PLoS ONE (Jan 2015)

Measurement of technetium-99m sestamibi signals in rats administered a mitochondrial uncoupler and in a rat model of heart failure.

  • Akira Kawamoto,
  • Takao Kato,
  • Tetsuo Shioi,
  • Junji Okuda,
  • Tsuneaki Kawashima,
  • Yodo Tamaki,
  • Shinichiro Niizuma,
  • Yohei Tanada,
  • Genzou Takemura,
  • Michiko Narazaki,
  • Tetsuya Matsuda,
  • Takeshi Kimura

DOI
https://doi.org/10.1371/journal.pone.0117091
Journal volume & issue
Vol. 10, no. 1
p. e0117091

Abstract

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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. METHODS AND 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. CONCLUSION: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.