Abstract 257: Plasma PBEF Correlates With Cardiac Arrest Outcome in Mice and Humans

Abstract

Introduction: Pre-B-cell colony enhancing factor (PBEF) is a 52 kDa cytokine that has recently been associated with cardiac dysfunction and insulin resistance in heart failure patients. Such cardiac dysfunction and insulin resistance are also seen after clinical cardiac arrest (CA) and are associated with later death and poor neurologic outcome. We hypothesized that elevated plasma PBEF could serve as a marker of tissue injury in both patients and mice after sudden cardiac arrest. Methods: Human plasma samples after CA resuscitation were collected at four centers of excellence in the care of CA patients (Virginia Commonwealth University, Beth Israel Deaconess Medical Center, University of Pennsylvania and University of Pittsburgh). All patients studied received standardized post-CA care that for most patients included therapeutic hypothermia (TH). Blood was collected within 90 min after return of spontaneous circulation (ROSC) and at 12, 24, and 48 h post-ROSC and plasma PBEF measured by ELISA. Mouse plasma samples taken after KCl-induced CA for 8 min in mice treated with TH versus normothermia after CPR, and in Akt1 partial knockout mice that fail to demonstrate TH protection. Results: CA patients who survived to hospital discharge (n=12) had serial PBEF concentrations that dropped by 40% within 12 h post-ROSC. In both human and mouse samples, the highest PBEF concentrations were seen within the first hour after ROSC. In human samples, plasma PBEF exceeded ~240 ng/ml, well above the PBEF concentrations associated with acute decompensation of heart failure and acute myocardial infarction. In CA patients who did not survive to hospital discharge (n=12), the fall-off of plasma PBEF was less than 20% from the initial level seen. After mouse CA, plasma PBEF at 30 min post-ROSC was significantly lower in TH mice compared to normothermic mice (p < 0.05). Conversely, it was higher in Akt1+/- mice (hypothermia non-responders), over 4-fold, compared to wild type responders (p < 0.05). Conclusions: Plasma PBEF is increased early after CA and may be associated with poor outcome. Further work is needed to test PBEF plasma clearance in cardiac arrest survivors versus non-survivors and understand the mechanism of PBEF release after CA.