Pathodynamics of intoxication in rats and mice by enterotoxin of Clostridium perfringens type A.
The pathodynamics of lethal intoxication in rats and mice by i.v. administration of enterotoxin of Clostridium perfringens type A was studied using whole animals and isolated organs. A lethal i.v. dose (50 micrograms/kg) of enterotoxin killed anesthetized rats and mice within 4-15 min. Rapid changes of ECG pattern suggestive of hyperpotassemia, rapid fall of blood pressure and transient hyperpnea followed by respiratory depression were observed. Analysis of plasma levels of cations revealed hyperpotassemia in both animal species. On the other hand, enterotoxin (up to 100 micrograms) showed little direct cardiotoxicity on the isolated heart. ECG changes produced by i.v. injection of KCl (0.5 ml of 50 mM) mimicked the ECG changes observed in the intoxicated rats injected with a lethal dose of enterotoxin. Perfusion of rat isolated organs showed that potassium concentration in the eluent from the liver (but not lungs or lower extremities) increased markedly within 1-2 min after the administration of enterotoxin. The amount of potassium liberated from a rat liver was about 133 mumoles, which is sufficient to increase the plasma level of potassium to more than 10 mM. In addition to potassium, cytoplasmic enzymes, such as glutamate oxalacetate transaminase, glutamate pyruvate transaminase and lactate dehydrogenase, were also liberated from the intoxicated liver, indicating that potassium was liberated from hepatocytes by the change in membrane permeability produced by enterotoxin. It is concluded that hyperpotassemia elicited by the cytotoxic action of enterotoxin on hepatocytes caused cardiac failure leading to the death of the intoxicated animals.
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, R.O.C.
N
N
Sugimoto
Y M
YM
Chen
S Y
SY
Lee
M
M
Matsuda
C Y
CY
Lee
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002412:Cations; D003016:Clostridium perfringens; D003600:Cytosol / Q000201:enzymology; D004562:Electrocardiography / Q000187:drug effects; D004768:Enterotoxins / Q000633:toxicity*; D006321:Heart / Q000187:drug effects; D006454:Hemoglobins / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008813:Mice, Inbred ICR; D010477:Perfusion; D011189:Potassium Chloride / Q000633:toxicity; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D012119:Respiration / Q000187:drug effects
D002412:Cations; D004768:Enterotoxins; D006454:Hemoglobins; C035598:enterotoxin, Clostridium; D011189:Potassium Chloride