Surgery
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DNA transcription is regulated in part by acetylation of nuclear histones, controlled by 2 groups of enzymes: histone deacetylases (HDAC) and histone acetyl transferases (HAT). We have shown previously that hemorrhage and resuscitation are associated with HDAC/HAT imbalance, which influences the acetylation status of cardiac histones. The goals of this study were to determine whether: (1) resuscitation after hemorrhage affects histone acetylation in a fluid- and organ-specific fashion; and (2) administration of HDAC inhibitors influences histone acetylation and subsequent gene expression. ⋯ Resuscitation with various fluids, as well as infusion of pharmacologic HDAC inhibitors affects histone acetylation in a fluid- and organ-specific fashion, even when administered post-insult for a limited period of time. Uniquely affected genes are associated with metabolism, cellular growth, proliferation, differentiation, transformation, and cellular signaling.