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Pseudomonal elastase injection causes low vascular resistant shock in guinea pigs

1993; Elsevier BV; Volume: 1182; Issue: 1 Linguagem: Inglês

10.1016/0925-4439(93)90157-v

1879-260X

Munir Hossain Khan Mohammad, Tetsuro Yamamoto, Haruo Araki, Yuji Ijiri, Yoko Shibuya, Minoru Okamoto, Takeshi Kambara,

Blood properties and coagulation

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.