Statins (HMG-CoA reductase inhibitors) exert numerous pleiotropic effects and have been shown to attenuate ischemic injury in different rodent models of cerebral focal ischemia. Few studies have examined the effect of statins on post cardiac arrest syndrome. This study conducted cardiac arrest and cardiopulmonary resuscitation (CA/CPR) in mice and tested the hypothesis that intravenous statin after CPR improves survival rate and neurological outcomes.
Methods:
Adult male mice (20-26 g) were subjected to CA induced by intravenous (IV) KCL. After 8 min of CA, CPR was initiated with IV epinephrine, ventilation with 100% oxygen and chest compressions (rate 300/min). At 1 hr after return of spontaneous circulation, mice were treated with either IV injection of pravastatin (3mg/kg) or vehicle. Four days after CA/CPR, neurobehavioral assessments were performed and brains were removed for histological evaluation in hippocampus and caudateputamen.
Results:
No difference was found between two groups in body weight, duration of CPR and dose of epinephrine. Survival rate at 4 days after CPR was significantly higher in pravastatin group compared with vehicle group (66.7%; n=24 vs 48.4%; n=33). Neurobehavioral scores in pravastatin group were better than vehicle group at 2 to 4 days after CPR. Body weight loss in vehicle group at 4 days after CPR was higher than pravastatin group (-19.4±1.8% vs -13.4±2.0%), which indicates loss of feeding activity. Histological damages in hippocampus and caudateputamen were not statistically different between two groups (pravastatin: 23.8±7.0% vs vehicle: 35.2±9.2% in hippocampus) (pravastatin: 49.4±7.2% vs vehicle: 60.5±7.8% in caudateputamen). All values are presented as mean±SEM.
Conclusions:
Single IV injection of pravastatin after CA improved short-term survival and neurobehavioral score in the mouse experimental CA model. Neuronal damage in the brain region was comparable to vehicle group. These data suggest that pravastatin given after CA would be beneficial in the post resuscitation phase via systemic pleiotropic effects such as anti inflammatory response and improved vascular reactivity.
Methylene blue added to a hypertonic–hyperoncotic solution increases short-term survival in experimental cardiac arrest*
