Vascular Response in the Isolated Rat Liver

Abstract

The mechanism underlying the vascular action of endotoxin has been intensively studied with controversial results (1). Evidence has been presented that endotoxin may exert a direct effect on the vessel wall. On the other hand, it m a y act by releasing or potentiating vasoacfive substances, or its peripheral effects may be secondary to alterations in cardiac output and plasma volume. To investigate possible direct vascular actions of endotoxin, the isolated, perfused rat liver offers some unique advantages. A well established technique of perfusion is available and the isolated oxygenated liver maintains its metabolic and histological integrity for a period of 4 to 5 hours. Moreover, this preparation allows for direct, precise measurements of hepatic blood flow, and permits controlled alteration of the perfusing media. By the very nature of the system, endotoxin effects on liver circulation that are secondary to changes in the cardiac output are eliminated. Most important, minor and transient hemodynamic effects of bacterial lipopolysaccharide can be studied at concentrations far below the lethal doses used in the majority of studies in intact animals. Materials and MethodsAnimals.--Adult male Sprague-Dawley rats were used as both blood and liver donors. All animals weighed between 450 and 550 gin and were allowed water and Purina lab chow ad libitum until the time of sacrifice. Donor blood was obtained immediately prior to use in heparinized vacutainer tubes by aortic puncture of etherized rats.Perfusion Technfilue.--The procedure used for the removal and perfusion of a rat liver is essentially that described in detail by Miller (2, 3). The technique involves rapidly removing the liver from an animal and placing it in a system where it is perfused by oxygenated, heparinized blood at 37°C. To insure sterility, all glassware and tubing were autoclaved and assembled in an aseptic manner, and the operative procedure was carried out aseptically on a surgicall~r prepared and draped rat, using sterile equipment. Sterility was monitored throughout the experiments to be described by random culture of the perfusate at various time intervals. Samples plated on blood agar and incubated at 37°C uniformly showed no growth.

Essential Role for Estrogen in Protection against Vibrio vulnificus -Induced Endotoxic Shock

“…This sexually dimorphic response to V. vulnificus endotoxic shock may be due to the differences in hormonal profiles between males and females. It is well established that estrogen produces a variety of effects in females, ranging from mediating ovulation and implantation to regulation of immune function and the cardiovasculature (10,19,22,26,30,31).The effects of estrogen in regulating the responsiveness of females to lipopolysaccharide (LPS)-induced endotoxic shock have not been well studied. In 1965, Nolan and O'Connell (22) described experiments in which female blood altered normal vasoconstrictive responses to endotoxin in isolated rat livers exposed to bacterial LPS.…”

“…In 1965, Nolan and O'Connell (22) described experiments in which female blood altered normal vasoconstrictive responses to endotoxin in isolated rat livers exposed to bacterial LPS. Nolan then followed this with a report in 1967 (21) demonstrating that pretreatment with pharmacological doses of conjugated estrogens for up to 1 h prior to LPS exposure protected rats from the lethal effects of endotoxin.…”

“…This sexually dimorphic response to V. vulnificus endotoxic shock may be due to the differences in hormonal profiles between males and females. It is well established that estrogen produces a variety of effects in females, ranging from mediating ovulation and implantation to regulation of immune function and the cardiovasculature (10,19,22,26,30,31).…”

Effects of Escherichia coli Lipopolysaccharide on Telithromycin Pharmacokinetics in Rats: Inhibition of Metabolism via CYP3A

“…The free fractions (unbound to plasma protein) of telithromycin in plasma were comparable between the two groups of rats. Nolan and O'Connell (21) reported that the hepatic blood flow rate was lower in ECLPS rats.…”

Effect of a bacterial lipopolysaccharide on biliary excretion of a beta-lactam antibiotic, cefoperazone, in rats

“…After the urine and bile flow were stabilized over a 10-min period, the rats received a bolus intravenous injection (within 5 s) of CPZ at a dose of 20 mg/kg. Blood samples of approximately 0.25 ml were collected at designated intervals of 2,5,10,20,30, 45, 60, 75, 90, and 120 min after CPZ administration, and plasma samples were immediately obtained by centrifugation at 6,000 ϫ g for 5 min. Bile samples were collected at three consecutive 10-min periods (0 to 10, 10 to 20, and 20 to 30 min) which were followed by six more consecutive 15-min periods (30 to 45, 45 to 60, 60 to 75, 75 to 90, 90 to 105, and 105 to 120 min).…”