Pathophysiologic effects of anatoxin-a(s) in anaesthetized rats: the influence of atropine and artificial respiration.
The pathophysiologic effects of anatoxin-a(s) from the cyanobacterium Anabaena flos-aquae NRC-525-17 were investigated in anaesthetized adult male Sprague Dawley rats given the toxin by continuous intravenous infusion until death. Rats (n = 6) pretreated with atropine sulfate (50 mg/kg) intraperitoneally survived significantly longer (P less than 0.05) than non-atropinized rats (n = 6), suggesting that the muscarinic effects of anatoxin-a(s) were important in the lethal syndrome. In contrast to rats only given toxin, rats that were pretreated with atropine had a decrease in heart rate and mean blood pressure that followed profound reductions in respiratory tidal and minute volume, suggesting that neuromuscular blockade of the muscles of respiration was the cause of death. Even when survival time of rats was increased by pretreatment with atropine, phrenic nerve amplitude increased, indicating a lack of a depressive effect of anatoxin-a(s) on central mediation of respiration. Rats (n = 3) continuously ventilated during toxin infusion survived a dose more than 4 fold greater than a consistently lethal dose of the toxin. Thus, the cardiovascular effects of anatoxin-a(s) alone could not account for the death of rats. Electromyographic activity recorded from the diaphragms of rats (n = 5) during continuous toxin administration revealed an increase in muscular electrical activity that became more random and finally decreased prior to death, suggesting a toxin-induced neuromuscular blockade in vivo which ultimately was the cause of death of the anatoxin-a(s) dosed rats.
Cook
W O
WO
Department of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois, Urbana 61801.
Iwamoto
G A
GA
Schaeffer
D J
DJ
Carmichael
W W
WW
Beasley
V R
VR
D000769:Anesthesia, Inhalation; D000818:Animals; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology*; D001427:Bacterial Toxins; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D000087522:Cyanobacteria Toxins; D003964:Diaphragm / Q000187:drug effects / Q000502:physiology; D004576:Electromyography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D008297:Male; D008387:Marine Toxins / Q000008:administration & dosage / Q000633:toxicity*; D052998:Microcystins; D011292:Premedication; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects*; D012121:Respiration, Artificial; D015996:Survival Rate; D013997:Time Factors; D014326:Tropanes
D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; D014326:Tropanes; D001285:Atropine; C509783:anatoxin a