Influence of prostanoids on gastrointestinal mucosal injury in experimental septic shock

Capillary stasis and mucosal injury in the stomach and small intestine were studied in septic shocked pigs. Septicemia was induced by live E. coli i.v. in 28 animals. Additionally, five animals were infused with Ringer's solution and served as sham controls. The 28 E. coli-infused animals were pretreated with either a cyclooxygenase inhibitor--indomethacin, n = 6, a thromboxane (TxA2)-synthetase inhibitor--UK 38,485 alone, n = 6, or combined with a serotonin-antagonist--ketanserin, n = 9. Seven E. coli-infused animals were left untreated and served as septic controls. The sham controls were hemodynamically stable and had normal histological findings. All bacteria-infused animals exhibited signs of septic shock with pronounced hemodynamic reactions. Attenuation of the bacteria-induced increase in pulmonary arterial blood pressure was found in all pretreated animals but most pronounced in the indomethacin-pretreated group which also showed protection against gastric mucosal injury and capillary stasis. TxA2-inhibited animals had aggravated capillary stasis and mucosal injuries. It is concluded that gastric mucosal damage could be modified by drugs influencing the prostanoid system. The "cytoprotective" effect of prostaglandins seem to be of minor importance for the prevention of the gastro-intestinal mucosal injury seen in some series.