Regulated hepatic reperfusion mitigates ischemia-reperfusion injury and improves survival after prolonged liver warm ischemia: a pilot study on a novel concept of organ resuscitation in a large animal model.
BACKGROUND
Ischemia-reperfusion injury (IRI) can occur during hepatic surgery and transplantation. IRI causes hepatic mitochondrial and microcirculatory impairment, resulting in acute liver dysfunction and failure. We proposed a novel strategy of regulated hepatic reperfusion (RHR) to reverse the cellular metabolic deficit that incurred during organ ischemia by using a substrate-enriched, oxygen-saturated, and leukocyte-depleted perfusate delivered under regulated reperfusion pressure, temperature, and pH. We investigate the use of RHR in mitigating IRI after a prolonged period of warm ischemia.


METHODS
Using a 2-hour liver warm ischemia swine model, 2 methods of liver reperfusion were compared. The control group (n = 6) received conventional reperfusion with unmodified portal venous blood under unregulated reperfusion pressure, temperature, and pH. The experimental group (n = 6) received RHR. We analyzed the effects of RHR on post-reperfusion hemodynamic changes, liver function, and 7-day animal survival.


RESULTS
RHR resulted in 100% survival compared with 50% in the control group (p = 0.05). Post-reperfusion syndrome was not observed in the RHR group, but it occurred in 83% of the control group. RHR resulted in a lesser degree of change from baseline serum alanine aminotransferase levels, aspartate aminotransferase, and lactate dehydrogenase after reperfusion compared with the control group. Histopathologic evaluation showed minimal ischemic changes in the RHR group, whereas a considerable degree of coagulative hepatocellular necrosis was observed in the control group.


CONCLUSIONS
Regulated hepatic reperfusion mitigates IRI, facilitates liver function recovery, and improves survival after a prolonged period of hepatic warm ischemia. This novel strategy has potential applicability to clinical hepatic surgery and liver transplantation when marginal grafts are used.
Dumont-UCLA Transplant and Liver Cancer Center, Pfleger Liver Institute, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA 90095-7054, USA. johnnyhong@mednet.ucla.edu
Johnny C
JC
Hong
Dimitri
D
Koroleff
Victor
V
Xia
Chun Ming
CM
Chang
Sergio M
SM
Duarte
Junming
J
Xu
Charles
C
Lassman
Jerzy
J
Kupiec-Weglinski
Ana J
AJ
Coito
Ronald W
RW
Busuttil
D000818:Animals; D004195:Disease Models, Animal; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000473:pathology / Q000502:physiology / Q000601:surgery*; D008111:Liver Function Tests; D016031:Liver Transplantation; D010865:Pilot Projects; D015424:Reperfusion / Q000009:adverse effects / Q000379:methods*; D015427:Reperfusion Injury / Q000517:prevention & control*; D012151:Resuscitation; D015996:Survival Rate; D013552:Swine; D013997:Time Factors; D052096:Warm Ischemia / Q000401:mortality