Faculty Collaboration Database

Isoflurane preconditioning uncouples mitochondria and protects against hypoxia-reoxygenation. Am J Physiol Cell Physiol 2007 May;292(5):C1583-90

Date

01/12/2007

Pubmed ID

17215328

DOI

10.1152/ajpcell.00221.2006

Scopus ID

2-s2.0-34250630083 (requires institutional sign-in at Scopus site)   75 Citations

Abstract

Ischemic cardiac injury can be substantially alleviated by exposing the heart to pharmacological agents such as volatile anesthetics before occurrence of ischemia-reperfusion. A hallmark of this preconditioning phenomenon is its memory, when cardioprotective effects persist even after removal of preconditioning stimulus. Since numerous studies pinpoint mitochondria as crucial players in protective pathways of preconditioning, the aim of this study was to investigate the effects of preconditioning agent isoflurane on the mitochondrial bioenergetic phenotype. Endogenous flavoprotein fluorescence, an indicator of mitochondrial redox state, was elevated to 195 +/- 16% of baseline upon isoflurane application in intact cardiomyocytes, indicating more oxidized state of mitochondria. Isoflurane treatment also elicited partial dissipation of mitochondrial transmembrane potential, which remained depolarized even after anesthetic withdrawal (tetramethylrhodamine fluorescence intensity declined to 83 +/- 3 and 81 +/- 7% of baseline during isoflurane exposure and washout, respectively). Mild uncoupling, with preserved ATP synthesis, was also detected in mitochondria that were isolated from animals that had been previously preconditioned by isoflurane in vivo, revealing its memory nature. These mitochondria, after exposure to hypoxia and reoxygenation, exhibited better preserved respiration and ATP synthesis compared with mitochondria from nonpreconditioned animals. Partial mitochondrial depolarization was paralleled by a diminished Ca(2+) uptake into isoflurane-treated mitochondria, as indicated by the reduced increment in rhod-2 fluorescence when mitochondria were challenged with increased Ca(2+) (180 +/- 24 vs. 258 +/- 14% for the control). In conclusion, isoflurane preconditioning elicits partial mitochondrial uncoupling and reduces mitochondrial Ca(2+) uptake. These effects are likely to reduce the extent of the mitochondrial damage after the hypoxic stress.

Author List

Ljubkovic M, Mio Y, Marinovic J, Stadnicka A, Warltier DC, Bosnjak ZJ, Bienengraeber M

MESH terms used to index this publication - Major topics in bold

Adenosine Diphosphate
Adenosine Triphosphate
Anesthetics, Inhalation
Animals
Calcium
Cell Hypoxia
Cytoprotection
Drug Administration Schedule
Energy Metabolism
Heart Ventricles
In Vitro Techniques
Isoflurane
Male
Membrane Potential, Mitochondrial
Mitochondria, Heart
Myocytes, Cardiac
Oxygen
Oxygen Consumption
Rats
Rats, Wistar
Reactive Oxygen Species