Skip to main content
The Yale Journal of Biology and Medicine logoLink to The Yale Journal of Biology and Medicine
. 1991 Mar-Apr;64(2):143–153.

Cocaine alters heart rate dynamics in conscious ferrets.

B S Stambler 1, J P Morgan 1, J Mietus 1, G B Moody 1, A L Goldberger 1
PMCID: PMC2589478  PMID: 1750225

Abstract

This study was designed to test the hypothesis that cocaine intoxication induces distinctive alterations in sinus rhythm heart rate dynamics. Time-series and spectral analysis techniques were used to examine the effects of lethal doses of cocaine on heart rate variability in conscious, restrained ferrets. In all animals (n = 5), cocaine administration resulted in a marked decrease in sinus rhythm heart rate variability prior to sudden death. Heart rate variability (coefficient of variation of heart rate) just prior to death (0.018 +/- 0.005) was significantly (p less than 0.02) decreased compared to that at baseline prior to cocaine administration (0.061 +/- 0.022). There was also a significant (p less than 0.02) decrease in total spectral power prior to death compared to baseline. Transient low-frequency (0.04-0.10 Hz) oscillations in heart rate were also noted in three of the five animals following cocaine administration. There were, however, no significant changes in mean heart rate in response to cocaine. Alterations in heart rate dynamics were not seen in three saline-treated controls. Lethal effects of cocaine included ventricular arrhythmias (n = 2) and seizures (n = 3). One animal developed transient ST segment elevations that were consistent with coronary vasospasm. In conclusion, lethal doses of cocaine in the conscious ferret induce characteristic alterations in heart rate dynamics. These abnormalities (loss of heart rate variability and the appearance of low-frequency heart rate oscillations) are similar to those reported previously in certain patients at high risk of sudden cardiac death due to organic heart disease.

