Polymyxin B sulphate protects cats against the haemodynamic and metabolic effects of E. coli endotoxin

B. Hughes, B. R. Madan, J. Parratt

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The intravenous administration of E. coli endotoxin (2 mg/kg) in cats anaesthetized with pentobarbitone resulted in an initial acute increase in right atrial pressure and a transient systemic hypotension. Later (from 1h 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/100 ml at 5 h compared with 5.1 ± 0.5 mg/100 ml pre-endotoxin). Only one of eight animals so treated survived 8 h. 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. 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. Polymyxin B did not prevent the initial (1-3h) and marked metabolic acidosis following endotoxin; however, after 3 h, arterial lactate levels returned towards control whereas in the endotoxin-alone group they continued to increase until death. 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.

Original languageEnglish
Pages (from-to)701-707
Number of pages7
JournalBritish Journal of Pharmacology
Volume74
Issue number3
Publication statusPublished - 1981

Fingerprint

Polymyxin B
Endotoxins
Cats
Hemodynamics
Escherichia coli
Hypotension
Atrial Pressure
Acidosis
Cardiac Output
Lactic Acid
Lipid A
Pentobarbital
Intravenous Infusions
Intravenous Administration
Anti-Bacterial Agents
Hypertension
Lung
Injections

ASJC Scopus subject areas

  • Pharmacology

Cite this

Polymyxin B sulphate protects cats against the haemodynamic and metabolic effects of E. coli endotoxin. / Hughes, B.; Madan, B. R.; Parratt, J.

In: British Journal of Pharmacology, Vol. 74, No. 3, 1981, p. 701-707.

Research output: Contribution to journalArticle

@article{4d131e181561426da3a4161a707dd168,
title = "Polymyxin B sulphate protects cats against the haemodynamic and metabolic effects of E. coli endotoxin",
abstract = "The intravenous administration of E. coli endotoxin (2 mg/kg) in cats anaesthetized with pentobarbitone resulted in an initial acute increase in right atrial pressure and a transient systemic hypotension. Later (from 1h 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/100 ml at 5 h compared with 5.1 ± 0.5 mg/100 ml pre-endotoxin). Only one of eight animals so treated survived 8 h. 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. 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. Polymyxin B did not prevent the initial (1-3h) and marked metabolic acidosis following endotoxin; however, after 3 h, arterial lactate levels returned towards control whereas in the endotoxin-alone group they continued to increase until death. 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.",
author = "B. Hughes and Madan, {B. R.} and J. Parratt",
year = "1981",
language = "English",
volume = "74",
pages = "701--707",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Polymyxin B sulphate protects cats against the haemodynamic and metabolic effects of E. coli endotoxin

AU - Hughes, B.

AU - Madan, B. R.

AU - Parratt, J.

PY - 1981

Y1 - 1981

N2 - The intravenous administration of E. coli endotoxin (2 mg/kg) in cats anaesthetized with pentobarbitone resulted in an initial acute increase in right atrial pressure and a transient systemic hypotension. Later (from 1h 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/100 ml at 5 h compared with 5.1 ± 0.5 mg/100 ml pre-endotoxin). Only one of eight animals so treated survived 8 h. 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. 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. Polymyxin B did not prevent the initial (1-3h) and marked metabolic acidosis following endotoxin; however, after 3 h, arterial lactate levels returned towards control whereas in the endotoxin-alone group they continued to increase until death. 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.

AB - The intravenous administration of E. coli endotoxin (2 mg/kg) in cats anaesthetized with pentobarbitone resulted in an initial acute increase in right atrial pressure and a transient systemic hypotension. Later (from 1h 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/100 ml at 5 h compared with 5.1 ± 0.5 mg/100 ml pre-endotoxin). Only one of eight animals so treated survived 8 h. 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. 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. Polymyxin B did not prevent the initial (1-3h) and marked metabolic acidosis following endotoxin; however, after 3 h, arterial lactate levels returned towards control whereas in the endotoxin-alone group they continued to increase until death. 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.

UR - http://www.scopus.com/inward/record.url?scp=0019777203&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0019777203&partnerID=8YFLogxK

M3 - Article

C2 - 6170378

AN - SCOPUS:0019777203

VL - 74

SP - 701

EP - 707

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 3

ER -