Pravastatin But Not Simvastatin Improves Survival and Neurofunctional Outcome After Cardiac Arrest and Cardiopulmonary Resuscitation

Visual Abstract
Highlights • In a murine model of CA and CPR, intravenous application of hydrophilic pravastatin resulted in increased survival and neurofunctional outcome. • In contrast, intravenous application of lipophilic simvastatin did not improve survival or neurofunction following CA/CPR. • Pravastatin, but not simvastatin, treatment reduced post-resuscitation pulmonary edema and augmented pulmonary function. • In vitro, pravastatin augmented endothelial cell function, whereas simvastatin induced endothelial cell apoptosis. • This study supports previous requests for an intravenous formulation of hydrophilic statins for clinical use.
Summary Cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR) is associated with high mortality and poor neurological outcome. We compared the effects of pravastatin and simvastatin on survival and neurofunction in a murine model of CA/CPR. Pravastatin, a hydrophilic statin, increased survival and neurofunction during a 28-day follow-up period. This therapy was associated with improved pulmonary function, reduced pulmonary edema, and increased endothelial cell function in vitro. In contrast, lipophilic simvastatin did not modulate survival but increased pulmonary edema and impaired endothelial cell function. Although pravastatin may display a therapeutic option for post-CA syndrome, the application of simvastatin may require re-evaluation.