Search

The administration of small dosages of endotoxin to sheep results in cardiopulmonary changes characterized by an elevation in pulmonary lymph flow, vascular resistance, and hemoconcentration, and a reduction in cardiac output. These changes are not as great when the narcotic antagonist, naloxone (2 mg/kg/h for 5 h), is infused prior to and during the endotoxin response. The present study evaluates the ovine response to endotoxin when naloxone is administered 1 h after the endotoxin infusion. Sheep were prepared by implanting cardiopulmonary and lung lymphatic catheters. One week following the last surgical procedure, the sheep, in the awake state, were given 0.75 micrograms/kg of endotoxin and the variables were measured. Three days later, a second dose of endotoxin was administered and variables were again measured. An infusion of naloxone was given with one of the dosages of lipopolysaccharide. Two dosages of the narcotic antagonist were used. One group received 2 mg/kg bolus + 2 mg/kg/h for 5 h; another group was given twice this amount. Both dosages were started 1 h after endotoxin. The response to endotoxin was essentially the same whether or not the sheep were treated with naloxone. If naloxone pretreatment is effective and posttreatment is not, then it is possible that an opiatelike substance might be released by endotoxin which in turn results in the ultimate release of the lesion-producing substance.

The involvement of endorphins in the ovine cardiopulmonary response to endotoxin was evaluated by measuring blood levels of opiate receptor binding substances and administering the opiate receptor blocking agent naloxone prior to and after the administration of lipopolysaccharide. The animals were prepared for chronic study by placement of cardiovascular catheters and cannulation of the lung lymphatic at least 1 wk prior to study. The sheep were given endotoxin (0.75 micrograms/kg) and studied for 6 h. This was accomplished twice in the same animal. Naloxone (2 mg/kg bolus + 2 mg X kg-1 X h-1) was given with one of the two doses of the lipopolysaccharide. The response to endotoxin could be divided into two phases. In phase 1, there was an increase in protein-poor lung lymph and a marked increase in pulmonary artery pressure. In phase 2, the pulmonary lymph flow was elevated but the lymph protein level was higher than in phase 1. The pulmonary artery pressure, however, was near normal. During both phases leukocytes and cardiac output were reduced and the hematocrit was elevated. There was an increase in opiatelike materials in the plasma of these animals, and the response to endotoxin was partially blocked by naloxone. This suggested that endorphin-like materials were involved in the response to endotoxin.