morte
Cardiaca Encefalica
20 min. ECG COLLEGIO MEDICO
PERIODO DI OSSERVAZIONE
PATOGENESI CERTA
ASSENZA FATTORI CONFONDENTI
REQUISITI CLINICO-STRUMENTALI
Assenza stato di vigilanza e coscienza
Assenza riflessi tronco encefalico
Assenza respiro spontaneo
Assenza attività elettrica cerebrale
(Assenza di flusso ematico encefalico)
ACCERTAMENTO DI MORTE
“standard neurologico”
ACCERTAMENTO DI MORTE
“standard cardiocircolatorio”
ClinicalTrials.gov: NCT02061462
Percorso “DCD-donor”
ACC sul territorio
Trasferimento in PS
Diagnosi di morte
Percorso di donazione “polmone”
Strategia di preservazione nel corpo senza vita
Valutazione qualità organo – ricondizionamento
“Ex-vivo Lung Perfusion - EVLP”
Strategia di preservazione nel corpo senza vita
semplice
esportabile
a basso costo
Percorso “DCD-donor”
... It is feasible!
12 Potenziali DCD / anno
AREU-118
Milano, Monza-Brianza (aprile-giugno 2014)
1113 Arresto Cardiocircolatorio
783 Trattamento Arresto
234 Trasferimento in Pronto soccorso
30 Età, HIV-HCV, neoplasia
…. sopravvivenza 50%
…. rate idoneità EVLP 20%
??????
12 Potenziali DCD / anno
Milano
12 Potenziali DCD / anno
Vleeshaueer, JHLT (2011);30:975
Evaluation, Reconditioning, Lung Repair, DCD
The donation network
EVLP pre-conditioning
Lung procurement: EVLP
Recipient
Organ
Multi-organ donor
Anesthestist
Perfusionist
Surgeon
Nurse
2 Students
2 Surgeons
Anesthestist
2 Nurses
Know how
Clinical- preclinical
EVLP team
Procurement team
Padova
Bergamo
Milano
Pavia
Evaluation, Reconditioning, Lung Repair, DCD
The donation network
EVLP pre-conditioning
Lung procurement: EVLP
Cypel, NEJM (2011);364:1431
Isolated perfused
Isolated perfused rat lung model (EVLP)
Inflammation
Resolution of inflammation
Heat Shock Protein
Survival / Apoptosis
Ischemic preconditioning
Early Immediate gene
Gene regulation
NFKβ
IKBα
I/R
Cytokines
Antigens
Inflammation
Resolution of inflammation
Heat Shock Protein
Survival / Apoptosis
Early Immediate gene
Ischemic preconditioning
Relativeexpression
0
2
4
6
8
10
12
Native
Ischemia
EVLP
Socs3
Socs3/Actin
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
Socs3
Actin
Gene regulation
NFKβ
IKBα
STAT3
Apoptosis
SOCS3
IPC
I/R
I/R
IL6-IL10
IL1-TNFα
Inflammation
Resolution of inflammation
Heat Shock Protein
Survival / Apoptosis
Early Immediate gene
Ischemic preconditioning
Elastase
Mieloperoxidase
Catalase
pz in lista d'attesa trapianti effettuati
numero
0
20
40
60
80
100
120
Waitlist Lung Tx
death
… in conclusion
pz in lista d'attesa trapianti effettuati
numero
0
20
40
60
80
100
120
decessi
Donor
DCD
EVLP
Waitlist Lung Tx
death
… in conclusion
Lung Transplant MI-Policlinico
Year
2005 2006 2007 2008 2009 2010 2011 2012
N°ofLungTransplant
0
5
10
15
20
25 EVLP
ECMO bridge to transplant
Standard Recipient
EVLP project
2013 2014
U.O. Anestesia e Rianimazione
U.O. Chirurgia Generale ad Orientamento Toracico
Infermieri Camera Opreatoria Zonda
Centro di Ricerche Chirurgiche Precliniche
Direzione Scientifica , Generale
Fondazione Ca’ Granda
Sponsors of the project
Regione Lombardia
Centro Nazionale Trapianti
Lega Lombarda Fibrosi Cistica
Uknowledgments
Silvia, Sara, Jacopo, Alessandro, Giulia, Grazia, Stefano,
Katia, Patrizia, Andrea, Daniele…
Research Team
… to you for your attention!
Uknowledgments
La mia esperienza innovativa è... la perfusione degli organi

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