Abstract 14: A Novel Pharmacologic Peptide Improved Survival And Neurologic Outcomes After Swine PEA

Abstract

Introduction: Successful outcomes following cardiac arrest and CPR are between 5 and 15%. No pharmacologic agent has been shown to improve survival with good neurologic function. A pharmacologic agent that favorably influences heart and brain metabolism following arrest would be ideal. Our group has produced a peptide, TAT-PHLPP9c, that enhances the activity of Akt by inhibiting PH domain leucine-rich repeat phosphatase (PHLPP). Activation of this pathway prevents cardiac stunning and cerebral edema by limiting the release of taurine and glutamate, respectively. Hypothesis: Neurologic outcomes following PEA arrest in swine will be improved by the administration of TAT-PHLPP9c during CPR. Methods: 24 female pigs (30-35 kg) were anesthetized, mechanically ventilated, and catheterized. Pulseless electrical activity (PEA) was induced by inflating balloons at proximal positions in the left anterior descending and right coronary arteries to full occlusion. After an average PEA period of 7 minutes, ACLS was initiated with mechanical ventilation and vest CPR. For the controls (n=12), boluses of 0.5 mg epinephrine were administered via the venous line after one and three minutes of support. For the peptide treated animals (n=12), boluses of 7.5 mg/kg TAT-PHLPP9c were also given at one and three minutes of CPR. The balloons were deflated and removed after two minutes of support. ACLS continued until ROSC was achieved. Animals were recovered post-anesthesia and classified as neurologically intact or not intact based on behavior norms for healthy pigs. Animals with ROSC that were neurologically intact were survived overnight. Results: ROSC was more common in the peptide group, but this difference was not significant (8 control versus 12 peptide, P=0.0932). Survival was significantly more frequent in the peptide group (0 control vs. 11 peptide, P<0.00001), and all survivors were neurologically intact. Conclusion: Peptide administration during CPR is promising as a means of improving survival and neurologic outcomes following PEA arrest.