Full text

PDF
143

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akselrod S., Gordon D., Madwed J. B., Snidman N. C., Shannon D. C., Cohen R. J. Hemodynamic regulation: investigation by spectral analysis. Am J Physiol. 1985 Oct;249(4 Pt 2):H867–H875. doi: 10.1152/ajpheart.1985.249.4.H867. [DOI] [PubMed] [Google Scholar]
  2. Akselrod S., Gordon D., Ubel F. A., Shannon D. C., Berger A. C., Cohen R. J. Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science. 1981 Jul 10;213(4504):220–222. doi: 10.1126/science.6166045. [DOI] [PubMed] [Google Scholar]
  3. Bedotto J. B., Lee R. W., Lancaster L. D., Olajos M., Goldman S. Cocaine and cardiovascular function in dogs: effects on heart and peripheral circulation. J Am Coll Cardiol. 1988 Jun;11(6):1337–1342. doi: 10.1016/0735-1097(88)90301-4. [DOI] [PubMed] [Google Scholar]
  4. Bigger J. T., Jr, Kleiger R. E., Fleiss J. L., Rolnitzky L. M., Steinman R. C., Miller J. P. Components of heart rate variability measured during healing of acute myocardial infarction. Am J Cardiol. 1988 Feb 1;61(4):208–215. doi: 10.1016/0002-9149(88)90917-4. [DOI] [PubMed] [Google Scholar]
  5. Catravas J. D., Waters I. W. Acute cocaine intoxication in the conscious dog: studies on the mechanism of lethality. J Pharmacol Exp Ther. 1981 May;217(2):350–356. [PubMed] [Google Scholar]
  6. Goldberger A. L., Findley L. J., Blackburn M. R., Mandell A. J. Nonlinear dynamics in heart failure: implications of long-wavelength cardiopulmonary oscillations. Am Heart J. 1984 Mar;107(3):612–615. doi: 10.1016/0002-8703(84)90120-0. [DOI] [PubMed] [Google Scholar]
  7. Goldberger A. L., Rigney D. R., Mietus J., Antman E. M., Greenwald S. Nonlinear dynamics in sudden cardiac death syndrome: heartrate oscillations and bifurcations. Experientia. 1988 Dec 1;44(11-12):983–987. doi: 10.1007/BF01939894. [DOI] [PubMed] [Google Scholar]
  8. Goldberger A. L., West B. J. Fractals in physiology and medicine. Yale J Biol Med. 1987 Sep-Oct;60(5):421–435. [PMC free article] [PubMed] [Google Scholar]
  9. Gradman A. H. Cardiac effects of cocaine: a review. Yale J Biol Med. 1988 Mar-Apr;61(2):137–147. [PMC free article] [PubMed] [Google Scholar]
  10. Graham M. H., Abboud F. M., Eckstein J. W. Effect of cocaine on cardiovascular responses in intact dogs. J Pharmacol Exp Ther. 1965 Oct;150(1):46–52. [PubMed] [Google Scholar]
  11. Isner J. M., Estes N. A., 3rd, Thompson P. D., Costanzo-Nordin M. R., Subramanian R., Miller G., Katsas G., Sweeney K., Sturner W. Q. Acute cardiac events temporally related to cocaine abuse. N Engl J Med. 1986 Dec 4;315(23):1438–1443. doi: 10.1056/NEJM198612043152302. [DOI] [PubMed] [Google Scholar]
  12. Jonsson S., O'Meara M., Young J. B. Acute cocaine poisoning. Importance of treating seizures and acidosis. Am J Med. 1983 Dec;75(6):1061–1064. doi: 10.1016/0002-9343(83)90889-6. [DOI] [PubMed] [Google Scholar]
  13. Kleiger R. E., Miller J. P., Bigger J. T., Jr, Moss A. J. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol. 1987 Feb 1;59(4):256–262. doi: 10.1016/0002-9149(87)90795-8. [DOI] [PubMed] [Google Scholar]
  14. Kobayashi M., Musha T. 1/f fluctuation of heartbeat period. IEEE Trans Biomed Eng. 1982 Jun;29(6):456–457. doi: 10.1109/TBME.1982.324972. [DOI] [PubMed] [Google Scholar]
  15. Lange R. A., Cigarroa R. G., Yancy C. W., Jr, Willard J. E., Popma J. J., Sills M. N., McBride W., Kim A. S., Hillis L. D. Cocaine-induced coronary-artery vasoconstriction. N Engl J Med. 1989 Dec 7;321(23):1557–1562. doi: 10.1056/NEJM198912073212301. [DOI] [PubMed] [Google Scholar]
  16. Mittleman R. E., Wetli C. V. Death caused by recreational cocaine use. An update. JAMA. 1984 Oct 12;252(14):1889–1893. [PubMed] [Google Scholar]
  17. Myers G. A., Martin G. J., Magid N. M., Barnett P. S., Schaad J. W., Weiss J. S., Lesch M., Singer D. H. Power spectral analysis of heart rate variability in sudden cardiac death: comparison to other methods. IEEE Trans Biomed Eng. 1986 Dec;33(12):1149–1156. doi: 10.1109/TBME.1986.325694. [DOI] [PubMed] [Google Scholar]
  18. Nanji A. A., Filipenko J. D. Asystole and ventricular fibrillation associated with cocaine intoxication. Chest. 1984 Jan;85(1):132–133. doi: 10.1378/chest.85.1.132. [DOI] [PubMed] [Google Scholar]
  19. Pitts D. K., Udom C. E., Marwah J. Cardiovascular effects of cocaine in anesthetized and conscious rats. Life Sci. 1987 Mar 16;40(11):1099–1111. doi: 10.1016/0024-3205(87)90573-x. [DOI] [PubMed] [Google Scholar]
  20. Sands K. E., Appel M. L., Lilly L. S., Schoen F. J., Mudge G. H., Jr, Cohen R. J. Power spectrum analysis of heart rate variability in human cardiac transplant recipients. Circulation. 1989 Jan;79(1):76–82. doi: 10.1161/01.cir.79.1.76. [DOI] [PubMed] [Google Scholar]
  21. Saul J. P., Arai Y., Berger R. D., Lilly L. S., Colucci W. S., Cohen R. J. Assessment of autonomic regulation in chronic congestive heart failure by heart rate spectral analysis. Am J Cardiol. 1988 Jun 1;61(15):1292–1299. doi: 10.1016/0002-9149(88)91172-1. [DOI] [PubMed] [Google Scholar]
  22. Sayers B. M. Analysis of heart rate variability. Ergonomics. 1973 Jan;16(1):17–32. doi: 10.1080/00140137308924479. [DOI] [PubMed] [Google Scholar]
  23. Schwartz A. B., Janzen D., Jones R. T., Boyle W. Electrocardiographic and hemodynamic effects of intravenous cocaine in awake and anesthetized dogs. J Electrocardiol. 1989 Apr;22(2):159–166. doi: 10.1016/0022-0736(89)90086-1. [DOI] [PubMed] [Google Scholar]
  24. Smith H. W., 3rd, Liberman H. A., Brody S. L., Battey L. L., Donohue B. C., Morris D. C. Acute myocardial infarction temporally related to cocaine use. Clinical, angiographic, and pathophysiologic observations. Ann Intern Med. 1987 Jul;107(1):13–18. doi: 10.7326/0003-4819-107-1-13. [DOI] [PubMed] [Google Scholar]
  25. Trouve R., Nahas G. Nitrendipine: an antidote to cardiac and lethal toxicity of cocaine. Proc Soc Exp Biol Med. 1986 Dec;183(3):392–397. doi: 10.3181/00379727-183-3-rc1. [DOI] [PubMed] [Google Scholar]

Articles from The Yale Journal of Biology and Medicine are provided here courtesy of Yale Journal of Biology and Medicine

RESOURCES