Subcutaneous cardioverter defibrillator has longer time to therapy but is less cardiotoxic than transvenous cardioverter defibrillator. Study carried out in a preclinical porcine model.

Aims: Totally subcutaneous implantable cardioverter defibrillator (S-ICD) delivers higher shock energy and can have longer time to therapy compared to transvenous implantable cardioverter defibrillator (T-ICD). Aim of the study was to compare time to therapy and to investigate cardiac, cerebral and systemic injuries of S-ICD and T-ICD shocks delivered after ventricular fibrillation (VF) induction. Methods and results: Fourteen pigs were randomly implanted with a S-ICD (n = 7) or a T-ICD (n = 7). Five VF episodes were induced in each pig. For each VF episode, up to two shocks could be delivered by the T-ICD or the S-ICD to terminate the arrhythmia. Cardiac, systemic, and cerebral toxicity were monitored. Mean time to therapy was longer in the S-ICD group compared to the T-ICD group (19[18; 23] s vs. 9 [7; 10] s; P = 0.001, respectively). High-sensitivity troponin T levels were significantly higher in the T-ICD group from 1 to 24 h after the procedure (P ≤ 0.02). Creatine phosphokinase activity levels were significantly higher in the S-ICD group, at 3, 6, and 24 h after the procedure (P ≤ 0.05). Lactate levels were not significantly different between groups. S100 protein level was similar in both groups at 1 h after the procedure and then decreased in the T-ICD group compared to the S-ICD group (P = 0.04). Conclusions: Time to therapy in S-ICD was twice as long as for T-ICD, but didn't induce relevant brain injury. Conversely, S-ICD shocks were less cardiotoxic than T-ICD shocks.

[Ischemia-reperfusion injury after kidney transplantation]. / Ischémie reperfusion en transplantation rénale.

Ischemia-reperfusion injury is an inescapable phenomenon in kidney transplantation. It combines lesional processes of biochemical origin associated with oxydative stress and of immunological origin in connection with the recruitment and activation of innate immunity cells. Histological lesions associate acute tubular necrosis and interstitial œdema, which can progress to interstitial fibrosis. The extent of these lesions depends on donor characteristics (age, expanded criteria donor, etc.) and cold ischemia time. In the short term, ischemia-reperfusion results in delayed recovery of graft function. Cold ischemia time also impacts long-term graft survival. Preclinical models, such as murine and porcine models, have furthered understanding of the pathophysiological mechanisms of ischemia-reperfusion injury. Due to its renal anatomical proximity to humans, the porcine model is relevant to assessment of the molecules administered to a donor or recipient, and also of additives to preservation solutions. Different donor resuscitation and graft perfusion strategies can be studied. In humans, prevention of ischemia-reperfusion injury is a research subject as concerns donor conditioning, additive molecules in preservation solutions, graft reperfusion modalities and choice of the molecules administered to the recipient. Pending significant advances in research, the goal is to achieve the shortest possible cold ischemia time.

Tannic Acid Improves Renal Function Recovery after Renal Warm Ischemia-Reperfusion in a Rat Model.

BACKGROUND AND PURPOSE: Ischemia-reperfusion injury is encountered in numerous processes such as cardiovascular diseases or kidney transplantation; however, the latter involves cold ischemia, different from the warm ischemia found in vascular surgery by arterial clamping. The nature and the intensity of the processes induced by ischemia types are different, hence the therapeutic strategy should be adapted. Herein, we investigated the protective role of tannic acid, a natural polyphenol in a rat model reproducing both renal warm ischemia and kidney allotransplantation. The follow-up was done after 1 week. EXPERIMENTAL APPROACH: To characterize the effect of tannic acid, an in vitro model of endothelial cells subjected to hypoxia-reoxygenation was used. KEY RESULTS: Tannic acid statistically improved recovery after warm ischemia but not after cold ischemia. In kidneys biopsies, 3h after warm ischemia-reperfusion, oxidative stress development was limited by tannic acid and the production of reactive oxygen species was inhibited, potentially through Nuclear Factor erythroid-2-Related factor 2 (NRF2) activation. In vitro, tannic acid and its derivatives limited cytotoxicity and the generation of reactive oxygen species. Molecular dynamics simulations showed that tannic acid efficiently interacts with biological membranes, allowing efficient lipid oxidation inhibition. Tannic acid also promoted endothelial cell migration and proliferation during hypoxia. CONCLUSIONS: Tannic acid was able to improve renal recovery after renal warm ischemia with an antioxidant effect putatively extended by the production of its derivatives in the body and promoted cell regeneration during hypoxia. This suggests that the mechanisms induced by warm and cold ischemia are different and require specific therapeutic strategies.