are reinfused with the shed blood or various resuscitation fluids, and survival as well as physiologic measurements can be monitored at intervals to determine responses and rates of survival versus death. A number of criticisms have indicated the shortcomings of this model. These shortcomings stem from such things as pretreatment with agents that interfere with the sympathetic nervous system (e.g., ganglionic blockers or adrenergic antagonists) or the use of potent general anesthetics that decrease the level of the shed blood volume at which the desired mean arterial pressure is reached and that lower the catecholamine and hormonal responses, indicating a lower level of hemorrhagic stress. In other words, the mechanics of the experimental design may influence the endpoints of research that uses this model.

When a controlled hemorrhage by percentage of blood volume or body weight is used, the indicators of the response rather than the shed blood volume are the blood pressure and other hemodynamic measurements as well as other measurements of stress, as indicated above. The animals are held for a period of time and are then reinfused with shed blood or the fluid resuscitation being tested, or a combination of both. This technique also permits measurements of various response parameters and can be used to obtain survival data. The common criticism of both of these controlled hemorrhage models is that they do not mimic actual shock conditions in humans.

The uncontrolled hemorrhage model can be totally uncontrolled hemorrhage from either a catheter or a rent in the aorta or major vessel. In this model, controlled rates of bleeding are sometimes used or controlled rates of bleeding are combined with a partially controlled bleeding model with further hemorrhage being uncontrolled. Various hemodynamic measurements as well as other organ function measurements can be made as described above for the controlled hemorrhage model. It has been stated that the model that most closely approximates battlefield casualty conditions is one that uses the uncontrolled hemorrhage in the absence of anesthesia in subjects who were previously dehydrated and exposed to various stresses. Although this might be a closer approximation to battlefield conditions, the ability to measure responses and outcomes would appear to be better with controlled hemorrhage models, simply because additional experimental variability is introduced by uncontrolled hemorrhage.

The combat injury is usually a combination of hemorrhage and soft-tissue injury. The soft-tissue injury component is most often a penetrating injury that produces a number of subsequent reactions that can influence the outcome in different ways. The release of cytokines and other substances from injured tissue contributes significantly to the organ function disorders associated with shock. The animal model that most closely approximates the battlefield injury should include not only an acute hemorrhage but also some aspects of tissue injury such as a penetrating or crush injury to an extremity. Penetrating injury of visceral organs may introduce other complicating factors such as septic shock introduced by penetrating injuries of the gut and other abdominal visceral organs. Penetrating wounds of the chest may add additional injuries to the heart or lungs,