Pseudomonal elastase injection causes low vascular resistant shock in guinea pigs

doi:10.1016/0925-4439(93)90157-V

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Volume 1182, Issue 1, 4 August 1993, Pages 83-93

https://doi.org/10.1016/0925-4439(93)90157-V Get rights and content

Abstract

An intravenous injection of culture supernatants obtained from an elastase producing strain (IFO-3455) of Pseudomonas aeruginosa exhibited immediate fall of mean arterial blood pressure from 63.8 ± 1.62 to 35.6 ± 2.31 mmHg (P < 0.001), increased heart rate from 249.6 ± 3.86 to 272.6 ± 2.18 beats/min (P < 0.05), and increased respiratory rate from 44.8 ± 2.33 to 68.6 ± 1.60/min(P < 0.01) within 5 min in the anesthetized guinea pigs. In contrast, culture supernatants obtained from an elastase non-producing strain (PA-103) did not cause the cardio-respiratory alterations, even though the same dose of endotoxin was contained in the supernatants. Intravenous or intracardiac injection of purified Pseudomonas aeruginosa elastase (1.2 mg/kg) but not endotoxin (up to 2.0 mg/kg) reproduced the immediate shock followed by death within 45 min in anesthetized or in conscious guinea pigs. Consistently, the shock-inducing ability of pseudomonal elastase was prevented by pretreatment with anti-pseudomonal elastase rabbit F(ab′)₂ antibodies or with a synthetic inhibitor of pseudomonal elastase. Furthermore, intravenous injection of a non-lethal dose of pseudomonal elastase (0.8 mg/kg) immediately decreased peripheral vascular resistance when estimated from a change of perfusion pressure at hindquarter circulation from 74.0 ± 1.00 to 52.6 ± 1.76 mmHg(P<0.05) in association with fall of arterial blood pressure and of cardiac output which was estimated from a change of regional aortic flow. The same low-resistant shock was also observed in rats. We speculate, therefore, that bacterial proteinases may play an important role in human septic shock.

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^☆: This study was presented in part at the 16th meeting of the Japanese Society for microcirculation, held in Tokyo, in 1991; the 14th International Congress of Allergology and Clinical Immunology, held in Kyoto, Japan, in 1991.

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Pseudomonal elastase injection causes low vascular resistant shock in guinea pigs☆

Abstract

Lancet

Chest

Ophthalmology

J. Biol. Chem.

Biochim. Biophys. Acta

Biochim. Biophys. Acta

Biochim. Biophys. Acta

J. Biol. Chem.

J. Appl. Physiol.

J. Immunol.

N. Engl. J. Med.

N. Engl. J. Med.

JAMA

Ann. Intern. Med.

Crit. Care Med.

Crit. Care Med.

J. Surg. Res.