LIVER AS A FOCUS OF IMPAIRED OXYGENATION AND CYTOKINE PRODUCTION IN APORCINE MODEL OF ENDOTOXICOSIS

Objectives: To determine whether the liver is a focus of insufficient oxygenation and whether liver is a source of tumor necrosis factor (TN F) and interleukin-6 (IL-6) in a porcine model of endotoxicosis. Desig n: in vivo, prospective, controlled, repeated measures, experimental s tudy. Setting: Experimental physiology laboratory in a university. Sub jects: Juvenile pigs, weighing 22 to 35 kg. Interventions: Catheters f or blood sampling were inserted into the carotid artery, portal vein, hepatic vein, and pulmonary artery of anesthetized animals. Ultrasonic flow probes were placed on the portal vein and the hepatic artery. Du ring surgery, normal saline was infused intravenously at 25 mL/kg/hr. Following stabilization, animals were allocated randomly to one of two groups. The endotoxemic group (n = 6) received 50 mg/kg of purified E scherichia coli lipopolysaccharide infused into the external jugular v ein over 1 hr. The control group (n = 6) received a sham saline infusi on infused over 1 hr. Once the endotoxin or sham infusion was initiate d, the rate of the intravenous saline infusion was increased to 48 mL/ kg/hr for the remainder of the experiment. Measurements were obtained before the endotoxin or sham infusion, immediately after the infusion, and every 30 mins thereafter for 4 hrs. Measurements and Main Results : Blood gases, lactate, and bioactive TNF and IL 6 concentrations were measured from the carotid artery, portal vein, hepatic vein, and pulm onary artery. The porcine model is characterized by systemic hypotensi on, pulmonary hypertension, and maintenance of cardiac output. Despite decreased hepatic oxygen delivery in endotoxemic animals (p < .02), t here was no change in hepatic oxygen consumption com pared with contro ls. Throughout the experiment, there was net hepatic consumption of la ctate in both groups. There was no significant hepatic production (or consumption) of TNF or IL 6 in either group. Conclusions: In this porc ine model of endotoxicosis, there is a reduction of hepatic oxygen del ivery but dysoxia is not present. The liver is not a source of TNF or IL-6 in this model of endotoxicosis.