Preconditioning with sevoflurane reduces changes in nicotinamide adenine dinucleotide during ischemia-reperfusion in isolated hearts: reversal by 5-hydroxydecanoic acid.
BACKGROUND
Ischemia causes an imbalance in mitochondrial metabolism and accumulation of nicotinamide adenine dinucleotide (NADH). We showed that anesthetic preconditioning (APC), like ischemic preconditioning, improved mitochondrial NADH energy balance during ischemia and improved function and reduced infarct size on reperfusion. Opening adenosine triphosphate-sensitive potassium (K(atp)) channels may be involved in triggering APC. The authors tested if effects of APC on NADH concentrations before, during, and after ischemia are reversible by 5-hydroxydecanoate (5-HD), a putative mitochondrial K channel blocker.


METHODS
Nicotinamide adenine dinucleotide fluorescence was measured in 60 guinea pig Langendorff-prepared hearts assigned into five groups: (1) no treatment before ischemia; (2) APC by exposure to 1.3 mm sevoflurane for 15 min; (3) 200 microm 5-HD from 5 min before to 15 min after sevoflurane exposure; (4) 35 min 5-HD alone; and (5) no treatment and no ischemia. Sevoflurane was washed out for 30 min, and 5-HD for 15 min, before 30-min ischemia and 120-min reperfusion.


RESULTS
Nicotinamide adenine dinucleotide was reversibly increased during sevoflurane exposure before ischemia, and the increase and rate of decline in NADH during ischemia were reduced after APC. 5-HD abolished these changes in NADH. On reperfusion, function was improved and infarct size reduced after APC compared with other groups.


CONCLUSIONS
Anesthetic preconditioning was evidenced by improved mitochondrial bioenergetics as assessed from NADH concentrations during ischemia and by attenuated reperfusion injury. Reversal of APC by bracketing sevoflurane exposure with 5-HD suggests that APC is triggered by mitochondrial K channel opening or, alternatively, by attenuated mitochondrial respiration without direct involvement of mitochondrial K channel opening.
Riess
Matthias L
ML
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Novalija
Enis
E
Camara
Amadou K S
AK
Eells
Janis T
JT
Chen
Qun
Q
Stowe
David F
DF
D018528:ATP-Binding Cassette Transporters; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003652:Decanoic Acids / Q000494:pharmacology; D005453:Fluorescence; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006880:Hydroxy Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D054086:KATP Channels; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009243:NAD / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D024661:Potassium Channels, Inwardly Rectifying; D000077149:Sevoflurane; D016277:Ventricular Function, Left / Q000187:drug effects
D018528:ATP-Binding Cassette Transporters; D018685:Anesthetics, Inhalation; D003652:Decanoic Acids; D006880:Hydroxy Acids; D054086:KATP Channels; D008738:Methyl Ethers; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D009243:NAD; D000077149:Sevoflurane; C052853:5-hydroxydecanoic acid