| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
Effects of bacterial thiol-activated hemolysins, botulinolysin (BL) of Clostridium botulinum and theta toxin of C.perfringens, on the pulmonary circulation of the animals were studied using whole rats, isolated aortic rings, and cultured endothelial cells.
1. Rats intoxicated with 1,000 HU of BL showed left heart failure with progressive bradycardia and hypotension, and died 15.6(]SY.+-。[)2,0 min after the toxin injection. On the other hand, rats intoxicated with 10,000 HU of theta toxin showed right heart failure with tachynea, lung edema, clot formation in right atrial and ventricular cavities, and liver congestion, and died 21.8(]SY.+-。[)2.8 min after the injection.
2. In vitro perfusion of BL into isolated rat hearts caused marked increase in resistance of coronary circulation while perfusion of theta toxin did just a little.
3. Acetylcholine-induced endothelium-dependent relaxation of isolated rat aortic rings was inhibited by both hemolysins. The extent of rightward shifts of concentration-response curve of acetylcholine by 1 HU/ml of BL and 1 HU/ml of theta toxin were almost the same.
4. Swine and gunea pig aortic endothelial cells were very much sensitive to both hemolysins comparing with other nuclearated mammalian cells in culture. No significant difference was obserrved between 50% effective concentrations of BL and that of theta toxin in their cytotoxic action against swine and guinea pig endothelial cells culture.
The results obtained in this study show taht both hemolysins act on endothelial cells in vivo. Theta toxin preferentially acts on the pulmonary circulation system while BL acts preferentially on the coronary circulation system, though both hemolysins act similarly on aortic endothelial cells in vitro and in site. The results suggest theta toxin as a possible causative agent for adult respiratory distress syndrome in gas gangrenes.
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