Mortality, temporal substrate and insulin responses to endotoxic shock in zero, ten and twenty-eight day old rats

Neonatal sepsis is a significant health problem. However, to our knowledge, the temporal substrates and insulin response to endotoxin have not been characterized in the young animal to guide the investigations of glucoregulation in septic shock in the newborn. We characterized the temporal response to endotoxin in the developing rat. Sprague-Dawley rats were given intraperitoneal Salmonella enteritidis endotoxin in high and low lethal doses to zero, ten and 28 day old rats. Mortality, temporal glucose, lactate, hepatic glycogen and insulin were monitored. Mortality experiments show the ten day old rat is 300 times as sensitive to endotoxin as the 28 day old rat. Plasma glucose concentration increased in the high mortality groups by 120 minutes in the zero and ten day old rats (102 +/- 4 milligrams per deciliter, 119 +/- 6 milligrams per deciliter, respectively, and by 60 minutes in the 28 day old rats (223 +/- 12 milligrams per deciliter). The plasma glucose level decreased to 52 +/- 3 milligrams per deciliter by 240 minutes in the ten day old and by 180 minutes to 99 +/- 8 milligrams per deciliter in the 28 day high mortality groups. Peak lactic acid levels in the high lethality groups were zero day 2.8 +/- 0.2 millimoles per liter in zero day old rats, 3.3 +/- 0.2 millimoles per liter in 28 day old rats. Glycogen in the liver decreased rapidly by 120 minutes in all age groups. Plasma insulin concentration did not elevate significantly in zero and ten day old rats. In the 28 day old rat, insulin concentration increased by 120 minutes to 52 +/- 17 microunits per milliliter. Insulin glucose ratios were also elevated in the 28 day old endotoxin treated rat, indicating hyperinsulinemia. Thus, temporal substrates and insulin responses to endotoxin differ with animal age.