Pharmacologic agents in the treatment of ischemia, hemorrhagic shock, and sepsis

Academic Article

Abstract

  • The systemic inflammatory response to perfusion deficits, injury, and sepsis is characterized by a myriad of physiologic changes that appear to be mediated by numerous factors. It is not possible to implicate a single factor that is responsible for the pathologic process that leads to multiple organ failure. However, it is apparent that interruption of the systemic-inflammatory cascade at various points can attenuate and, in certain instances, ablate the damage to cells and organs and improve survival. At present, traditional therapy is directed at the effects of this pathologic process. The agents reviewed in this article have the potential to ameliorate or prevent cellular and organ dysfunction. Since many of the mediators have recognizable beneficial effects, the major challenge to any therapeutic intervention will be to allow the continuation of normal inflammation, which is critical for host defense, while limiting the pathologic process, which causes cellular and organ injury. With our increasing knowledge of molecular biology and cellular function in various organs during and following injury, the more directive and specific the therapy. One can envision multimodality therapy that will upregulate certain processes while others are attenuated. At present, clinical trials of ATP-MgCl2, pentoxifylline, calcium channel blockers, chloroquine, and nutritional immunomodulation seem indicated. Since tumor necrosis factor, interleukin-1, and interleukin-6 seem to be early mediators of this response, well-controlled and designed studies that modify their action should be undertaken in multi-institutional settings. In this regard, preliminary trials using antibodies to tumor necrosis factor and interleukin-1 receptor antagonists are ongoing. © 1992.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Author List

  • Harkema JM; Singh G; Wang P; Chaudry IH
  • Start Page

  • 189
  • End Page

  • 216
  • Volume

  • 7
  • Issue

  • 3