studies

320A AASLD ABSTRACTS HEPATOLOGY, October, 2015
215
The transportable machine perfusion Airdrive®, a novel
approach to safely expand the donor pool for liver
transplantation
Philippe Compagnon 1,2 , Ismail Ben Mosbah 2 , Hassen Hentati 1 ,
Eric Levesque 3 , Mara Disabato 1 , Jose L. Cohen 2 , Daniel Azoulay 1 ;
1 Service de Chirurgie Digestive et Hépatobiliaire -Transplantation
Hépatique, Hopital Henri Mondor - Assistance Publique-Hopitaux
de Paris, Université Paris-Est, Creteil, France; 2 IMRB- Inserm U955,
Hopital Henri Mondor, Assistance Publique-Hopitaux de Paris, Université
Paris-Est créteil, Créteil, France; 3 Service de Réanimation
Digestive, Hopital Henri Mondor, Assitance Publique-Hopitaux de
Paris, Université Paris-Est, Créteil, France
Background and Aims: Livers derived from donation after
circulatory death (DCD) suffer warm ischemia (WI) and are
infrequently used for transplantation; they have the potential,
however, to considerably expand the donor pool. The
Airdrive® is the first transportable oxygenated machine perfusion
(MP) unit suitable for liver preservation. We aimed
to determine whether the Airdrive® MP would improve the
quality of these livers using a DCD large animal model. Methods:
Female large white pigs were used as organ donors and
recipients. Liver allografts procured from heart beating donors
and preserved by simple cold storage (SCS) served as controls
(n=6). In experimental groups, cardiac arrest was induced by
IV injection of KCL. After 60min WI, livers were perfused in
situ with HTK and subsequently preserved either by SCS (SCS
group, n=3) or hypothermic MP (Airdrive® group, n=4) using
MPS-Belzer solution. After 4hr of preservation, all livers were
transplanted into recipient pigs. The main judgment criterion
was animal survival at day 5 Results: All animals that received
a simple cold stored liver allograft after 60min WI experienced
PNF and died within 6 hours after transplantation (5-day survival
= 0%). In contrast, 5-day survival in animals that received
a MP liver was 100% (4/4, Airdrive® group) as well as in
controls (6/6). A post-reperfusion syndrome was observed in
all animals (3/3) of the SCS group but none of the control
or Airdrive® groups. These phenomena caused a significant
increase in fluid challenge and catecholamine needs in SCS
group relative to control and Airdrive® groups. At the end of
cold preservation, ATP content was significantly higher in the
Airdrive® group vs. SCS group. After reperfusion, MP livers
functioned better (albumin production, prothrombin time rates)
and showed less hepatocellular and endothelial cell injury, in
agreement with better preserved liver integrity (histology) vs.
SCS group. MP livers also exhibited higher ATP recovery than
SCS livers. The protective effect of the Airdrive® device was
associated with a significant attenuation of oxidative stress
(lower lipid peroxidation, higher catalase and superoxide
dismutase activity), and a better endoplasmic reticulum adaptation
leading to limit mitochondrial damage (cytochrome c,
caspase 9, GLDH), and apoptosis (caspase 3 and TUNEL) Conclusions:
This study demonstrates for the first time the efficacy of
the transportable MP Airdrive® device to enhance donor liver
viability for transplantation in a clinically relevant DCD model.
Disclosures:
The following authors have nothing to disclose: Philippe Compagnon, Ismail Ben
Mosbah, Hassen Hentati, Eric Levesque, Mara Disabato, Jose L. Cohen, Daniel
Azoulay
216
A Novel Percutaneous Organ Perfusion Stent Improves
Liver Perfusion in a Porcine Model of Donation after
Cardiac Death
Bryan Tillman 1 , Youngjae Chun 2 , Nathan L. Liang 1 , Tara D. Richards
1 , Anthony J. Demetris 4 , Timothy M. Maul 2 , Amit D. Tevar 3 ;
1 Division of Vascular Surgery, University of Pittsburgh Medical
Center, Pittsburgh, PA; 2 Swanson School of Engineering, University
of Pittsburgh, Pittsburgh, PA; 3 Starzl Transplant Institute, University
of Pittsburgh Medical Center, Pittsburgh, PA; 4 Department of
Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA
Introduction: Donation after cardiac death (DCD) liver allografts
are frequently discarded due to ischemia during the agonal
period prior to cardiac death. A dual-chambered Organ Perfusion
Stent (OPS) would isolate blood flow to the abdominal
organs to maintain perfusion, while agonal cardiac flow would
pass through a large central lumen. As a result, this approach
would isolate perfusion to the liver from the unstable circulation
of the agonal donor without affecting donor cardiac
death. Methods: OPS were constructed with a central lumen
for cardiac flow and an external visceral perfusion chamber. A
porcine model included three control and six stent animals. The
OPS was deployed through endovascular sheaths in the aorta
to include the visceral branches while under cardiac monitoring.
Venous blood from a separate cannula was cycled through
an oxygenator and back to the isolated visceral arteries. Next,
the DCD agonal period was simulated for 60 minutes with a
target MAP of 40 mm Hg. Results: Angiography of the outer
chamber confirmed perfusion of the visceral organs, while
agonal cardiac blood flow passed through the central lumen.
During stent placement, no change was observed in cardiac
parameters of HR, RVEDV, CVP, MAP, or SvO2 (P > 0.05)
(n=6). Cardiac output decreased by an average 11% consistent
with offloading of visceral perfusion (P=0.01). Stented
animals revealed an average of 4.8 fold improved oxygen
delivery compared to controls. Following the agonal period,
the livers of the controls revealed marked ischemic appearance
contrasting to the adequately perfused livers of the stent treated
animals. Conclusions: This novel OPS achieves improved oxygen
delivery to visceral organs without significantly impacting
cardiac physiology of the donor. A single deployment step
allows for collective isolation of all four visceral branches. In
summary, this novel approach may significantly increase the
quality of livers available for transplantation.
Disclosures:
Timothy M. Maul - Advisory Committees or Review Panels: Mallinckrodt
The following authors have nothing to disclose: Bryan Tillman, Youngjae Chun,
Nathan L. Liang, Tara D. Richards, Anthony J. Demetris, Amit D. Tevar