Microarray analyses of genes regulated by isoflurane anesthesia in vivo: a novel approach to identifying potential preconditioning mechanisms.

BACKGROUND

Although general anesthetics are recognized for their potential to render patients unconscious during surgery, exposure can also lead to long-term outcomes of both cellular damage and protection. As regards the latter, delayed anesthetic preconditioning is an evolutionarily conserved physiological response that has the potential for protecting against ischemic injury in a number of tissues. Although it is known that delayed preconditioning requires de novo protein synthesis, knowledge of anesthetic-regulated genes is incomplete. In this study, we used the conserved nature of preconditioning to analyze differentially regulated genes in 3 different rat tissues. We hypothesized that by selecting those genes regulated in multiple tissues, we could develop a focused list of gene candidates potentially involved in delayed anesthetic preconditioning.

METHODS

Young adult male Sprague-Dawley rats were anesthetized with a 2% isoflurane/98% air mixture for 90 minutes. Immediately after anesthetic exposure, animals were euthanized and liver, kidney, and heart were removed and total RNA was isolated. Differential gene expression was determined using rat oligonucleotide gene arrays. Array data were analyzed to select for genes that were significantly regulated in multiple tissues.

RESULTS

All 3 tissues showed differentially regulated genes in response to a clinically relevant exposure to isoflurane. Analysis of coordinately regulated genes yielded a focused list of 34 potential gene candidates with a range of ontologies including regulation of inflammation, modulation of apoptosis, regulation of ion gradients, and maintenance of energy pathways.

CONCLUSIONS

Through using an analysis approach focusing on coordinately regulated genes, we were able to generate a focused list of interesting gene candidates with potential to enable future preconditioning studies.