Cell swelling and depolarization in hemorrhagic shock

Although an increase in intracellular water volume (IWV) in hemorrhagic shock has been inferred from measured changes in transmembrane potential, it has not been measured directly. We have described the presence of a circulating protein that appears in hemorrhagic shock [circulating shock protein (CSP) 70] that depolarizes numerous cell types. To determine if this substance produced a concurrent increase in intracellular water, cells were incubated with CSP 70. Then we measured IWV as the difference between the 3H water space and the [14C]mannitol space. CSP 70 increased IWV 9% in rat red blood cells (RBCs) (n = 8, p < 0.05), 22% in rat H9c2 cells (n = 7, p < 0.05), 11% in dog RBCs (n = 10, p < 0.005), and 31% in dog white blood cells (n = 8, p < 0.005). The results indicate that a protein that circulates in hemorrhagic shock depolarizes cells and increases intracellular water. This suggests that the changes in transmembrane potential observed in hemorrhagic shock are accompanied by movement of extracellular fluid into cells and may account for the inability to restore blood volume after large hemorrhage.