THE EFFECT OF INDOMETHACIN ON THE CARDIOVASCULAR AND METABOLIC RESPONSES TO E. coli ENDOTOXIN IN THE CAT

J. R. PARRATT, R. M. STURGESS

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Abstract

The response of pentobarbitone‐anaesthetized cats to the intravenous administration of E. coli endotoxin (2 mg/kg) consisted of acute pulmonary vasoconstriction (3–5 min after the injection) and a secondary shock phase characterized by delayed systemic hypotension, decreased central venous pressure and cardiac output, and metabolic acidosis with arterial lactate levels three to four times normal. Only one of 25 animals survived 6 hours. Indomethacin (10 mg/kg), administered intravenously 30 min before the endotoxin, reduced both systemic arterial pressure and myocardial blood flow. It abolished the pulmonary vasoconstriction induced by endotoxin. Indomethacin modified some of the characteristic features of the delayed, endotoxin shock phase. Systemic hypotension was not observed and the blood pressure in the indomethacin‐treated cats 1, 2 and 4 h after endotoxin was 30 mmHg higher than in those cats administered endotoxin alone. The decrease in arterial pH was also significantly delayed. Six out of 15 animals survived 6 hours. It is suggested that indomethacin may abolish the initial pulmonary hypertension and oedema by antagonizing the release, or vasoconstrictor effect, of histamine and that part of its action during the shock phase is due to inhibition of prostaglandin release. 1974 British Pharmacological Society

Original languageEnglish
Pages (from-to)177-183
Number of pages7
JournalBritish journal of pharmacology
Volume50
Issue number2
DOIs
Publication statusPublished - Feb 1974

ASJC Scopus subject areas

  • Pharmacology

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