Animal models as the basis of pharmacologic intervention in trauma and sepsis patients.

Abstract

With limited resources and the current concerns about using animals for research purposes, the needs must be clear when setting up trauma and sepsis experiments for pharmacologic interventions. Such interventions are performed typically for four reasons: (1) to study the pathophysiologic role of certain mediators (which can be influenced by pharmacologic agents); (2) to study the therapeutic efficacy of treatment strategies; (3) to study the overall safety of new drugs under trauma/sepsis conditions, which are adjunct studies to standard toxicology; (4) to test new diagnostic procedures in a defined trauma or sepsis setting. Intervention in the inflammatory response may be performed at several levels: (1) at the primary induction site (e.g., by antilipopolysaccharide or by preventing complement activation); (2) at the intermediate mediator level (e.g., by antitumor necrosis factor); (3) at the final mediator level (e.g. , by block of polymorphonuclear neutrophil elastase, and (4) at the target (e.g., by membrane stabilization or enhanced antioxidant defense).