Reduction of cardiac cell death after helium postconditioning in rats: transcriptional analysis of cell death and survival pathways.

ABSTRACT

Helium, a noble gas, has been used safely in humans. In animal models of regional myocardial ischemia/reperfusion (I/R) it was shown that helium conditioning reduces infarct size. Currently, it is not known how helium exerts its cytoprotective effects and which cell death/survival pathways are affected. The objective of this study, therefore, was to investigate the cell protective effects of helium postconditioning by PCR array analysis of genes involved in necrosis, apoptosis and autophagy. Male rats were subjected to 25 min of ischemia and 5, 15 or 30 min of reperfusion. Semiquantitative histological analysis revealed that 15 min of helium postconditioning reduced the extent of I/R-induced cell damage. This effect was not observed after 5 and 30 min of helium postconditioning. Analysis of the differential expression of genes showed that 15 min of helium postconditioning mainly caused upregulation of genes involved in autophagy and inhibition of apoptosis versus I/R alone. The results suggest that the cytoprotective effects of helium inhalation may be caused by a switch from pro-cell-death signaling to activation of cell survival mechanisms, which appears to affect a wide range of pathways.