Systemic and regional hemodynamic changes after intraperitoneal endotoxin in rabbits: development of a new model of the clinical syndrome of hyperdynamic sepsis.

Rabbits were injected intraperitoneally with sterile saline or Escherichia coli endotoxin (LPS; 50 or 500 micrograms/kg). Sixteen to 18 h later, the animals were anesthetized with ketamine and instrumented to permit measurement of mean arterial pressure, cardiac output (by thermodilution), and regional blood flow (using radioactive microspheres). The animals were allowed to waken fully in a plastic restraining cage prior to measuring systemic and regional hemodynamics. LPS had similar effects regardless of dose, and results from the two dosage groups have been combined. Compared to controls, administrations of LPS resulted in a 29.3% increase in cardiac output (P = .011) and a 22.8% decrease in systemic vascular resistance (P = .0009). Injection of LPS caused significant changes in blood flow to the heart (55.3% increase), small intestine (128.3% increase), portal vein (54.7% increase), and hepatic artery (65.0% decrease). The percentage of cardiac output perfusing the kidneys and hepatic artery was significantly decreased in the endotoxemic group (P = .037 and P = .002, respectively). Injecting LPS resulted in increased relative flow to the heart (P = .024), small intestine (P = .049), and portal vein (P = .041). We conclude that this model reproduces several of the systemic hemodynamic features of the sepsis syndrome in humans. In this model, the hyperdynamic state is associated with vasodilatation in mesenteric (small intestine and colon) and coronary beds and vasoconstriction in the hepatic artery.