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

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.

• Authors: Qian Li, Chunwei Lian, Ronghua Zhou, Tao Li, Xujin Xiang, Bin Liu
• Journal: Heart, lung & circulation (Heart Lung Circ) Vol. 22 Issue 4 Pg. 276-83 (Apr 2013) ISSN: 1444-2892 [Electronic] Australia
• PMID: 23261327 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Chemical References

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

Topics

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