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Seminars in Cardiothoracic and Vascular Anesthesia
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Novel Insights Into the Pathogenesis and Therapy of Circulatory Shock

Jay S. Steingrub

Baystate Medical Center, Department of Medicine and Surgery, Division of Critical Care Medicine, Springfield, MA

Several lines of evidence suggest central roles for nitric oxide, oxygen free radicals, cytokines, and adhesion molecules in circulatory shock. Lipid peroxidation fre quently accompanies ischemia-reperfusion injury; re cruitment of leukocytes exposed to ischemia-reperfu sion injury is largely dependent on leukocytes and endothelial cell adhesion interaction, enhanced nitric oxide stimulation by proinflammatory cytokines contrib utes to increased gut mucosal permeability in sepsis, and tumor necrosis factor (TNF) administration mimics the hemodynamic changes characteristic of circulatory shock. Recent advances in molecular and cellular biol ogy have paved the way for innovative approaches to the treatment of circulatory shock. Novel pharmaco logic approaches are being directed at three distinct levels of the inflammatory cascade: the inciting insult (ie, endotoxin), the mediators (ie, TNF, interleukin-1, oxygen free radicals), and the effector cells (ie, neutro phils). The intent of this review is to discuss the biology of mediators in circulatory shock as well as the experi mental and clinical evidence implicating their role in development and pathogenesis of the injury. Current status of novel adjunctive therapies for circulatory shock is reviewed.

Seminars in Cardiothoracic and Vascular Anesthesia, Vol. 2, No. 1, 31-45 (1998)
DOI: 10.1177/108925329800200103
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