A systematic review of pharmacological treatment options used to reduce ischemia reperfusion injury in rat liver transplantation.
BACKGROUND
Although animal studies models are frequently used for the purpose of attenuating ischemia reperfusion injury (IRI) in liver transplantation (LT), many of pharmacological agents have not become part of clinical routine.


METHODS
A search was performed using the PubMed database to identify agents, from which 58 articles containing 2700 rat LT procedures were selected. The identified pharmacological agents were categorized as follows: I - adenosine agonists, nitric oxide agonists, endothelin antagonists, and prostaglandins, II - Kupffer cell inactivator, III - complement inhibiter, IV - antioxidant, V - neutrophil inactivator, VI -anti-apoptosis agent, VII - heat shock protein and nuclear factor kappa B inducer, VIII - metabolic agent, IX - traditional Chinese medicine, and X - others. Meta-analysis using 7-day-survival rate was also performed with Mantel-Haenszel's Random effects model.


RESULTS
The categorization revealed that the rate of donor-treated experiments in each group was highest for agents from Group II (70%) and VII (71%), whereas it was higher for agents from Group V (83%) in the recipient-treated experiments. Furthermore, 90% of the experiments with agents in Group II provided 7-day-survival benefits. The Risk Ratio (RR) of the meta-analysis was 2.43 [95% CI: 1.88-3.14] with moderate heterogeneity. However, the RR of each of the studies was too model-dependent to be used in the search for the most promising pharmacological agent.


CONCLUSIONS
With regard to hepatic IRI pathology, the categorization of agents of interest would be a first step in designing suitable multifactorial and pleiotropic approaches to develop pharmacological strategies.
Department of General and Transplant Surgery, University Hospital of Heidelberg, Heidelberg, Germany; Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Kenya
K
Yamanaka
Department of General and Transplant Surgery, University Hospital of Heidelberg, Heidelberg, Germany.
Philipp
P
Houben
Department of General and Transplant Surgery, University Hospital of Heidelberg, Heidelberg, Germany.
Helge
H
Bruns
Department of General and Transplant Surgery, University Hospital of Heidelberg, Heidelberg, Germany.
Daniel
D
Schultze
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Etsuro
E
Hatano
Department of General and Transplant Surgery, University Hospital of Heidelberg, Heidelberg, Germany.
Peter
P
Schemmer
D000818:Animals; D004195:Disease Models, Animal; D004358:Drug Therapy / Q000379:methods*; D016031:Liver Transplantation / Q000009:adverse effects*; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D015996:Survival Rate; D016896:Treatment Outcome