Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1970 Apr;207(2):357–369. doi: 10.1113/jphysiol.1970.sp009066

The effect of altered thyroid state on atrial intracellular potentials

A S Freedberg, J Gy Papp, E M Vaughan Williams
PMCID: PMC1348711  PMID: 5499024

Abstract

1. A group of rabbits was made hypothyroid by thyroidectomy, and another group was injected daily with L-thyroxine. After an appropriate interval respective alterations in thyroid state were confirmed by measurement of heart weight and of plasma iodine, and the animals' atria were isolated for recording.

2. Measurements were made of atrial contractions, conduction velocity, spontaneous heart rate and maximum driven frequency, and action potentials were recorded with intracellular micro-electrodes.

3. The resting potential and action potential heights were not affected by differences of thyroid state.

4. Atrial arrhythmias are common in hyperthyroidism, rare in myxoedema. The possibility that hypothyroidism might reduce the rate of rise of the action potential, as do anti-arrhythmic drugs, and hyperthyroidism increase it, was investigated. Although the rate of rise was slower in hypothyroid atria at some driving frequencies, this could not alone account for an anti-arrhythmic effect, because at frequencies near the spontaneous heart rate the rate of rise of the action potential was not reduced.

5. The duration of the repolarization phase of the action potential was greatly prolonged in atria from thyroidectomized rabbits, and was shortened in hyperthyroid atria. These changes could account for a reduced probability of arrhythmias in hypothyroidism, and the converse in hyperthyroidism.

