title: Abnormal tissue oxygenation and cardiovascular changes in endotoxemia.
abstract: 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.
authors.affiliation: Unit of Critical Care, and Physiological Flow Studies Group, Imperial College of Science, Technology and Medicine, London, United Kingdom.
authors.forename: P B
authors.initials: PB
authors.lastname: Anning
authors.forename: M
authors.initials: M
authors.lastname: Sair
authors.forename: C P
authors.initials: CP
authors.lastname: Winlove
authors.forename: T W
authors.initials: TW
authors.lastname: Evans
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000503:physiopathology*; D019446:Endotoxemia / Q000503:physiopathology* / Q000628:therapy; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005440:Fluid Therapy; D006439:Hemodynamics / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology*; D010313:Partial Pressure; D011659:Pulmonary Gas Exchange / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012151:Resuscitation
chemical_list: D004791:Enzyme Inhibitors; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester