title: Anesthetic preconditioning attenuates mitochondrial Ca2+ overload during ischemia in Guinea pig intact hearts: reversal by 5-hydroxydecanoic acid.
abstract: Cardiac ischemia/reperfusion (IR) injury is associated with mitochondrial (m)Ca(2+) overload. Anesthetic preconditioning (APC) attenuates IR injury. We hypothesized that mCa(2+) overload is decreased by APC in association with mitochondrial adenosine triphosphate-sensitive K(+) (mK(ATP)) channel opening. By use of indo-1 fluorescence, m[Ca(2+)] was measured in 40 guinea pig Langendorff-prepared hearts. Control (CON) hearts received no treatment for 50 min before IR; APC hearts were exposed to 1.2 mM (8.8 vol%) sevoflurane for 15 min; APC + 5-hydroxydecanoate (5-HD) hearts received 200 micro M 5-HD from 5 min before to 15 min after sevoflurane exposure; and 5-HD hearts received 5-HD for 35 min. Sevoflurane was washed out for 30 min and 5-HD for 15 min before 30 min of global ischemia and 120 min of reperfusion. During ischemia, the peak m[Ca(2+)] accumulation was decreased by APC from 489 +/- 37 nM (CON) to 355 +/- 28 nM (P < 0.05); this was abolished by 5-HD (475 +/- 38 nM m[Ca(2+)]). APC resulted in improved function and reduced infarct size on reperfusion, which also was blocked by 5-HD. 5-HD pretreatment alone did not affect m[Ca(2+)] (470 +/- 34 nM) or IR injury. Thus, preservation of function and morphology on reperfusion is associated with attenuated mCa(2+) accumulation during ischemia. Reversal by 5-HD suggests that APC may be triggered by opening mK(ATP) channels.
  
  
  CONCLUSIONS
  Myocardial ischemia/reperfusion injury is associated with mitochondrial Ca(2+) overload. Mitochondrial [Ca(2+)] and function were measured in guinea pig isolated hearts. Anesthetic preconditioning attenuated mitochondrial Ca(2+) overload during ischemia, improved function, and reduced infarct size. Reversal by 5-hydroxydecanoate suggests that anesthetic preconditioning may be triggered by mitochondrial adenosine triphosphate-sensitive K channel opening.
authors.affiliation: Anesthesiology Research Laboratory, Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
authors.forename: Matthias L
authors.initials: ML
authors.lastname: Riess
authors.forename: Amadou K S
authors.initials: AK
authors.lastname: Camara
authors.forename: Enis
authors.initials: E
authors.lastname: Novalija
authors.forename: Qun
authors.initials: Q
authors.lastname: Chen
authors.forename: Samhita S
authors.initials: SS
authors.lastname: Rhodes
authors.forename: David F
authors.initials: DF
authors.lastname: Stowe
mesh_terms: D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003652:Decanoic Acids / Q000494:pharmacology*; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006880:Hydroxy Acids / Q000494:pharmacology*; D019157:Ischemic Preconditioning, Myocardial; D008738:Methyl Ethers / Q000494:pharmacology; D008929:Mitochondria, Heart / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism*; D000077149:Sevoflurane
chemical_list: D000777:Anesthetics; D003652:Decanoic Acids; D006880:Hydroxy Acids; D008738:Methyl Ethers; D000077149:Sevoflurane; C052853:5-hydroxydecanoic acid; D002118:Calcium