Cardioprotection Via Activation of Protein Kinase C-δ Depends on Modulation of the Reverse Mode of the Na + /Ca 2+ Exchanger

Abstract

Background— Pretreatment with the volatile anesthetic sevoflurane protects cardiomyocytes against subsequent ischemic episodes caused by a protein kinase C (PKC)-δ mediated preconditioning effect. Sevoflurane directly modulates cardiac Ca ²⁺ handling, and because Ca ²⁺ also serves as a mediator in other cardioprotective signaling pathways, possible involvement of the Na ⁺ /Ca ²⁺ exchanger (NCX) in relation with PKC-δ in sevoflurane-induced cardioprotection was investigated. Methods and Results— Isolated right ventricular rat trabeculae were subjected to simulated ischemia and reperfusion (SI/R), consisting of superfusion with hypoxic glucose-free buffer for 40 minutes after rigor development, followed by reperfusion with normoxic glucose containing buffer. Preconditioning with sevoflurane before SI/R improved isometric force development during contractile recovery at 60 minutes after the end of hypoxic superfusion (83±7% [sevo] versus 57±2% [SI/R];n=8; P 643 as determined by western blot analysis was not affected by sevoflurane. Conclusions— Sevoflurane-induced cardioprotection depends on the NCX preceding PKC-δ translocation presumably via increased NCX-mediated Ca ²⁺ influx. This may suggest that increased myocardial Ca ²⁺ load triggers the cardioprotective signaling cascade elicited by volatile anesthetic agents similar to other modes of preconditioning.