Trans sodium crocetinate for hemorrhagic shock: effect of time delay in initiating therapy

A new drug, trans sodium crocetinate (TSC), has been suggested for use in resuscitation after trauma. TSC has been shown to increase survival in a rat model of hemorrhagic shock. It also results in an increase in blood pressure and a decrease in plasma lactate levels when given immediately after hemorrhage. TSC increases whole-body oxygen consumption rates, and it is thought that its physiological effects are due to the increased oxygen availability. In fact, TSC therapy and 100% oxygen therapy show similar results when used in the same rat hemorrhage model. It has been suggested, however, that 100% oxygen therapy is effective only if begun immediately after hemorrhage. Such a window of opportunity has been said to exist for other resuscitation methods; thus, the current study is to determine if this is true for TSC. In one series of experiments, rats were bled 60% of their blood volumes and given an injection of TSC (or saline) 20 min after the hemorrhage ended. The injection was then repeated four times, spaced 10 min apart. Thirty minutes after the final injection, the animals were infused with normal saline. TSC again restored blood pressure and other parameters, but repeated dosing was necessary. In addition, this therapy prevented an increase in liver enzymes (transaminases) as measured 24 h after hemorrhage. In a second study, rats were bled 60% of their blood volumes, followed by a second bleeding (an additional 10%) done 10 min later. No subsequent fluid was infused in this group. The majority of the animals treated with TSC after the second hemorrhage survived, whereas the controls did not. These data suggest that TSC is effective when given after a delay. The dosing regimen must be different, however, presumably because of the blood acidosis that develops after hemorrhage. The results also suggest that TSC may be protective against secondary liver damage resulting from trauma.