Hypoxic preconditioning in renal ischaemia–reperfusion injury: a review in pre-clinical models

Ischaemia–reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and chronic kidney disease, which consists of cellular damage and renal dysfunction. AKI is a major complication that is of particular concern after cardiac surgery and to a lesser degree following organ transplantation in the immediate post-transplantation period, leading to delayed graft function. Because effective therapies are still unavailable, several recent studies have explored the potential benefit of hypoxic preconditioning (HPC) on IRI. HPC refers to the acquisition of increased organ tolerance to subsequent ischaemic or severe hypoxic injury, and experimental evidences suggest a potential benefit of HPC. There are three experimental forms of HPC, and, for better clarity, we named them as follows: physical HPC, HPC via treated-cell administration and stabilised hypoxia-inducible factor (HIF)-1α HPC, or mimicked HPC. The purpose of this review is to present the latest developments in the literature on HPC in the context of renal IRI in pre-clinical models. The data we compiled suggest that preconditional activation of hypoxia pathways protects against renal IRI, suggesting that HPC could be used in the treatment of renal IRI in transplantation.

Effect of sleeve gastrectomy, Roux-en-Y gastric bypass, and ileal transposition on myocardial ischaemia–reperfusion injury in non-obese non-diabetic rats

Bariatric surgery (BS) improves outcomes in patients with myocardial infarction (MI). Here we tested the hypothesis that BS-mediated reduction in fatal MI could be attributed to its infarct-limiting effect. Wistar rats were randomized into five groups: control (CON), sham (SHAM), Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and ileotransposition (IT). Ten weeks later, animals were subjected to 30-min myocardial ischemia plus 120-min reperfusion. Infarct size (IS) and no-reflow area were determined histochemically. Fasting plasma levels of glucagon-like peptide-1 (GLP-1), leptin, ghrelin, and insulin were measured using ELISA. Compared with SHAM, RYGB and SG reduced IS by 22% (p = 0.011) and 10% (p = 0.027), and no-reflow by 38% (p = 0.01) and 32% (p = 0.004), respectively. IT failed to reduce IS and no-reflow. GLP-1 level was increased in the SG and RYGB groups compared with CON. In both the SG and RYGB, leptin level was decreased compared with CON and SHAM. In the SG group, ghrelin level was lower than that in the CON and SHAM. Insulin levels were not different between groups. In conclusion, RYGB and SG increased myocardial tolerance to ischemia–reperfusion injury of non-obese, non-diabetic rats, and their infarct-limiting effect is associated with decreased leptin and ghrelin levels and increased GLP-1 level.