Components, Doses, Mechanisms, and Relevant Experimental and Clinical Evidence of the Combined Drug Approach
thrombosis, death, TNF-α, tumor necrosis, toxicity, inflammation, kidney reperfusion injury, parenchymal injury, congestion, myocardial injury, ischemia reperfusion, hepatocellular injury
THROMBOSIS, PRINGLE, TUMOR NECROSIS, INFLAMMATION, ACUTE KIDNEY FAILURE, LIVER REGENERATION, CONGESTION, ADHESION, HEPATOCELLULAR INJURY
 Improvement of IRI severity, elimination of primary nonfunction, reduction of inflammatory cytokines such as TNF-α, improvement in liver function, reduction of bile salt toxicity, and increase of survival in a stringent pig DCD model of LT Improvement of hepatocellular injury, lipid peroxidation, and function in rat liver in situ reperfusion model Reduction of AST levels and ICU LOS after human partial liver resection Prevention of inflammation and parenchymal injury in isolated rat liver perfusion model Included in proof of concept; improvement in IRI severity, elimination of primary nonfunction, reduction of inflammatory cytokines such as TNF-α, improvement in liver function, reduction of bile salt toxicity, and increase in survival in a stringent pig DCD model of LT Improvement of hepatocellular injury and survival rate in pig liver in situ reperfusion model Decrease of serum aminotransferase and lactate and sinusoidal congestion in pig LT model Improvement of hepatocellular injury Improvement in creatinine values, malondialdehyde levels, myeloperoxidase activity, and histological damage in rat kidney in situ reperfusion model Reduction of neutrophil rolling and adhesion in a feline mesentery in situ reperfusion model Increase in the release of prostacyclin, improvement of blood flow, and decrease of cytokine-induced neutrophil chemoattractant and myeloperoxidase in rat liver in situ reperfusion model Reduction of graft thrombosis incidence in human simultaneous pancreas kidney transplant Prolonging of long-term survival after human intestinal transplant when used as a component of an immunomodulatory strategy Improvement of hepatocellular injury and decrease of myeloperoxidase in rat liver in situ reperfusion model Improvement of hepatocellular injury, apoptosis, and survival in mice liver in situ reperfusion model Included in proof of concept; improvement of IRI severity, elimination of primary nonfunction, reduction of inflammatory cytokines such as TNF-α, improvement of liver function, reduction of bile salt toxicity, and increase in survival in a stringent pig DCD model of LT Improvement of kidney reperfusion injury and acute kidney failure, decrease of complement activation and ROS formation in mice in situ reperfusion model Improvement of hepatocellular injury and apoptosis in pig liver in situ reperfusion model Reduction of inflammatory cytokine (IL-6 and TNF-α) and hospital LOS after human partial liver resection and Pringle maneuver Improvement of hepatocellular injury and function in rat liver in situ reperfusion model Improvement of hepatocellular injury and decrease of inflammatory cell infiltration and histological damage in pig liver ex situ reperfusion model Improvement of hepatocellular injury, liver regeneration, and survival in mice liver in situ reperfusion model Improvement of myocardial injury, hemodynamic parameters, and hospital LOS in human coronary artery bypass graftingAbbreviations: AST, aspartate aminotransferase; DCD, donation after circulatory death; EPO-β, recombinant erythropoietin-β; ICU, intensive care unit; IL-6, interleukin 6; IRI, ischemia reperfusion injury; LOS, length of stay; LT, liver transplant; ROS, reactive oxygen species; TNF-α, tumor necrosis factor α.