Cardiovascular and metabolic effects of whole or fractionated gram negative bacterial endotoxin in the unanesthetized rhesus monkey

Rhesus monkeys were infused with endotoxin lipopolysaccharide (LPS) (10 mg/kg [LPS₁₀] or 2.5 mg/kg [LPS(2.5)]) or with fractions of LPS containing 6.3% lipid (PS₁) or 0.5% lipid (PS₂) (2.5 mg/kg). Systemic and regional hemodynamics, leukocyte counts, blood gases, pH, and plasma bradykinin concentration were measured. Monkeys receiving LPS₁₀, LPS(2.5) or PS₁ became hypotensive (mean blood pressure -37±10 mm Hg) and had decreased peripheral vascular resistance (-10 to ^-24% of the base line), compensated metabolic acidosis, and elevated plasma bradykinin concentrations (14±6 ng/ml) 2 hr after infusion. Vasodilation occurred in coronary, hepatic, and splanchnic vasculature; vasoconstriction occurred in the spleen. Cardiac output was diverted from muscle to viscera. Monkeys receiving PS₂ were normotensive with elevated peripheral vascular resistance (+46%) and no measurable plasma bradykinin concentration. By 6 hr marked elevation of peripheral vascular resistance developed in monkeys given LPS₁₀ (+113%) and LPS(2.5) (+57%). Monkeys receiving PS₁ returned to base line values, but monkeys receiving PS₂ remained unchanged. Leukopenia (-50 to -65%) was persistent only in monkeys receiving LPS or PS₁. Toxicity of LPS apparently depends on the lipid portions of the molecule. Vasodilation and bradykinin generation are correlated with persistent granulocytopenia. Late toxicity may be independent of early cardiovascular events.