AGE-RELATED DIFFERENCES IN RESPONSES TO ENDOTOXIN INFUSION IN UNANESTHETIZED PIGLETS

Newborn endotoxic shock syndrome is associated with high morbidity and mortality, yet presents with different clinical manifestations than i n older patients. To determine the influence of age on hemodynamic and metabolic responses to endotoxin, we developed a chronically instrume nted endotoxic shock model using eight 1-3-day-old and seven 2-3-week- old piglets. Three days after surgery, 10 mg/kg of endotoxin was infus ed intravenously over 10 min in the younger group, and 5-10 mg/kg was given to the older animals. Two older piglets died immediately after i nfusion of 5 mg/kg of endotoxin, and five of the seven died within 4 h r, while all eight younger animals lived longer than 4 hr. Pulmonary a rtery pressure increased significantly after endotoxin in both groups, and there were no differences between groups. Systemic artery pressur e and cardiac index fell by 44 +/- 1 0% and 70 +/- 15%, respectively, 5 min after endotoxin infusion in the older group, while these values did not change significantly in the younger group. Endotoxin infusion also caused greater elevation in pulmonary vascular resistance index i n the older animals. In the later phase, which began 30 min after endo toxin, both groups displayed systemic hypotension and pulmonary hypert ension, and the groups did not differ from one another in this regard. With progression of endotoxic shock, more severe metabolic acidosis d eveloped in the older animals than in the younger animals. Plasma thro mboxane B2 levels in the older group were about double those in younge r piglets. Plasma 6-keto-PGF1alpha and TNF(alpha) levels in both group s were similar and were significantly increased in the later phase. Th ese results demonstrate age-related differences in response to endotox in in unanesthetized infant piglets. The reasons underlying the differ ent age-related responses to endotoxin may be attributed to anatomic a nd physiologic immaturity in the developing newborn; these distinction s may be important in pathogenesis of human disease. (C) 1993 Wiley-Li ss, Inc.