Atorvastatin reduces infarct size in an isolated rat heart model by activating pro-survival kinases

Statins activate the PI3-kinase/Akt pathway, the pro-survival pathway. We therefore hypothesized that statins could reduce infarct size if used as a preconditioning mimetic. Isolated rat hearts were stabilized for 35 minutes on a Langerndoff apparatus during which time they received 50 mu mol atorvastatin for 10 minutes followed by 10 minutes of washout prior to ischemia/reperfusion, (Group 2). There were 3 further groups; Group I received 10 minutes of vehicle followed by washout; Group 3 received atorvastatin with wortmannin, the PI3-kinase inhibitor, and Group 4 received wortmannin alone. Atorvastatin was found to reduce infarct size significantly, infarct to risk (I/R) ratio decreasing from 44.3%+/- 2.5% to 22.2%+/- 6.6%. This protective effect was abrogated by the PI3K inhibitor wortmannin I/R ratio 53.0% +/- 2.6%). Wortmannin had no effect on infarct size (I/R ratio 58.0%+/- 6.3%). Atorvastatin given as a preconditioning mimetic reduces infarct via the PI3-kinase signalling pathway.