Cardiovascular and Metabolic Effects of Whole or Fractionated Gram-Negative Bacterial Endotoxin in the Unanesthetized Rhesus Monkey

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Abstract
Rhesus monkeys were infused with endotoxin lipopolysaccharide (LPS) (10 mg/kg [LPS10] or 2.5 mg/kg [LPS2.5]) 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, LPS2.5, 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 hours 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 hours, marked elevation of peripheral vascular resistance developed in monkeys given LPS10 (+113%) and LPS2.5 (+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.