RESUMEN
BACKGROUND: Hyperoxia is common during liver transplantation (LT), without being supported by any guidelines. Recent studies have shown the potential deleterious effect of hyperoxia in similar models of ischemia-reperfusion. Hyperoxia after graft reperfusion during orthotopic LT could increase lactate levels and worsen patient outcomes. METHODS: We conducted a retrospective and monocentric pilot study. All adult patients who underwent LT from 26 July 2013 to 26 December 2017 were considered for inclusion. Patients were classified into two groups according to oxygen levels before graft reperfusion: the hyperoxic group (PaO2 > 200 mmHg) and the nonhyperoxic group (PaO2 < 200 mmHg). The primary endpoint was arterial lactatemia 15 min after graft revascularization. Secondary endpoints included postoperative clinical outcomes and laboratory data. RESULTS: A total of 222 liver transplant recipients were included. Arterial lactatemia after graft revascularization was significantly higher in the hyperoxic group (6.03 ± 4 mmol/L) than in the nonhyperoxic group (4.81 ± 2 mmol/L), p < 0.01. The postoperative hepatic cytolysis peak, duration of mechanical ventilation and duration of ileus were significantly increased in the hyperoxic group. CONCLUSIONS: In the hyperoxic group, the arterial lactatemia, the hepatic cytolysis peak, the mechanical ventilation and the postoperative ileus were higher than in the nonhyperoxic group, suggesting that hyperoxia worsens short-term outcomes and could lead to increase ischemia-reperfusion injury after liver transplantation. A multicenter prospective study should be performed to confirm these results.
RESUMEN
Among extracellular vesicles, leukocyte-derived microvesicles (LMVs) have emerged as complex vesicular structures. Primarily identified as procoagulant entities, they were more recently ascribed to plasmin generation capacity (MV-PGC). The objectives of this work were (1) to develop a new hybrid bio-assay combining the specific isolation of LMVs and measurement of their PGC, and compare its performance to the original method based on centrifugation, (2) to validate MV-PGC in septic shock, combining increased levels of LMVs and fibrinolytic imbalance. Using plasma sample spiked with LMVs featuring different levels of PGC, we demonstrated that CD15-beads specifically extracted LMVs. The MV dependency of the test was demonstrated using electron microscopy, high speed centrifugation, nanofiltration and detergent-mediated solubilization and the MV-PGC specificity using plasmin-specific inhibitors, or antibodies blocking elastase or uPA. Thanks to a reaction booster (ε-ACA), we showed that the assay was more sensitive and reproducible than the original method. Moreover, it exhibited a good repeatability, inter-operator and inter-experiment reproducibility. The new immunomagnetic bio-assay was further validated in patients with septic shock. As a result, we showed that MV-PGC values were significantly lower in septic shock patients who died compared to patients who survived, both at inclusion and 24 h later (1.4 [0.8-3.0] vs 3.1 [1.7-18] A405 × 10-3/min, p = 0.02; 1.4 [1-1.6] vs 5.2 [2.2-16] A405 × 10-3/min, p = 0.004). Interestingly, combining both MV-PGC and PAI-1 in a ratio significantly improved the predictive value of PAI-1. This strategy, a hybrid capture bioassay to specifically measure LMV-PGC using for the first time, opens new perspectives for measuring subcellular fibrinolytic potential in clinical settings with fibrinolytic imbalance.