Journal of Applied Physiology AJP: Lung Cellular and Molecular Physiology
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J Appl Physiol 90: 795-803, 2001;
8750-7587/01 $5.00
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Vol. 90, Issue 3, 795-803, March 2001

Ascorbate prevents microvascular dysfunction in the skeletal muscle of the septic rat

John Armour1,3, Karel Tyml2,3, Darcy Lidington2,3, and John X. Wilson1

Departments of 1 Physiology and 2 Medical Biophysics, University of Western Ontario, and 3 A. C. Burton Vascular Biology Laboratory, Lawson Health Research Institute, London, Ontario, Canada N6A 5C1

Septic patients have low plasma ascorbate concentrations and compromised microvascular perfusion. The purpose of the present experiments was to determine whether ascorbate improves capillary function in volume-resuscitated sepsis. Cecal ligation and perforation (CLP) was performed on male Sprague-Dawley rats. The concentration of ascorbate in plasma and urine, mean arterial blood pressure, and density of continuously perfused capillaries in the extensor digitorum longus muscle were measured 24 h after surgery. CLP caused a 50% decrease (from 56 ± 4 to 29 ± 2 µM) in plasma ascorbate concentration, 1,000% increase (from 46 ± 13 to 450 ± 93 µM) in urine ascorbate concentration, 20% decrease (from 115 ± 2 to 91 ± 2 mmHg) in mean arterial pressure, and 30% decrease (from 24 ± 1 to 17 ± 1 capillaries/mm) in the density of perfused capillaries, compared with time-matched controls. A bolus of intravenous ascorbate (7.6 mg/100 g body wt) administered immediately after the CLP procedure increased plasma ascorbate concentration and restored both blood pressure and density of perfused capillaries to control levels. In vitro experiments showed that ascorbate (100 µM) inhibited replication of bacteria and prevented hydrogen peroxide injury to cultured microvascular endothelial cells. These results indicate that ascorbate is lost in the urine during sepsis and that a bolus of ascorbate can prevent microvascular dysfunction in the skeletal muscle of septic animals. Our study supports the view that ascorbate may be beneficial for patients with septic syndrome.

vitamin C; blood pressure; antioxidant; capillary; septicemia


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