The spontaneously hypertensive rat (SHR) has been used to model changes in the central nervous system associated with cognitive-related disorders. Recent human and animal studies indicate a possible relationship between cognitive deficits, insulin resistance and hypertension. We aimed to investigate whether cognitively impaired SHRs develop central and/or peripheral insulin resistance and how their cognitive performance is influenced by the animal’s sex and age as well as strains used for comparison (Wistar and Wistar-Kyoto/WKY). Three and seven-month-old SHR, Wistar, and WKY rats were studied for their cognitive performance using Morris Water Maze (MWM) and Passive Avoidance tests (PAT). Plasma glucose and insulin were obtained after oral glucose tolerance tests. Cerebral cortex, hippocampus, and striatum status of insulin-receptor (IR) β-subunit and glycogen synthase kinase-3β (GSK3β) and their phosphorylated forms were obtained via ELISA. SHRs performed poorly in MWM and PAT in comparison to both control strains but more pronouncedly compared to WKY. Females performed poorer than males and 7-month-old SHRs had poorer MWM performance than 3-month-old ones. Although plasma glucose levels remained unchanged, plasma insulin levels were significantly increased in the glucose tolerance test in 7-month-old SHRs. SHRs demonstrated reduced expression and increased activity of IRβ-subunit in cerebral cortex, hippocampus, and striatum with different regional changes in phospho/total GSK3β ratio, as compared to WKYs. Results indicate that cognitive deficits in SHRs are accompanied by both central and peripheral insulin dysfunction, thus allowing for the speculation that SHRs might additionally be considered as a model of insulin resistance-induced type of dementia.

Donation after circulatory death (DCD) has the potential to expand the lung donor pool. We aimed to assess whether DCD affected the need for perioperative extracorporeal membrane oxygenation (ECMO) and perioperative outcomes in lung transplantation (LTx) as compared to donation after brain death (DBD). All consecutive LTx performed between April 2017 and March 2019 at our tertiary centre were analysed. Donor and recipient preoperative characteristics, utilization of ECMO and perioperative clinical outcomes were compared between DCD and DBD LTx. Multivariate models (frequentist and Bayes) were fitted to evaluate an independent effect of DCD on the intra‐ and postoperative need for ECMO. Out of 105 enrolled patients, 25 (23.8%) were DCD LTx. Donors’ and preoperative recipients’ characteristics were comparable between the groups. Intraoperatively, mechanical circulatory support (MCS) was more common in DCD LTx (56.0% vs. 36.2%), but the adjusted difference was minor (RR=1.16, 95%CI 0.64‐2.12; p=0.613). MCS duration, first and second lung ischemia time were longer in the DCD group. Postoperatively, DCD recipients more commonly required ECMO (32.0% vs. 7.5%) and the difference remained considerable after adjustment for the pre‐ and intraoperative covariates: RR=4.11 (95%CI 0.95‐17.7), p=0.058, Bayes RR=4.15 (95%CrI 1.28‐13.0). Sensitivity analyses (two DCD‐DBD matching procedures) supported a higher risk of postoperative ECMO need in DCD patients. Incidence of delayed chest closure, postoperative chest drainage, and renal replacement therapy was higher in the DCD group. Early postoperative outcomes after DCD LTx appeared generally comparable to those after DBD LTx. DCD was associated with a higher need for postoperative ECMO which could influence clinical outcomes. However, as the DCD group had a significantly higher use of EVLP with more common ECMO preoperatively, this might have contributed to worse outcomes in the DCD group.