Pseudomonal elastase injection causes low vascular resistant shock in guinea pigs.
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.
Khan
M M
MM
Department of Molecular Pathology, Graduate School of Medical Sciences, Kumamoto University, Japan.
Yamamoto
T
T
Araki
H
H
Ijiri
Y
Y
Shibuya
Y
Y
Okamoto
M
M
Kambara
T
T
D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D001794:Blood Pressure; D003106:Colon / Q000098:blood supply; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006339:Heart Rate; D008168:Lung / Q000098:blood supply; D010196:Pancreatic Elastase / Q000008:administration & dosage / Q000633:toxicity*; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D012119:Respiration; D012772:Shock, Septic / Q000139:chemically induced* / Q000503:physiopathology; D014655:Vascular Resistance / Q000187:drug effects*
D001427:Bacterial Toxins; D010196:Pancreatic Elastase