Previous studies have shown that administering
trans-sodium crocetinate (
TSC) as a treatment of
hemorrhagic shock leads to increased whole-body oxygen consumption and survival as well as protection of the liver and kidney. It has been suggested that
TSC increases
oxygen delivery by increasing the diffusivity of
oxygen through plasma. However, as with any novel mechanism of action, there are always questions about whether the results could also be ascribed to other, previously described mechanisms of action. This study was designed to look at some aspects of that by examining the effect of different
TSC dosing regimens on the blood pressure and the production of
cytokines after
hemorrhage because both responses have been reported with compounds that act via other mechanisms. In a constant-pressure rat model of
hemorrhagic shock, it was seen that a singe bolus injection of
TSC results in an immediate but transient increase in the arterial blood pressure. This is similar to the effect reported previously for using 100%
oxygen. It was also found that if the
TSC injections were repeated periodically over an hour, a sustained increase in the blood pressure would occur. Because inflammatory
cytokines have been implicated in mortality and tissue damage, it has been suggested that
TSC may affect the production of
cytokines. Thus, the effect of
TSC on the production of
TNF-alpha and
IL-10 was also examined. The data show that treatment with
TSC results in lower concentrations of
TNF-alpha in the liver and spleen as well as lower concentrations of
IL-10 in the spleen. Again, similar effects on other
cytokines have been seen with 100%
oxygen. These results support the hypothesis that the effects of
TSC on
hemorrhagic shock are mediated via an effect on
oxygen.