Pretreatment with xenon protected immature rabbit heart from ischaemia/reperfusion injury by opening of the mitoKATP channel

Heart Lung Circ. 2013 Apr;22(4):276-83. doi: 10.1016/j.hlc.2012.10.016. Epub 2012 Dec 21.

Abstract

Background: The noble gas anaesthetic, xenon has previously been shown to protect the adult myocardium from ischaemia/reperfusion (I/R) injury, however its effect on immature myocardium is unclear. The aim of this study was to investigate the effect of xenon on the isolated immature heart.

Methods: Isolated, immature (2-3weeks old) New Zealand rabbit hearts were perfused with Krebs-Henseleit buffer via Langendorff-mode. After 20min of baseline equilibration, hearts were pretreated with 75% xenon, 75% xenon+100μM diazoxide, or 75% xenon+100μM 5-hydroxydecanoate, and then subjected to 1h of global ischaemia and 3h of reperfusion.

Results: Pretreatment with 75% xenon significantly improved cardiac function (P<0.01 vs. the I/R group, respectively), limited myocardial infarct size (20.83±2.16%, P<0.01 vs. 35.82±2.14% of the I/R group), reduced cardiac enzyme release (CK-MB, 1.00±0.19IU/L, P<0.01 vs. 0.44±0.14IU/L of the I/R group; LDH, 6.15±1.06IU/L P<0.01 vs. 3.49±0.37IU/L of the I/R group) and decreased apoptosis (6.17±0.56%, P<0.01 vs. 11.31±0.93% of the I/R group). In addition, the mitochondrial structure changes caused by I/R injury were largely prevented by 75% xenon pretreatment (1.37±0.16, P<0.01 vs. 2.32±0.13 of the I/R group). The mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channel opener diazoxide did not influence the effect of xenon, but the specific mitoKATP channel blocker 5-hydroxydecanoate completely abolished this effect.

Conclusions: Our study demonstrated that pretreatment with 75% xenon protected immature heart from I/R injury, and this protection was probably mediated by preservation of myocardial mitochondria and opening of mitoKATP channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Inhalation / pharmacology*
  • Animals
  • Anti-Arrhythmia Agents / adverse effects
  • Anti-Arrhythmia Agents / pharmacology
  • Decanoic Acids / adverse effects
  • Decanoic Acids / pharmacology
  • Hydroxy Acids / adverse effects
  • Hydroxy Acids / pharmacology
  • Male
  • Mitochondria, Heart / metabolism*
  • Muscle Proteins / antagonists & inhibitors
  • Muscle Proteins / metabolism*
  • Myocardial Reperfusion Injury* / metabolism
  • Myocardial Reperfusion Injury* / pathology
  • Myocardial Reperfusion Injury* / physiopathology
  • Myocardial Reperfusion Injury* / prevention & control
  • Myocardium / metabolism*
  • Potassium Channels / metabolism*
  • Rabbits
  • Xenon / pharmacology*

Substances

  • Anesthetics, Inhalation
  • Anti-Arrhythmia Agents
  • Decanoic Acids
  • Hydroxy Acids
  • Muscle Proteins
  • Potassium Channels
  • mitochondrial K(ATP) channel
  • Xenon
  • 5-hydroxydecanoic acid