Canine models typically develop portal hypertension during shock and bloody diarrhea as a postresuscitation complication that other species do not exhibit. Baboons appear to exhibit a more robust compensatory response to hemorrhagic shock compared with the responses of humans and most other species, and are able to tolerate a mean arterial blood pressure of 40 mm Hg for over 8 hours before they exhibit signs of decompensation.

Models of hemorrhagic shock are of two basic types: controlled and uncontrolled with respect to the manner in which ongoing blood loss is allowed to proceed. Controlled models are either of the fixed-volume or constant-pressure varieties and are generally more reproducible than uncontrolled bleeding models, which usually involve laceration, puncture, or transection. When an experimental hypothesis includes the treatment effect on homeostasis, uncontrolled bleeding models are relevant. Since shock is a dynamic process involving dramatic changes in cardiovascular and metabolic states that vary with time, species, laboratory, and even investigator, it is important to evaluate the effectiveness of various resuscitative regimens not simply on the basis of time but also on the basis of a more complete definition of the stage of physiologic compensation at the time that treatment is initiated. It has been shown that the type of anesthesia, state of hydration, nutrition status, core temperature, and use of heparin all affect the time course and degree of compensatory capacity of the animal in response to blood loss.

Effects of Extent of Hypotension and Rates of Hemorrhage on Immune Function in Mouse Models

Available information indicates that even transient hypotension in the absence of significant tissue trauma is sufficient to produce marked suppression of both specific and nonspecific immune responses. This appears to be the case irrespective of whether the model of hemorrhage used is one of a fixed-pressure versus a fixed-volume bleed, a bleedout over a relatively brief period (less than 5 minutes of cardiac stick/fixed-volume model), an intermediate period (approximately 5 to 15 minutes of hemorrhage to fixed pressure), or a protracted period (tail vein laceration or uncontrolled hemorrhage models), as well as whether the animal is anesthetized or unanesthetized. Also, although many of these models are typically nonlethal, they render the animal highly susceptible to subsequent lethal septic challenge. This appears to be the case irrespective of the administration of standard fluid resuscitation (with or without blood), although it can be modified by the rate of fluid administration and by the nature of the resuscitation fluid (e.g., lactated Ringer's solution versus hypertonic saline).

Nonetheless, trauma appears to provide a modulatory effect in the sense that it can be additive or prolongs the duration of immune aberrations encountered in these models. Another significant modifier frequently present in many models is an anticoagulant, such as heparin. Studies indicate that this agent can reduce the severity of insult produced in these models. Interestingly, microbial



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