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.
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.
Lucchinetti
E
E
Institute of Anesthesiology, University Hospital Zurich, Switzerland.
da Silva
R
R
Pasch
T
T
Schaub
M C
MC
Zaugg
M
M
D000777:Anesthetics; D000818:Animals; D020869:Gene Expression Profiling; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D020411:Oligonucleotide Array Sequence Analysis; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000777:Anesthetics; D007530:Isoflurane