Ascorbate prevents microvascular dysfunction in the skeletal muscle of theseptic rat

Septic patients have low plasma ascorbate concentrations and compromised mi crovascular perfusion. The purpose of the present experiments was to determ ine whether ascorbate improves capillary function in volume-resuscitated se psis. Cecal ligation and perforation (CLP) was performed on male Sprague-Da wley rats. The concentration of ascorbate in plasma and urine, mean arteria l blood pressure, and density of continuously perfused capillaries in the e xtensor digitorum longus muscle were measured 24 h after surgery. CLP cause d a 50% decrease (from 56 +/- 4 to 29 +/- 2 muM) in plasma ascorbate concen tration, 1,000% increase (from 46 +/- 13 to 450 +/- 93 muM) in urine ascorb ate concentration, 20% decrease (from 115 +/- 2 to 91 +/- 2 mmHg) in mean a rterial pressure, and 30% decrease (from 24 +/- 1 to 17 +/- 1 capillaries/m m) in the density of perfused capillaries, compared with time-matched contr ols. A bolus of intravenous ascorbate (7.6 mg/100 g body wt) administered i mmediately after the CLP procedure increased plasma ascorbate concentration and restored both blood pressure and density of perfused capillaries to co ntrol levels. In vitro experiments showed that ascorbate (100 muM) inhibite d replication of bacteria and prevented hydrogen peroxide injury to culture d 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 stu dy supports the view that ascorbate may be beneficial for patients with sep tic syndrome.