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PEDIATRIC ANESTHESIA

Sevoflurane Preconditioning Limits Intracellular/Mitochondrial Ca²⁺ in Ischemic Newborn Myocardium

Hong Liu, MD^*, Lianguo Wang, MD, Matt Eaton, BS, and Saul Schaefer, MD

*Department of Anesthesiology and Pain Medicine; and Department of Internal Medicine, Division of Cardiovascular Medicine, University of California Davis Medical Center, Sacramento, California

Address correspondence and reprint requests to Hong Liu, MD, Department of Anesthesiology and Pain Medicine, University of California Davis Medical Center, 4150 V St., Suite 1200, Sacramento, CA 95817. Address e-mail to hualiu{at}ucdavis.edu.

Sevoflurane preconditioning (SPC) in adult hearts reduces myocardial ischemia/reperfusion (I/R) injury, an effect that may be mediated by reductions in intracellular Ca²⁺ ([Ca²⁺]_i) and/or mitochondrial Ca²⁺ ([Ca²⁺]_m) accumulation during ischemia and reperfusion. Because the physiology, pharmacology, and metabolic responses of the newborn differ from adults, we tested the hypothesis that SPC protects newborn myocardium by limiting [Ca²⁺]_i and [Ca²⁺]_m by a K_ATP channel-dependent mechanism. Fluorescence spectrofluorometry and nuclear magnetic resonance spectroscopy were used to measure [Ca²⁺]_i, [Ca²⁺]_m, and adenosine triphosphate (ATP) in 4- to 7-day-old Langendorff-perfused rabbit hearts. Three experimental groups were used to study the effect of SPC on [Ca²⁺]_m/[Ca²⁺]_i, ATP, as well as hemodynamics and ischemic injury. The role of mitochondrial K_ATP channels was assessed by exposing the SPC hearts to the mitochondrial K_ATP channel blocker 5-hydroxydecanoic acid. Our results show that SPC significantly decreased [Ca²⁺]_i and [Ca²⁺]_m during I/R, as well as decreased creatine kinase release during reperfusion and resulted in higher ATP. 5-Hydroxydecanoic acid abolished the effect of SPC on [Ca²⁺], hemodynamics, ATP, and creatine kinase release. In conclusion, decreased [Ca²⁺]_i and [Ca²⁺]_m observed with SPC is associated with greater ATP recovery as well as diminished cell injury. Mitochondrial K_ATP channel blockade attenuates the SPC effect during I/R, suggesting that these channels are involved in the protective effects of SPC in the newborn.

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