Valproic acid reversed pathologic endothelial cell gene expression profile associated with ischemia-reperfusion injury in a swine hemorrhagic shock model

The functional pathways associated with vascular ischemia-reperfusion are not fully understood. This study found that valproic acid (VPA), administered along with the application of a supraceliac cross-clamp, improved clinical, physiologic, and histologic changes in a swine model of hemorrhage and ischemia-reperfusion: 35% blood volume hemorrhage, 50-minute supraceliac aortic cross-clamp, and a 6-hour resuscitation. A functional analysis of endothelial dysfunction, with relative quantitative polymerase chain reaction validation, demonstrated the initial changes in endothelial cell dysfunction occurred through vascular endothelial growth factor and transforming growth factor-β gene members. This study demonstrates that pharmaceutical agents administered with an ischemic injury are beneficial after ischemia and target two common functional endothelial pathways.