Co-dependence of the neural and humoral pathways in the mechanism of remote ischemic conditioning

The cardioprotection afforded by remote ischaemic conditioning (RIC) is mediated via a complex mechanism involving sensory afferent nerves, the vagus nerve, and release of a humoral blood-borne factor. However, it is unknown whether release of the protective factor depends on vagal activation or occurs independently. This study aimed to evaluate the co-dependence of the neural and humoral pathways of RIC, focussing on the vagus nerve and intrinsic cardiac ganglia. In the first study, anesthetised rats received bilateral cervical vagotomy or sham-surgery immediately prior to RIC (4 × 5 min limb ischemia-reperfusion) or sham-RIC. Venous blood plasma was dialysed across a 12-14 kDa membrane and dialysate perfused through a naïve-isolated rat heart prior to 35-min left anterior descending ischemia and 60-min reperfusion. In the second study, anesthetised rats received RIC (4 × 5-min limb ischemia-reperfusion) or control (sham-RIC). Dialysate was prepared and perfused through a naïve-isolated rat heart in the presence of the ganglionic blocker hexamethonium or muscarinic antagonist atropine, prior to ischemia-reperfusion as above. Dialysate collected from RIC-treated rats reduced infarct size in naïve rat hearts from 40.7 ± 6.3 to 23.7 ± 3.1 %, p < 0.05. Following bilateral cervical vagotomy, the protection of RIC dialysate was abrogated (42.2 ± 3.2 %, p < 0.05 vs RIC dialysate). In the second study, the administration of 50-μM hexamethonium (45.8 ± 2.5 %) or 100-nM atropine (36.5 ± 3.4 %) abrogated the dialysate-mediated protection. Release of a protective factor following RIC is dependent on prior activation of the vagus nerve. In addition, this factor appears to induce cardioprotection via recruitment of intrinsic cardiac ganglia

Study of in vivo catheter biofilm infections using pediatric central venous catheter implanted in rat

International audienceVenous access catheters used in clinics are prone to biofilm contamination, contributing to chronic and nosocomial infections. So far, biofilm physiology was mostly studied in vitro, due to a relative lack of clinically relevant in vivo models. Here, we provide a relevant protocol of totally implantable venous access port (TIVAP) implanted in rats. This model recapitulates all phenomena observed in clinic and allows studying bacterial biofilm development and physiology. After TIVAP implantation and inoculation with luminescent pathogens, in vivo biofilm formation can be monitored in situ and biofilm biomass can be recovered from contaminated TIVAP and organs. We used this protocol to study host responses to biofilm-infection, to evaluate preventive and curative anti-biofilm strategies, and to study fundamental biofilm properties. For this procedure, one should expect ~3h00 of hands-on time including the implantation in one rat followed by in situ luminescence monitoring and bacterial load estimation