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

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.

• Authors: M M Khan, T Yamamoto, H Araki, Y Ijiri, Y Shibuya, M Okamoto, T Kambara
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1182 Issue 1 Pg. 83-93 (Aug 04 1993) ISSN: 0006-3002 [Print] Netherlands
• PMID: 8347690 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Toxins
• Pancreatic Elastase

Topics

• Animals
• Bacterial Toxins (toxicity)
• Blood Pressure
• Colon (blood supply)
• Disease Models, Animal
• Guinea Pigs
• Heart Rate
• Lung (blood supply)
• Pancreatic Elastase (administration & dosage, toxicity)
• Pseudomonas aeruginosa (enzymology)
• Respiration
• Shock, Septic (chemically induced, physiopathology)
• Vascular Resistance (drug effects)