title: Improved mitochondrial bioenergetics by anesthetic preconditioning during and after 2 hours of 27 degrees C ischemia in isolated hearts.
abstract: We examined if sevoflurane given before cold ischemia of intact hearts (anesthetic preconditioning, APC) affords additional protection by further improving mitochondrial energy balance and if this is abolished by a mitochondrial KATP blocker. NADH and FAD fluorescence was measured within the left ventricular wall of 5 groups of isolated guinea pig hearts: (1) hypothermia alone; (2) hypothermia+ischemia; (3) APC (4.1% sevoflurane)+cold ischemia; (4) 5-HD+cold ischemia, and (5) APC+5-HD+cold ischemia. Hearts were exposed to sevoflurane for 15 minutes followed by 15 minutes of washout at 37 degrees C before cooling, 2 hours of 27 degrees C ischemia, and 2 hours of 37 degrees C reperfusion. The KATP channel inhibitor 5-HD was perfused before and after sevoflurane. Ischemia caused a rapid increase in NADH and a decrease in FAD that waned over 2 hours. Warm reperfusion led to a decrease in NADH and an increase in FAD. APC attenuated the changes in NADH and FAD and further improved postischemic function and reduced infarct size. 5-HD blocked the cardioprotective effects of APC but not APC-induced alterations of NADH and FAD. Thus, APC improves redox balance and has additive cardioprotective effects with mild hypothermic ischemia. 5-HD blocks APC-induced cardioprotective effects but not improvements in mitochondrial bioenergetics. This suggests that mediation of protection by KATP channel opening during cold ischemia and reperfusion is downstream from the APC-induced improvement in redox state or that these changes in redox state are not attenuated by KATP channel antagonism.
authors.affiliation: Anesthesiology Research Laboratory, Department of Anesthesiology, Medical College of Wisconsin, and Veterans Affairs Medical Center, Milwaukee, Wisconsin 53226, USA.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: An
authors.forename: Amadou K S
authors.initials: AK
authors.lastname: Camara
authors.forename: Matthias L
authors.initials: ML
authors.lastname: Riess
authors.forename: Samhita S
authors.initials: SS
authors.lastname: Rhodes
authors.forename: Srinivasan G
authors.initials: SG
authors.lastname: Varadarajan
authors.forename: David F
authors.initials: DF
authors.lastname: Stowe
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000187:drug effects; D000777:Anesthetics / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D054086:KATP Channels; D008738:Methyl Ethers / Q000494:pharmacology; D008929:Mitochondria, Heart / Q000187:drug effects*; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D000077149:Sevoflurane; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D018528:ATP-Binding Cassette Transporters; D000777:Anesthetics; D018685:Anesthetics, Inhalation; D054086:KATP Channels; D008738:Methyl Ethers; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D009243:NAD; D005182:Flavin-Adenine Dinucleotide; D000077149:Sevoflurane