title: Measurement of technetium-99m sestamibi signals in rats administered a mitochondrial uncoupler and in a rat model of heart failure.
abstract: BACKGROUND
  Many methods have been used to assess mitochondrial function. Technetium-99m sestamibi ((99m)Tc-MIBI), a lipophilic cation, is rapidly incorporated into myocardial cells by diffusion and mainly localizes to the mitochondria. The purpose of this study was to investigate whether measurement of (99m)Tc-MIBI signals in animal models could be used as a tool to quantify mitochondrial membrane potential at the organ level.
  
  
  RESULTS
  We analyzed (99m)Tc-MIBI signals in Sprague-Dawley (SD) rat hearts perfused with carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler known to reduce the mitochondrial membrane potential. (99m)Tc-MIBI signals could be used to detect changes in the mitochondrial membrane potential with sensitivity comparable to that obtained by two-photon laser microscopy with the cationic probe tetramethylrhodamine ethyl ester (TMRE). We also measured (99m)Tc-MIBI signals in the hearts of SD rats administered CCCP (4 mg/kg intraperitoneally) or vehicle. (99m)Tc-MIBI signals decreased in rat hearts administered CCCP, and the ATP content, as measured by (31)P magnetic resonance spectroscopy, decreased simultaneously. Next, we administered (99m)Tc-MIBI to Dahl salt-sensitive rats fed a high-salt diet, which leads to hypertension and heart failure. The (99m)Tc-MIBI signal per heart tissue weight was inversely correlated with heart weight, cardiac function, and the expression of atrial natriuretic factor, a marker of heart failure, and positively correlated with the accumulation of labeled fatty acid analog. The (99m)Tc-MIBI signal per liver tissue weight was lower than that per heart tissue weight.
  
  
  CONCLUSIONS
  Measurement of (99m)Tc-MIBI signals can be an effective tool for semiquantitative investigation of cardiac mitochondrial membrane potential in the SD rat model by using a chemical to decrease the mitochondrial membrane potential. The (99m)Tc-MIBI signal per heart tissue weight was inversely correlated with the severity of heart failure in the Dahl rat model.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kawamoto
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Cardiovascular Center, Kitano Hospital, The Tazuke Kofukai Medical Research Institute, Osaka, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Shioi
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Okuda
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Tsuneaki
authors.initials: T
authors.lastname: Kawashima
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yodo
authors.initials: Y
authors.lastname: Tamaki
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Niizuma
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Tanada
authors.affiliation: Division of Cardiology, Gifu University, Graduate School of Medicine, Gifu, Japan.
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.affiliation: Department of Systems Science, Graduate School of Informatics, Kyoto University, Kyoto, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Narazaki
authors.affiliation: Department of Systems Science, Graduate School of Informatics, Kyoto University, Kyoto, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsuda
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000818:Animals; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D004195:Disease Models, Animal; D006333:Heart Failure / Q000175:diagnosis*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008929:Mitochondria, Heart / Q000378:metabolism; D061209:Proton Ionophores / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017256:Technetium Tc 99m Sestamibi
chemical_list: D061209:Proton Ionophores; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D017256:Technetium Tc 99m Sestamibi