Background and methods: The administration of endotoxin in small dosages to sheep results in an acute decrease followed by an increase in cardiac output. It has previously been determined that the initial decrease in output was the result of a reduction in blood flow to the mesenteric areas. These changes were associated with increased blood concentrations of beta endorphin. The present study was accomplished to determine if the systemic cardiovascular response to endotoxin could be affected by the administration of an opiate receptor-blocking agent. Female range sheep (n = 12) were prepared for chronic study by implantation of cardiopulmonary catheters and a flow probe on the cephalic mesenteric artery. Endotoxin (Escherichia coli, 1 microgram/kg) was administered to these animals. Half of the sheep were treated with naloxone (2 mg/kg + 2 mg/kg.hr), and the remainder with an equivalent volume of sodium chloride (0.9%).
Results: In untreated sheep, cardiac indices decreased by 15% to 20% (5.1 +/- 0.1 to 4.2 +/- 0.4 L/min.m2) between 0 and 1 hr and 2 and 5 hrs after endotoxin (4.5 +/- 0.2 L/min.m2), and then increased to a value 40% (7.2 +/- 0.6 L/min.m2) above baseline by 12 hrs. Flow in the cephalic mesenteric artery decreased in a pattern similar to the reduction in cardiac index (962 +/- 152 [time, T = 0] to 379 +/- 111 [T = 0.8] and 384 +/- 88 mL/min [T = 4.0], p less than .05) but did not increase to the same extent (1008 +/- 153 mL/min [T = 4.0], p greater than .05). There was a concomitant increase in the plasma beta-endorphin concentrations as the blood flow decreased (5 +/- 4 [T = 0] to 40 +/- 15 pg/mL [T = 0.8; untreated group], p less than .05; and 10 +/- 4 to 50 +/- 7 pg/mL [T = 0.8; naloxone-treated group], p less than .05). In the naloxone-treated group, the same pattern of cardiac output change was noted with endotoxin; however, reduction of mesenteric artery flow was only 30% (1118 +/- 129 to 908 +/- 122 mL/min, p less than .05) of the value seen in the untreated animals (962 +/- 152 to 379 +/- 111 mL/min, p less than .05). These changes in mesenteric blood flow were statistically significant from one another. As the cardiac output increased in the sheep treated with the opiate antagonist, mesenteric blood flows increased 20% above the baseline value (1391 +/- 199 mL/min, p less than .05).
Conclusions: The decrease in cardiac output noted with endotoxin can be accounted for by the decrease in the blood flow in the cephalic mesenteric artery. This phenomenon can be attributed, at least in part, to the release of endorphins. There is both a vasodilation and constriction during endotoxemia in the ovine model.