TY - JOUR
T1 - Regulated hepatic reperfusion mitigates ischemia-reperfusion injury and improves survival after prolonged liver warm ischemia
T2 - A pilot study on a novel concept of organ resuscitation in a large animal model
AU - Hong, Johnny C.
AU - Koroleff, Dimitri
AU - Xia, Victor
AU - Chang, Chun Ming
AU - Duarte, Sergio M.
AU - Xu, Junming
AU - Lassman, Charles
AU - Kupiec-Weglinski, Jerzy
AU - Coito, Ana J.
AU - Busuttil, Ronald W.
N1 - Funding Information:
This work was supported in part by the American Association for the Study of Liver Diseases (AASLD) grant to Johnny C Hong, MD, FACS, recipient of the 2009 AASLD Career Development Award in Liver Transplantation. The authors gratefully acknowledge Larry Barcliff, RRT, Grace Chang, MD, Tyrone Wong, Ming Ye, MD, and Richard Graul, PharmD, PhD, for their technical assistance in the laboratory. We also acknowledge Gerald D Buckberg, MD, for his pioneering work in the development of controlled reperfusion and cardioplegia for cardiac surgery.
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jamcollsurg.2011.12.010
DO - 10.1016/j.jamcollsurg.2011.12.010
M3 - Article
C2 - 22321520
AN - SCOPUS:84862831136
SN - 1072-7515
VL - 214
SP - 505
EP - 515
JO - Journal of the American College of Surgeons
JF - Journal of the American College of Surgeons
IS - 4
ER -