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 (
PtO2) and its response to changes in fraction of inspired
oxygen (FIO2) in rats rendered endotoxemic. Simultaneous measurements were made of systemic hemodynamic indices and arterial blood gas tensions. At normal PaO2,
PtO2 in endotoxemic animals was significantly lower than in control animals, with marked attenuation of the response to increasing FIO2. These changes were associated with significant metabolic acidemia. In volume-resuscitated endotoxemic rats,
PtO2 and blood pH were unchanged. A significant reduction in the
PtO2 response to
hyperoxia was observed in animals treated with the NOS inhibitor
NG-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
PtO2, whereas
nitric oxide synthase (NOS) inhibition has deleterious effects on muscle
PtO2 in both control and endotoxemic animals.