Archives of Toxicology

, Volume 62, Issue 2–3, pp 161–166 | Cite as

Effects of amyl nitrite on circulation, respiration and blood homoeostasis in cyanide poisoning

  • R. Klimmek
  • C. Krettek
Original Investigations

Abstract

The effects of intravenously (i.v.) administered or inhaled amyl nitrite (AN) were followed under chloralose anaesthesia in intact and cyanide-poisoned, spontaneously breathing beagles. The i.v. doses of AN were 0.03 and 0.15 mmol/kg and the i.v. dose of KCN was 0.06 mmol/kg. AN was inhaled in a closed system at 0.15 mmol/kg without previous poisoning and, in addition, at 0.074 mmol/kg (two ampoules at 0.3 ml AN) during artificial ventilation after poisoning with 0.045 mmol KCN/kg i.v., Mean arterial pressure decreased by 15 and 40 mmHg, respectively, after i.v. injection of AN, associated with bradycardia and lowered peripheral blood flow. Respiratory minute volume rose by 65% with the higher dose. Arterial pO2 decreased by 20 mmHg while pCO2 rose by 6 mmHg. Within 30 min of injection, these changes were only partially reversible. Similar results were obtained following inhalation of AN in a closed system. Lactic acidosis and lowering of pH were produced by the i.v. route, but not by inhalation. Total haemoglobin increased. The lethality of KCN was abolished with AN doses that produced 10–30% ferrihaemoglobin. Artificial ventilation and simultaneous inhalation of AN after poisoning with lethal doses of KCN turned out to be ineffective therapeutic measures. The findings are compared with those of other papers dealing with cyanide poisoning and AN. It is pointed out that, for the present, there is no experimental proof for another antidotal mechanism of action of AN than ferrihaemoglobin formation.

Key words

Amyl nitrite Ferrihaemoglobin Cyanide Circulation Blood gases 

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References

  1. Chen KK, Rose CL (1952) Nitrite and thiosulfate therapy in cyanide poisoning. JAMA 149: 113–119Google Scholar
  2. Chen KK, Rose CL (1956) Treatment of acute cyanide poisoning. JAMA 162: 1154–1156Google Scholar
  3. Chen KK, Rose CL, Clowes GHA (1933) Amyl nitrite and cyanide poisoning. JAMA 100: 1920–1922Google Scholar
  4. Christel D, Eyer P, Hegemann M, Kiese M, Lörcher W, Weger N (1977) Pharmacokinetics of cyanide in poisoning of dogs, and the effect of 4-dimethylaminophenol or thiosulfate. Arch Toxicol 38: 177–189Google Scholar
  5. Feelisch M, Noack EA (1987) Correlation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase. Eur J Pharmacol 139: 19–30Google Scholar
  6. Hutchinson PJA, Palmer RMJ, Moncada S (1987) Comparative pharmacology of EDRF and nitric oxide on vascular strips. Eur J Pharmacol 141: 445–451Google Scholar
  7. Kiese M, Schöber JG, Weger N (1968) Versuche am Menschen zur Kinetik der Ferrihämoglobinbildung durch Aminophenole und Nitrit. Naunyn-Schmiedeberg's Arch Pharmacol Exp Pathol 260: 152–153Google Scholar
  8. Klimmek R, Eyer P (1986) Pharmacokinetics and pharmacodynamics of the oxime HI6 in dogs. Arch Toxicol 59: 272–278Google Scholar
  9. Klimmek R, Fladerer H, Szinicz L, Weger N, Kiese M (1979a) Effects of 4-dimethylaminophenol and Co2EDTA on circulation, respiration, and blood homeostasis in dogs. Arch Toxicol 42: 75–84Google Scholar
  10. Klimmek R, Fladerer H, Weger N (1979b) Circulation, respiration, and blood homeostasis in cyanide-poisoned dogs after treatment with 4-dimethylaminophenol or cobalt compounds. Arch Toxicol 43: 121–133Google Scholar
  11. Klimmek R, Krettek C, Werner HW (1988) Ferrihaemoglobin formation by amyl nitrite and sodium nitrite in different species in vivo and in vitro. Arch Toxicol 62: 152–160Google Scholar
  12. Mercker H, Roser F (1957) Über Kreislauf- und Stoffwechselreaktionen bei der spezifischen Behandlung der Blausäurevergiftung. Arch Exp Pathol Pharmacol 230: 125–141Google Scholar
  13. Paulet G (1957) Valeur des sels organiques du cobalt dans le traitement de l'intoxication cyanhydrique. C R Soc Biol (Paris) 151: 1532–1535Google Scholar
  14. Paulet G (1958) Intoxication cyanhydrique et chélates de cobalt. J Physiol (Paris) 50: 438–442Google Scholar
  15. Tauberger G, Klimmer OR (1963) Tierexperimentelle Untersuchungen einiger Kobaltverbindungen nach intravenöser Injektion. Arch Int Pharmacodyn Thér 143: 219–239Google Scholar
  16. Vick JA, Froehlich HL (1985) Studies of cyanide poisoning. Arch Int Pharmacodyn Thér 273: 314–322Google Scholar
  17. Weger N (1969) Therapie der Blausäurevergiftung durch Ferrihämoglobinbildung. Habilitationsschrift. Ludwig-Maximilian-Universität München, 1970Google Scholar
  18. West JB (1977) Ventilation/blood flow and gas exchange. Third ed. Reprinted 1978. Blackwell Scientific Publications, Oxford, London, Edinburgh, MelbourneGoogle Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • R. Klimmek
    • 1
  • C. Krettek
    • 1
  1. 1.Walther-Straub-Institut für Pharmakologie und Toxikologie der Ludwig-Maximilians-UniversitätMünchen 2Federal Republic of Germany

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