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POLYMYXIN B SULPHATE PROTECTS CATS AGAINST THE HAEMODYNAMIC AND METABOLIC EFFECTS OF E. coli ENDOTOXIN
Author(s) -
HUGHESI BERNADETTE,
MADAN B.R.,
PARRATT J.R.
Publication year - 1981
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1981.tb10481.x
Subject(s) - medicine , metabolic acidosis , polymyxin b , polymyxin , hemodynamics , blood pressure , acidosis , cats , pulmonary hypertension , anesthesia , cardiac output , bolus (digestion) , pharmacology , antibiotics , chemistry , biochemistry
1 The intravenous administration of E. coli endotoxin (2mg/kg) in cats anaesthetized with pentobarbitone resulted in an initial acute increase in right atrial pressure and a transient systemic hypotension. Later (from 1 h onwards) there was a progressive decrease in cardiac output, a reduced right atrial filling pressure, systemic hypotension and a profound metabolic acidosis (lactate of 30±1 mg/100ml at 5h compared with 5.1 ±0.5mg/100ml pre‐endotoxin). Only one of eight animals so treated survived 8 h. 2 Polymyxin B sulphate, given intravenously (1 min before endotoxin) as a bolus injection (5 mg/kg) followed by a continuous intravenous infusion (additional 5 mg/kg given over a 30 min period) prevented the endotoxin‐induced pulmonary (right atrial) hypertension but not the acute systemic hypotension. 3 Polymyxin B sulphate reduced the delayed haemodynamic effects of endotoxin (systemic hypotension, decrease in cardiac output); all the eight animals so treated survived 8 h compared with only 1/8 of the controls. 4 Polymyxin B did not prevent the initial (1–3 h) and marked metabolic acidosis following endotoxin; however, after 3h, arterial lactate levels returned towards control whereas in the endotoxin‐alone group they continued to increase until death. 5 The mechanism of this marked protective effect of the antibiotic and the possible clinical repercussions are discussed; the most likely explanation for the protection is in chemical combination with the lipid A moiety of the endotoxin.