Hemodynamics, hypoglycemia, and hepato-pancreatic pathology during the course of endotoxin shock.

The interrelationships between hemodynamics and hypoglycemia during the course of endotoxin shock (ES) has not been fully defined. In the following study, ES (E. coli, 1 mg/kg; n = 7) was induced in a canine model and systemic hemodynamics, glucose metabolism, and hepatic and pancreatic function monitored for 5 hr and compared to time-matched controls (TMC, n = 7). Total peripheral resistance (TPR, dynes-sec-cm-5) increased from 3227 +/- 430 to 4050 +/- 750 at 30 min and then declined to 3050 +/- 1100 at 90 minutes. TPR progressively increased to 6225 +/- 749 by 5 hours. Plasma glucose did not significantly differ from control values (105 +/- 4 mg%) for the first 90 min but then declined to 68 +/- 6 mg% at 4.5 hours. (TMC = 103 +/- 17, P less than 0.05). Serum amylase during the 5 hr protocol was not elevated (TMC = 110.9 +/- 2.4; ES = 100 +/- 1.97%; P greater than 0.1), and light microscopy of the exocrine pancreas demonstrated normal acinar structure. Islet cell structure from the ES group is not significantly different from the TMC. Hepatic histology in the ES group demonstrated periportal and perilobular degranulation and hepatocyte disruption not seen in the TMC. It is hypothesized that ES results in a circle of positive feedback initiated by an increase in TPR and subsequent decrease in flow resulting in hepato-pancreatic ischemia. Ischemic damage is most apparent at the liver and leads to changes in hepatic metabolic activities which contribute to the developing hypoglycemia of the late phase of ES.