Ubiquitous protective effects of cyclosporine A in preventing cardiac arrest-induced multiple organ failure

International audienceOpening of the mitochondrial permeability transition pore (mPTP) appears to be a pivotal event in myocardial ischemia-reperfusion (I/R) injury. Resuscitated cardiac arrest (CA) leads to the post-CA syndrome that encompasses, not only myocardial dysfunction, but also brain injury, failure of other organs (kidney, liver, or lung), and systemic response to I/R. We aimed to determine whether cyclosporine A (CsA) might prevent multiple organ failure following CA through a ubiquitous mPTP inhibition in each distant vital organ. Anesthetized New Zealand White rabbits were subjected to 15 min of CA and 120 min of reperfusion. At the onset of resuscitation, the rabbits received CsA, its non-immunosuppressive derivative NIM811, or vehicle (controls). Survival, hemodynamics, brain damage, organ injuries, and systemic I/R response were analyzed. Fresh mitochondria were isolated from the brain, heart, kidney, liver, and lung to assess both oxidative phosphorylation and permeability transition. CsA analogs significantly improved short-term survival and prevented multiple organ failure, including brain damage and myocardial dysfunction (P \textless 0.05 vs. controls). Susceptibility of mPTP opening was significantly increased in heart, brain, kidney, and liver mitochondria isolated from controls, while mitochondrial respiration was impaired (P \textless 0.05 vs. sham). CsA analogs prevented these mitochondrial dysfunctions (P \textless 0.05 vs. controls). These results suggest that CsA and NIM811 can prevent the post-CA syndrome through a ubiquitous mitochondrial protective effect at the level of each major distant organ

Short- and long-term outcomes in onco-hematological patients admitted to the intensive care unit with classic factors of poor prognosis

International audienceAlthough the overall mortality of patients admitted to intensive care units (ICU) with hematological malignancy has decreased over the years, some groups of patients still have low survival rates. We performed a monocentric retrospective study including all patients with hematological malignancy in a ten-year period, to identify factors related to the outcome for the whole cohort and for patients with allogeneic hematopoietic stem cell transplantation (HSCT), neutropenia, or those requiring invasive mechanical ventilation (IMV). A total of 418 patients with acute leukemia (n=239; 57%), myeloma (n=69; 17%), and lymphoma (n=53; 13%) were studied. Day-28 and 1-year mortality were 49% and 72%, respectively. The type of disease was not associated with outcome. The disease status was independentlty associated with 1-year mortality only. Independent predictors of day-28 mortality were IMV, renal replacement therapy (RRT), and performance status. For allogeneic HSCT recipients (n=116), neutropenic patients (n=124) and patients requiring IMV (n=196), day-28 and 1-year mortality were 52%, 54%, 74% and 81%, 78%, 87%, respectively. Multivariate analysis showed that IMV and RRT for allogeneic HSCT recipients, performance status and IMV for neutropenic patients, and RRT for patients requiring IMV were independently associated with short-term mortality (p\textless0.05).These results suggest that IMV is the strongest predictor of mortality in hematological patients admitted to ICUs, whereas allogeneic HSCT and neutropenia do not worsen their short-term outcome