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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Anesthetics, Inhalation, Aniline Compounds, Animals, Calcium Signaling, Cardiotonic Agents, Enzyme Activation, Glucose, Heart Ventricles, In Vitro Techniques, Ischemic Preconditioning, Myocardial, Male, Methyl Ethers, Myocardial Ischemia, Myocardial Reperfusion Injury, Phenyl Ethers, Phosphorylation, Phosphoserine, Protein Kinase C-delta, Protein Processing, Post-Translational, Protein Transport, Rats, Rats, Wistar, Sarcolemma, Sevoflurane, Signal Transduction, Sodium-Calcium Exchanger, Thiourea.
user
Does cardioprotection via activation of protein kinase C-delta depend on modulation of the reverse mode of the Na+/Ca2+ exchanger? Context: Pretreatment with the volatile anesthetic sevoflurane protects cardiomyocytes against subsequent ischemic episodes caused by a protein kinase C (PKC)-delta mediated preconditioning effect. Sevoflurane directly modulates cardiac Ca2+ handling, and because Ca2+ also serves as a mediator in other cardioprotective signaling pathways, possible involvement of the Na+/Ca2+ exchanger (NCX) in relation with PKC-delta in sevoflurane-induced cardioprotection was investigated. 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<0.01). Inhibition of the reverse mode of the NCX by KB-R7943 (10 micromol/L) or SEA0400 (1 micromol/L) during preconditioning attenuated the protective effect of sevoflurane. KB-R7943 and SEA0400 did not have intrinsic effects on the contractile recovery. Furthermore, inhibition of the NCX in trabeculae exposed to sevoflurane reduced sevoflurane-induced PKC-delta translocation toward the sarcolemma, as demonstrated by digital imaging fluorescent microscopy. The degree of PKC-delta phosphorylation at serine643 as determined by western blot analysis was not affected by sevoflurane.
assistant
Sevoflurane-induced cardioprotection depends on the NCX preceding PKC-delta translocation presumably via increased NCX-mediated Ca2+ influx. This may suggest that increased myocardial Ca2+ load triggers the cardioprotective signaling cascade elicited by volatile anesthetic agents similar to other modes of preconditioning. Final Decision: yes