Beta endorphin, a vasoconstrictor during septic shock

A relationship between increased peripheral resistance (TPRI) and decreased cardiac index (CI) and mortality from sepsis has been suggested. The relationship between endogenous opiates and this response was evaluated. Chronically instrumented sheep were given E. coli endotoxin (LPS, 1.5 mcg/kg × 30 minutes). In one study, survivors (n = 9) and nonsurvivors (n = 11) of LPS were compared along with survivors (n = 8) of half the dose of LPS. In a second study, two groups of animals received naloxone: one (n = 11) had a bolus of 2 mg/kg followed by a 2 mg/kg/hr continuous infusion started 30 minutes before LPS while the other had the bolus and infusion started 1 hour after LPS was begun. Both vasoconstrictive and vasodilative phases were seen. Vasoconstriction was associated with elevated beta endorphin levels, a pattern sustained until death in the nonsurvivors. Both pre- and posttreatment with naloxone lessened the maximum increase in total peripheral resistance index compared with untreated sheep. The vasoconstrictive aspects of the response to LPS correlated with elevated beta endorphin levels and with mortality. This vascular response is attenuated with naloxone blockade.