Coronary vasoconstriction is the most probable cause of death of rats intoxicated with botulinolysin, a hemolysin produced by Clostridium botulinum.
The pathophysiology of lethal intoxication by botulinolysin (Blyn) was studied using anesthetized rats and isolated rat organs. Intravenous injection of 10,000 and 1000 hemolytic units (HU) of Blyn killed rats rapidly while 100 HU of the toxin did not. Congestion and edema of lungs were observed at autopsies of the rats killed by intoxication. Hemoglobinemia was obvious in rats injected with 1000 HU of Blyn but not in rats with 10,000 HU. Electrocardiograms of the intoxicated rats showed depression of T waves but not changes characteristic of hyperpotassemia. All the rats injected with the above doses of Blyn showed a rapid fall in arterial blood pressure (BP) immediately after the toxin injection, and BP soon recovered in rats injected with 100 HU, partially and transiently in rats with 1000 HU, and not in rats with 10,000 HU of Blyn. Perfusion of Blyn (1 HU/ml) to isolated rat hearts caused a rapid and marked increase in perfusion pressure and cessation of spontaneous heart beat. Acetylsalicylic acid (10(-3) M) and quinacrine dihydrochloride (10(-5) M) did not essentially influence the effects of Blyn on the isolated hearts, but verapamil (10(-6) M) inhibited at least the initial increase in perfusion pressure elicited by Blyn. Spontaneous contractions of the isolated atria were little influenced by Blyn (60 HU/ml). Perfusion pressures of isolated kidneys, lungs and livers were also increased by Blyn (1 HU/ml). The results indicate that Blyn caused vasoconstriction but had little direct effect on myocardium. Based on the above findings, we conclude that coronary vasoconstriction elicited by direct action of Blyn causes acute cardiac dysfunction leading to systemic hypotension and death of the intoxicated animals.
Sugimoto
N
N
Department of Bacterial Toxinology, Osaka University, Japan.
Haque
A
A
Horiguchi
Y
Y
Matsuda
M
M
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001905:Botulinum Toxins / Q000008:administration & dosage / Q000633:toxicity*; D001906:Botulism / Q000401:mortality*; D003014:Clostridium botulinum / Q000737:chemistry*; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D006461:Hemolysis; D007022:Hypotension / Q000139:chemically induced; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011188:Potassium / Q000378:metabolism; D011654:Pulmonary Edema / Q000139:chemically induced / Q000401:mortality; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D014700:Verapamil; D001905:Botulinum Toxins; D011796:Quinacrine; D001241:Aspirin; D011188:Potassium