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BJA Advance Access first published online on June 6, 2005
This version published online on June 14, 2005

British Journal of Anaesthesia, doi:10.1093/bja/aei155
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© The Board of Management and Trustees of the British Journal of Anaesthesia 2005. All rights reserved. For Permissions, please e-mail: journal.permissions@oupjournals.org
Accepted April 1, 2005

Laboratory Investigation

Anaesthetic preconditioning but not postconditioning prevents early activation of the deleterious cardiac remodelling programme: evidence of opposing genomic responses in cardioprotection by pre- and postconditioning

E. Lucchinetti 1, R. da Silva 1, T. Pasch 2, M. C. Schaub 3, and M. Zaugg 1*

1 Institute of Anesthesiology, University Hospital Zurich, Switzerland; Institute of Pharmacology and Toxicology, University of Zurich, Switzerland
2 Institute of Anesthesiology, University Hospital Zurich, Switzerland
3 Institute of Pharmacology and Toxicology, University of Zurich, Switzerland

* To whom correspondence should be addressed.
M. Zaugg, E-mail: michael.zaugg{at}usz.ch


   Abstract

Background. Anaesthetic preconditioning (A_PreC) and postconditioning (A_PostC) both provide protection against ischaemia-reperfusion in the heart. However, post-ischaemic gene responses may differ between the two therapeutic strategies.

Methods. Isolated perfused rat hearts were exposed to 40 min test ischaemia followed by 3 h reperfusion and used to determine transcriptional changes in response to A_PreC and A_PostC. A_PreC was induced by 15 min of isoflurane 2.1 vol% followed by 10 min of washout, and A_PostC was induced by 15 min of isoflurane 2.1 vol% administered at the onset of reperfusion. Untreated hearts served as ischaemic control (ISCH). Coupled-two way clustering (CTWC) and principal component analysis (PCA) were used to identify gene expression patterns.

Results. A_PreC (7[SD 1]%) and A_PostC (6[2]%) produced a similar decrease in infarct size (ISCH 36[1]%, P<0.05). However, post-ischaemic genomic reprogramming was completely different. Few genes were jointly regulated (2.1{per thousand} of upregulated genes and 1.3% of downregulated genes). Eight stable gene clusters including three subclusters emerged from CTWC and were related to inflammation, signalling, ion channels, transcription factors, long interspersed repetitive DNA, heat shock response and remodelling. Two stable sample clusters were identified for postconditioned hearts (first cluster) and for all other protocols (second cluster), emphasizing the unique cardiac phenotype elicited by A_PostC. PCA revealed a close genomic relationship between A_PreC and non-ischaemic healthy myocardium.

Conclusions. A_PreC, but not A_PostC, induces a post-ischaemic gene expression profile similar to virgin myocardium and prevents activation of the deleterious cardiac remodelling programme. Hence A_PreC and A_PostC are not interchangeable with respect to their molecular outcome in the heart.

Keywords: anaesthetics volatile, isoflurane; genetic factors; heart, ischaemia; model, rat.

Declaration of interest. M. Zaugg received 25 000 CHF from Abbott Switzerland for this project.

This is a new version of this article as there was an error in the xml tagging that resulted in the last author's name being cited incorrectly in PubMed.


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