Isoflurane preconditioning protects against ischemia-reperfusion injury partly by attenuating cytochrome c release from subsarcolemmal mitochondria in isolated rat hearts

Acta Pharmacol Sin. 2005 Jul;26(7):813-20. doi: 10.1111/j.1745-7254.2005.00117.x.

Abstract

Aim: To examine if isoflurane preconditioning can attenuate ischemia/reperfusion injury by reducing cytochrome c release from inner mitochondrial membrane.

Methods: Isolated hearts of Sprague-Dawley rats were perfused on Langendorff apparatus. Hearts were randomly assigned to a non-treated group (CON group, n=12) or three isoflurane preconditioning groups (0.5% ISC group, 1.0% ISC group, and 2.0% ISC group; n=12). In the latter three groups, isoflurane was given at concentrations of 0.5%, 1.0%, and 2.0% for 15 min with 15-min washout before 30-min ischemia. Subsarcolemmal mitochondria of the myocardium were isolated after 60-min reperfusion. Hemodynamics of the each heart was recorded, infarct size of the hearts and contents of cytosolic cytochrome or mitochondrial cytochrome c were measured at the end of reperfusion. Morphology of isolated mitochondria in the four groups was evaluated, respectively.

Results: Compared with the CON group, cytosolic cytochrome c in 0.5% ISC group, 1.0% ISC group, and 2.0% ISC group were significantly decreased along with a significant increase of mitochondrial cytochrome c. Infarct size of the hearts in the four groups were 56%+/-12%, 41%+/-12%, 32%+/-7% and 33%+/-11%, respectively. The values of the three isoflurane preconditioning groups were significantly lower than that of the CON group (P<0.05). Isoflurane exposure before ischemia can attenuate the change of morphology of mitochondria after reperfusion. The effects of 2.0% isoflurane on reducing cytochrome c release were more remarkable than 0.5% and 1.0% concentrations of isoflurane.

Conclusion: Myocardioprotective effects of isoflurane preconditioning were associated with attenuation of cytochrome c loss from the inner membrane of subsarcolemmal mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytochromes c / metabolism*
  • Dose-Response Relationship, Drug
  • Heart Rate / drug effects
  • In Vitro Techniques
  • Ischemic Preconditioning, Myocardial*
  • Isoflurane / administration & dosage
  • Isoflurane / pharmacology*
  • Male
  • Mitochondria, Heart / enzymology*
  • Mitochondria, Heart / ultrastructure
  • Myocardial Ischemia
  • Myocardial Reperfusion Injury / enzymology*
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardium / pathology
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Ventricular Pressure / drug effects

Substances

  • Cytochromes c
  • Isoflurane