Abstract
Background Ischemic preconditioning (IPC), either direct (DIPC) or remote (RIPC), is a procedure aimed at reducing the harmful effects of ischemia-reperfusion (I/R) injury. Objectives To assess the local and systemic effects of DIPC, RIPC, and both combined, in the pig liver transplant model. Materials and methods Twenty-four pigs underwent orthotopic liver transplantation and were divided into 4 groups: control, direct donor preconditioning, indirect preconditioning at the recipient, and direct donor with indirect recipient preconditioning. The recorded parameters were: donor and recipient weight, graft-to-recipient weight ratio (GRWR), surgery time, warm and cold ischemia time, and intraoperative hemodynamic values. Blood samples were collected before native liver removal (BL) and at 0 h, 1 h, 3 h, 6 h, 12 h, 18 h, and 24 h post-reperfusion for the biochemical tests: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), creatinine, BUN (blood urea nitrogen), lactate, total and direct bilirubin. Histopathological examination of liver, gut, kidney, and lung fragments were performed, as well as molecular analyses for expression of the apoptosis-related BAX (pro-apoptotic) and Bcl-XL (anti-apoptotic) genes, eNOS (endothelial nitric oxide synthase) gene, and IL-6 gene related to inflammatory ischemia-reperfusion injury, using real-time polymerase chain reaction (RT-PCR). Results There were no differences between the groups regarding biochemical and histopathological parameters. We found a reduced ratio between the expression of the BAX gene and Bcl-XL in the livers of animals with IPC versus the control group. Conclusions DIPC, RIPC or a combination of both, produce beneficial effects at the molecular level without biochemical or histological changes.
Highlights
Ischemic preconditioning (IPC), either direct (DIPC) or remote (RIPC), is a procedure aimed at reducing the harmful effects of ischemia-reperfusion injury
We found a reduced ratio between the expression of the pro-apoptotic BAX gene and the expression of the anti-apoptotic Bcl gene in the livers of animals with IPC versus the control group
In remote ischemic preconditioning (RIPC), the procedure is applied to another organ, with the protective effect on the target organ being exerted by biochemical mediators activated at a distance and carried by the blood stream, without direct stress or trauma to the organ.[6]
Summary
Ischemic preconditioning (IPC), either direct (DIPC) or remote (RIPC), is a procedure aimed at reducing the harmful effects of ischemia-reperfusion injury. Direct ischemic preconditioning (DIPC) has the disadvantage of causing mechanical stress to the main vascular structures of the organ.[5] In remote ischemic preconditioning (RIPC), the procedure is applied to another organ, with the protective effect on the target organ being exerted by biochemical mediators activated at a distance and carried by the blood stream, without direct stress or trauma to the organ.[6] The effect of RIPC was first demonstrated on the myocardium of rats submitted to renal IPC.[5] So far, there is no consensus about the best method of RIPC, i.e., the number of I/R cycles, the effective I/R time required to trigger the protective stimulus, and the choice of the I/R site to maximize the beneficial effects of IPC with the least possible damage to the body Notwithstanding these unanswered questions, the short-term occlusion of the mesenteric artery has been proven of great importance, with positive effects on several organs.[5]
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