Pathophysiologic Effects of Anatoxin‐a(s) in Anaesthetized Rats: The Influence of Atropine and Artificial Respiration

W. O. Cook, G. A. Iwamoto, D. J. Schaeffer, W. W. Carmichael, V. R. Beasley

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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<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. 1990 Nordic Pharmacological Society

Original languageEnglish (US)
Pages (from-to)151-155
Number of pages5
JournalPharmacology & Toxicology
Volume67
Issue number2
DOIs
StatePublished - Aug 1990

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis

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