Am. J. Respir. Crit. Care Med., Volume 159, Number 6, June 1999, 1710-1715

Abnormal Tissue Oxygenation and Cardiovascular Changes in Endotoxemia

PETER B. ANNING, MARK SAIR, C. PETER WINLOVE, and TIMOTHY W. EVANS

Unit of Critical Care, and Physiological Flow Studies Group, Imperial College of Science, Technology and Medicine, London, United Kingdom

Experimental sepsis induces disturbances in microcirculatory flow and nutrient exchange that may result in impaired tissue oxygenation. Volume resuscitation is a principal clinical intervention in patients with sepsis. Nitric oxide (NO) has been implicated in the pathophysiology of endotoxemia, but few data exist concerning the effects of either NO synthase inhibition (NOSi) or volume resuscitation on microvascular regulation and tissue oxygenation. Amperometric measurements were made of skeletal muscle (tissue) oxygen tension (Pt_O2) and its response to changes in fraction of inspired oxygen (FI_O2) in rats rendered endotoxemic. Simultaneous measurements were made of systemic hemodynamic indices and arterial blood gas tensions. At normal Pa_O2, Pt_O2 in endotoxemic animals was significantly lower than in control animals, with marked attenuation of the response to increasing FI_O2. These changes were associated with significant metabolic acidemia. In volume-resuscitated endotoxemic rats, Pt_O2 and blood pH were unchanged. A significant reduction in the Pt_O2 response to hyperoxia was observed in animals treated with the NOS inhibitor N^G-nitro-L-arginine methyl ester (L-NAME), an effect not reversed by fluid resuscitation. These data suggest that significant tissue hypoxia and abnormal microvascular control occur in endotoxemia. Volume resuscitation can reverse the changes in Pt_O2, whereas nitric oxide synthase (NOS) inhibition has deleterious effects on muscle Pt_O2 in both control and endotoxemic animals.

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