ANIMAL-MODELS AS THE BASIS OF PHARMACOLOGICAL INTERVENTION IN TRAUMA AND SEPSIS PATIENTS

With limited resources and the current concerns about using animals fo r research purposes, the needs must be clear when setting up trauma an d sepsis experiments for pharmacologic interventions. Such interventio ns are performed typically for four reasons: (1) to study the pathophy siologic role of certain mediators which can be influeuced by pharmaco logic agents); (2) to study the therapeutic efficacy of treatment stra tegies; (3) to study the overall safety of new drugs under trauma/seps is conditions, which are adjunct studies to standard toxicology; (4) t o test new diagnostic procedures in a defined trauma or sepsis setting . Intervention in the inflammatory response may be performed at severa l levels: (1) at the primary induction site (e.g., by antilipopolysacc haride or by preventing complement activation); (2) at the intermediat e mediator level (e.g., by antitumor necrosis factor); (3) at the fina l mediator level (e.g., by block of polymorphonuclear neutrophil elast ase, and (4) at the target (e.g., by membrane stabilization or enhance d antioxidant defense).