Insufficient Production of Urinary Trypsin Inhibitor for Neutrophil Elastase Release After Cardiac Arrest

Abstract

Running headInsufficient of UTI following cardiac arrest out-of-hospital cardiac arrests that were admitted to our intensive care unit after return of spontaneous circulation (ROSC). The twenty-two patients who died within 3 days after ROSC were defined as nonsurvivors. The fourteen patients who survived for more than 3 days after ROSC were defined as survivors. Eight healthy volunteers served as control group. Daily plasma levels of NE, UTI, and TNF-were measured from days 1 to 5 after ROSC. Persistently high levels of TNF-and NE were observed in both the survivors and nonsurvivors. In the two groups, the levels of UTI were significantly high and increased as time progressed. NE/UTI ratios were significantly higher in the nonsurvivors than in NE = neutrophil elastase ROSC = return of spontaneous circulation SOFA = Sequential Organ Failure Assessment TNF- = tumor necrosis factor- UTI = urinary trypsin inhibitor 3 the survivors, especially on day 1. The nonsurvivors showed statistically higher scores according to the Sequential Organ Failure Assessment and they also had more organ failure than the survivors. In conclusion, an insufficient production of UTI for NE release and persistent high levels of TNF- may contribute to the pathogenesis of post-resuscitation syndrome following out-of-hospital cardiac arrest.

Disseminated intravascular coagulation in cardiac arrest and resuscitation

“…Neutrophil activation, as measured according to neutrophil elastase (neutrophil elastase and α 1 ‐protease inhibitor complex) and soluble L‐selectin levels, was confirmed from the time of CPR to 24 hours after successful ROSC . The levels of neutrophil elastase were higher in patients without ROSC than in those in whom resuscitation was achieved, and were correlated with the duration of cardiac arrest, which suggests that prolonged hypoxia and ischemia induce greater activation of neutrophils. Neutrophil elastase has been implicated in neutrophil‐mediated tissue and endothelial injury .…”

“…High levels of TNF‐α and IL‐6 have been repeatedly confirmed in patients after cardiac arrest and resuscitation from immediately after arrival at the ED to several days later . The levels of both cytokines were higher in patients with a longer low‐flow time (time of cardiopulmonary resuscitation [CPR]), patients with catecholamine use, and non‐survivors, and contributed to the development of SIRS.…”

Coagulofibrinolytic Changes in Patients with Post-cardiac Arrest Syndrome

“…Inflammatory cytokines induce the expression of tissue factor in endothelial cells and monocytes ( 21 ). High levels of tumor necrosis factor-α ( 3 , 22 ), interleukin (IL)-6 ( 3 , 11 ), and IL-8 ( 3 , 23 ) have been found in PCAS patients. Thrombin produced in this process not only converts fibrinogen to fibrin but also works as a potent pro-inflammatory factor through binding to protease-activated receptors ( 24 ), suggesting that systemic inflammation and coagulation activation shore up each other ( 11 ).…”

Disseminated intravascular coagulation with the fibrinolytic phenotype predicts the outcome of patients with out-of-hospital cardiac arrest

“…Inflammatory cytokine-initiated activation of tissue-factor-dependent coagulation, insufficient control of the anticoagulation pathways, and plasminogen activator inhibitor-1 (PAI-1)-mediated suppression of fibrinolysis characterize the pathogenesis of DIC [ 7 ]. From the first report of DIC following cardiac arrest [ 8 ], higher levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-8 [ 4 , 9 , 10 ]; increased tissue factor levels [ 11 ]; insufficient levels of tissue factor pathway inhibitor (TFPI), antithrombin, protein C and protein S [ 4 , 11 ]; and increased PAI-1 levels [ 12 , 13 ] have been repeatedly confirmed during cardiopulmonary resuscitation (CPR) and after return of spontaneous circulation (ROSC). These changes lead to massive thrombin generation and consecutive fibrin formation [ 4 , 6 , 12 ].…”