Age-associated differences in gene expression in response to delayed anesthetic preconditioning

Evidence suggests that the protective benefits of anesthetic preconditioning (APC) are significantly attenuated in the aged myocardium. In this study, we investigated the effect of aging on gene expression in delayed APC. Hearts from Fischer 344 rats, age 4 or 24 months, were divided into five groups: control; ischemia/reperfusion (I/R); and delayed APC at 6, 12, and 24 h. Whole-genome array was studied using Affymetrix Rat Genome 230 2.0 array. Data were analyzed for significant ≥2.0-fold changes in gene expression. Microarray results were confirmed by quantitative real-time reverse transcription-polymerase chain reaction. Of the 28,000 genes represented on the Affymetrix Rat Genome 230 2.0 Microarray chip, 24 transcripts in 6 h APC, 28 in 12 h APC, and 28 in 24 h APC group displayed significant up-regulation in mRNA levels, and 70 transcripts in 6 h APC, 101 in 12 h APC, and 82 in 24 h APC displayed significant down-regulation in young rat hearts. These altered genes fall into functional categories of cell defense/death, cell structure, gene expression/protein synthesis, inflammatory response/growth/remodeling, and signaling/communication. Although alterations for some genes were in common, the numbers of changed genes in old rats were markedly and consistently lower than the young rats. Twenty-four hour delayed APC also significantly reduced infarct size and improved myocardial left ventricular function in young hearts, effects that were not observed in old rat hearts. We concluded that delayed APC profoundly and differentially affected gene expression profiles of the cardiomyocyte in an age-associated pattern. The impaired genomic response to delayed APC could underlie the loss of the protective benefits of preconditioning in aged hearts.