THE EFFECT OF A NEW ANTI‐INFLAMMATORY DRUG, FLURBIPROFEN, ON THE RESPIRATORY, HAEMODYNAMIC AND METABOLIC RESPONSES TO E. coli ENDOTOXIN SHOCK IN THE CAT

Abstract

I The intravenous administration of E. coli endotoxin (2.0 mg/kg) in cats anaesthetized with sodium pentobarbitone resulted in immediate pulmonary hypertension and reductions in lung compliance and systemic arterial Po2. These effects were abolished, or greatly reduced, by the prior intravenous administration of flurbiprofen in doses (100 and 250 ,ug/kg and 1.0 mg/kg) which were devoid of cardiovascular or metabolic effects. Flurbiprofen is thus the most active antipyretic-analgesic drug so far examined in this experimental model. 2 Production of lactate, characteristic of the severe, secondary endotoxin shock phase, was delayed only by the highest dose of flurbiprofen; hypotension, hypoglycaemia and the reduction in cardiac output which occurs during this phase, were unaffected. 3 These findings are discussed with reference to the treatment of the 'shocked lung' syndrome of human septicaemia.

THE POSSIBLE ROLES OF HISTAMINE, 5‐HYDROXYTRYPTAMINE AND PROSTAGLANDIN F2α AS MEDIATORS OF THE ACUTE PULMONARY EFFECTS OF ENDOTOXIN

“…The mechanisms producing this pulmonary lesion are not known; the most likely appear to be sequestration of platelet aggregates and the release of, as yet unidentified, vasoactive agents (Milligan et al, 1974). The administration of purified E. coli endotoxin in the cat results in pulmonary hypertension, oedema, a reduced arterial oxygen tension and a decreased airways compliance (Kuida, Hinshaw, Gilbert & Visscher, 1958;Kuida, Gilbert, Hinshaw, Brunson & Visscher, 1961;Parratt, 1973;Parratt & Sturgess, 1976). This response begins within 1 min of endotoxin administration and pulmonary artery pressure is more than twice normal 3 to 4 min after the injection (Table 1).…”

“…Each has pulmonary effects similar to endotoxin and there is evidence that each is released, at least in some species, following endotoxin administration. A preliminary account of some of the experiments described in this paper was given to a meeting of the Physiological Society (Parratt & Sturgess, 1975a (Parratt, 1973;Parratt & Sturgess, 1976 Waton & West (1966). This procedure reduced abdominal skin (mast cell) histamine by about 90% (see Results section) but had little effect on the histamine content of the intestine or lung.…”

“…Methods Cats, of either sex, were anaesthetized with an intraperitoneal injection of sodium pentobarbitone (35 mg/kg), were subjected to thoracotomy and ventilated with room air by means of a Palmer positive-pressure pump. Systemic (carotid) arterial pressure and dP/dt, pulmonary arterial pressure, right atrial pressure, cardiac output and stroke volume, systolic ejection time, intratracheal pressure, arterial blood gases and pH and arterial lactate and glucose concentrations were measured as described previously (Parratt, 1973;Parratt & Sturgess, 1976).…”

Pulmonary intravascular macrophages in domestic animal species: Review of structural and functional properties

“…Low doses of endotoxin (15 micrograms per kilogram body weight) do not elicit increased pulmonary artery pressure in dogs (Hales et al, 1981;Jacobs et al, 1982) but will cause severe pulmonary hypertension and respiratory distress in calves, sheep, goats, pigs, and cats (Kuida et al, 1961;Reeves et al, 1972;Maxie et al, 1974;Anderson et al, 1975;Olson et al, 1985;Brigham and Meyrick, 1986;Winn et al, 1987). Intravenous application of bacteria (P-hemolytic streptococci, Escherichia coli, and Pseude monas aeruginosa), endotoxin, zymosan-activated (complement-activated) plasma, or liposomes results in an immediate rise of pulmonary arterial pressure in calves, sheep, goats, cats, or pigs (Kuida et al, 1961;Tikoff et al, 1966;Anderson et al, 1975;Parratt and Sturgess, 1976;Crocker et al, 1980;Dehring et al, 1983bDehring et al, , 1984Brigham, 1983,1984;Borg et al, 1984;Niehaus et al, 1984;Parratt et al, 1984;Olson et al, 1985;Teague et al, 1985;Brigham and Meyrick, 1986;Lee et al, 1986;Meadow et al, 1986;Miyamoto et al, 1986). Pulmonary hypertension, lung edema, increased pulmonary shunting, systemic hypotension, and hypoxemia, after endotoxin administration in calves, sheep, pigs, and cats, are attenuated by indomethacin (cyclooxygenase inhibitor), ibuprofen (cyclooxygenase inhibitor with preferential inhibition of thromboxane synthesis), and prostacyclin (short-term vasodilator).…”

Effect of dazoxiben, a specific inhibitor of thromboxane synthetase, on acute pulmonary responses to E. coli endotoxin in anaesthetized cats.

“…The availability of dazoxiben (UK 37248-01), a selective inhibitor of thromboxane synthesis should allow us to determine whether or not thromboxane is largely responsible for these adverse pulmonary changes. This paper summarizes our initial experience with this substance in a well described feline endotoxin shock model (Parratt, 1973;Parratt & Sturgess, 1974;1976;Parratt et al, 1982). A preliminary account of this work was recently given to the British Pharmacological Society (Ball et al, 1982 (Siemens-Elema).…”