Abstract 223: PBEF/Nampt Protects Against Mouse Sudden Cardiac Arrest Injury
Introduction: Pre-B-cell colony-enhancing factor or nicotinamide phosphoribosyltransferase (PBEF/Nampt) is critical for NAD+ biosynthesis and metabolism. Given the important role of early metabolic recovery to sudden cardiac arrest (SCA) survival, we hypothesized that PBEF/Nampt deficient mice would demonstrate worse SCA outcomes after cardiopulmonary resuscitation (CPR).
Methods: C57BL6 wild type and PBEF/Nampt+/- mice underwent 8 min of KCl-induced SCA and were monitored for 4 h survival after CPR. Heart, brain and blood PBEF/Nampt concentrations were measured by Western blot and ELISA. Tissue NAD+ concentrations and blood markers of metabolic recovery including plasma lactate, glucose and insulin were measured.
Results: At baseline, heart and brain tissue levels of PBEF/Nampt were significantly decreased by 50% in PBEF/Nampt+/- mice with no change of NAD+ concentrations. By 4 h after CPR PBEF/Nampt+/- mice had worse survival, with 83% dead of cardiovascular collapse (n=18) compared to 45% of WT mice (n=11) (p < 0.05). At 4 h after CPR, heart NAD+ concentration were significantly decreased by more than 50% in PBEF/Nampt+/- mice versus WT mice (p < 0.05). Blood PBEF/Nampt was significantly increased in both WT and PBEF/Nampt+/- mice compared to sham controls, with PBEF/Nampt+/- mice demonstrating lower blood PBEF/Nampt concentrations and higher plasma glucose, insulin and lactate concentrations.
Conclusion: PBEF/Nampt tissue deficiency decreases successful cardiovascular resuscitation within 4 h after SCA and CPR. Early survival after SCA is related to tissue NAD+ concentrations in the heart and blood PBEF/Nampt concentrations by 4 h after CPR. The role of tissue PBEF/Nampt as a possible therapeutic target after SCA warrants further study.
Author Disclosures: J. Li: None. H. Wang: None. Y. Qian: None. C. Lee: None. X. Zhu: None. R. Bunney: None. J. Chen: None. R. Machado: None. J.N. Garcia: None. T. Vanden Hoek: None.
- © 2014 by American Heart Association, Inc.