Full text

PDF
357

Selected References

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

  1. ABER C. P., THOMPSON G. S. FACTORS ASSOCIATED WITH CARDIAC ENLARGEMENT IN MYXOEDEMA. Br Heart J. 1963 Jul;25:421–424. doi: 10.1136/hrt.25.4.421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. ADAMS C. W. ELECTROCARDIOGRAPHIC CHANGES IN HYPOTHYROIDISM. Dis Chest. 1964 Jul;46:87–88. doi: 10.1378/chest.46.1.87. [DOI] [PubMed] [Google Scholar]
  3. BENFEY B. G., VARMA D. R. CARDIAC AND VASCULAR EFFECTS OF SYMPATHOMIMETIC DRUGS AFTER ADMINISTRATION OF TRI-IODOTHYRONINE AND RESERPINE. Br J Pharmacol Chemother. 1963 Aug;21:174–181. doi: 10.1111/j.1476-5381.1963.tb01513.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BLUMGART H. L., FREEDBERG A. S., KURLAND G. S. Treatment of incapacitated euthyroid cardiac patients with radioactive iodine: summary of results in treatment of 1,070 patients with angina pectoris or congestive failure. J Am Med Assoc. 1955 Jan 1;157(1):1–4. doi: 10.1001/jama.1955.02950180003001. [DOI] [PubMed] [Google Scholar]
  5. BREWSTER W. R., Jr, ISAACS J. P., OSGOOD P. F., KING T. L. The hemodynamic and metabolic interrelationships in the activity of epinephrine, norepinephrine and the thyroid hormones. Circulation. 1956 Jan;13(1):1–20. doi: 10.1161/01.cir.13.1.1. [DOI] [PubMed] [Google Scholar]
  6. DUDEL J., TRAUTWEIN W. Elektrophysiologiche Messungen zur Strophanthinwirkung am Herzmuskel. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1958;232(2):393–407. [PubMed] [Google Scholar]
  7. Darsinos J., Katsilambros N., Papamatheou M., Papadoyanakis N. The response of thyrotoxic tachycardia to Trasicor, a new beta adrenergic blocking agent. Curr Ther Res Clin Exp. 1968 Dec;10(12):626–630. [PubMed] [Google Scholar]
  8. Dohadwalla A. N., Freedberg A. S., Vaughan Williams E. M. The relevance of beta-receptor blockade to ouabain-induced cardiac arrhythmias. Br J Pharmacol. 1969 Jun;36(2):257–267. doi: 10.1111/j.1476-5381.1969.tb09503.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. GOLDSTEIN S., KILLIP T., 3rd CATECHOLAMINE DEPLETION IN THYROTOXICOSIS. EFFECT OF GUANETHIDINE ON CARDIOVASCULAR DYNAMICS. Circulation. 1965 Feb;31:219–227. doi: 10.1161/01.cir.31.2.219. [DOI] [PubMed] [Google Scholar]
  10. GUZ A., KURLAND G. S., FREEDBERG A. S. Heart rate and O2 consumption after triiodothyronine in the myxedematous rabbit. Am J Physiol. 1961 Jan;200:58–60. doi: 10.1152/ajplegacy.1961.200.1.58. [DOI] [PubMed] [Google Scholar]
  11. Gargouïl Y. M., Lenfant J., Tricoche R. Influence de l'imprégnation thyroïdienne sur l'activité transmembranaire du noeud sinoauriculaire de lapin. C R Acad Sci Hebd Seances Acad Sci D. 1966 Mar 28;262(13):1466–1468. [PubMed] [Google Scholar]
  12. HARRISON T. S. ADRENAL MEDULLARY AND THYROID RELATIONSHIPS. Physiol Rev. 1964 Apr;44:161–185. doi: 10.1152/physrev.1964.44.2.161. [DOI] [PubMed] [Google Scholar]
  13. HESS M. E., SHANFELD J. CARDIOVASCULAR AND METABOLIC INTERRELATIONSHIPS BETWEEN THYROXINE AND THE SYMPATHETIC NERVOUS SYSTEM. J Pharmacol Exp Ther. 1965 Jun;148:290–297. [PubMed] [Google Scholar]
  14. Hornbrook K. R., Quinn P. V., Siegel J. H., Brody T. M. Thyroid hormone regulation of cardiac glycogen metabolism. Biochem Pharmacol. 1965 Jun;14(6):925–936. doi: 10.1016/0006-2952(65)90244-3. [DOI] [PubMed] [Google Scholar]
  15. Howitt G., Rowlands D. J. Beta-sympathetic blockade in hyperthyroidism. Lancet. 1966 Mar 19;1(7438):628–631. doi: 10.1016/s0140-6736(66)90825-7. [DOI] [PubMed] [Google Scholar]
  16. Landsberg L., Axelrod J. Influence of pituitary, thyroid, and adrenal hormones on norepinephrine turnover and metabolism in the rat heart. Circ Res. 1968 May;22(5):559–571. doi: 10.1161/01.res.22.5.559. [DOI] [PubMed] [Google Scholar]
  17. MARKS P. A., ROOF B. S. Pericardial effusion associated with myxedema. Ann Intern Med. 1953 Aug;39(2):230–240. doi: 10.7326/0003-4819-39-2-230. [DOI] [PubMed] [Google Scholar]
  18. Margolius H. S., Gaffney T. E. The effects of injected norepinephrine and sympathetic nerve stimulation in hypothyroid and hyperthyroid dogs. J Pharmacol Exp Ther. 1965 Sep;149(3):329–335. [PubMed] [Google Scholar]
  19. McDevitt D. G., Shanks R. G., Hadden D. R., Montgomery D. A., Weaver J. A. The role of the thyroid in the control of heart-rate. Lancet. 1968 May 11;1(7550):998–1000. doi: 10.1016/s0140-6736(68)91109-4. [DOI] [PubMed] [Google Scholar]
  20. McNeill J. H., Brody T. M. The effect of triiodothyronine pretreatment on amine-induced rat cardiac phosphorylase activation. J Pharmacol Exp Ther. 1968 May;161(1):40–46. [PubMed] [Google Scholar]
  21. Noble D. Applications of Hodgkin-Huxley equations to excitable tissues. Physiol Rev. 1966 Jan;46(1):1–50. doi: 10.1152/physrev.1966.46.1.1. [DOI] [PubMed] [Google Scholar]
  22. Noble D., Tsien R. W. Outward membrane currents activated in the plateau range of potentials in cardiac Purkinje fibres. J Physiol. 1969 Jan;200(1):205–231. doi: 10.1113/jphysiol.1969.sp008689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Papp J. G., Vaughan Williams E. M. The effect of bretylium on intracellular cardiac action potentials in relation to its anti-arrhythmic and local anaesthetic activity. Br J Pharmacol. 1969 Oct;37(2):380–390. [PMC free article] [PubMed] [Google Scholar]
  24. Papp J. G., Vaughan Williams E. M. The effect of some catecholamine beta-receptor blocking compounds on the toxicity to the heart of ouabain. Br J Pharmacol. 1969 May;36(1):178P–179P. [PMC free article] [PubMed] [Google Scholar]
  25. Papp J. G., Williams E. M. A comparison of the anti-arrhythmic actions of I.C.I. 50172 and (--)-propranolol and their effects on intracellular cardiac action potentials and other features of cardiac function. Br J Pharmacol. 1969 Oct;37(2):391–399. doi: 10.1111/j.1476-5381.1969.tb10576.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. SCHNECKLOTH R. E., KURLAND G. S., FREEDBERG A. S. Effect of variation in thyroid function on the pressor response to norepinephrine in man. Metabolism. 1953 Nov;2(6):546–555. [PubMed] [Google Scholar]
  27. Szekeres L., Williams E. M. Antifibrillatory action. J Physiol. 1962 Mar;160(3):470–482. doi: 10.1113/jphysiol.1962.sp006860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. THIER M. D., GRAVENSTEIN J. S., HOFFMANN R. G. Thyroxin, reserpine, epinephrine and temperature on atrial rate. J Pharmacol Exp Ther. 1962 May;136:133–141. [PubMed] [Google Scholar]
  29. Taylor R. R., Covell J. W., Ross J., Jr Influence of the thyroid state on left ventricular tension-velocity relations in the intact, sedated dog. J Clin Invest. 1969 Apr;48(4):775–784. doi: 10.1172/JCI106035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Thomas R. C. Membrane current and intracellular sodium changes in a snail neurone during extrusion of injected sodium. J Physiol. 1969 Apr;201(2):495–514. doi: 10.1113/jphysiol.1969.sp008769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Turner P., Hill R. C. A comparison of three beta-adrenergic receptor-blocking drugs in thyrotoxic tachycardia. J Clin Pharmacol J New Drugs. 1968 Jul-Aug;8(4):268–271. doi: 10.1002/j.1552-4604.1968.tb00104.x. [DOI] [PubMed] [Google Scholar]
  32. VAUGHAN WILLIAMS E. M. The mode of action of quinidine on isolated rabbit atria interpreted from intracellular potential records. Br J Pharmacol Chemother. 1958 Sep;13(3):276–287. doi: 10.1111/j.1476-5381.1958.tb00903.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. WILLIAMS E. M. Some observations concerning the mode of action of acetylcholine in isolated rabbit atria. J Physiol. 1958 Mar 11;140(3):327–346. [PMC free article] [PubMed] [Google Scholar]
  34. WILSON W. R., THEILEN E. O., FLETCHER F. W. PHARMACODYNAMIC EFFECTS OF BETA-ADRENERGIC RECEPTOR BLOCKADE IN PATIENTS WITH HYPERTHYROIDISM. J Clin Invest. 1964 Aug;43:1697–1703. doi: 10.1172/JCI105045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. WURTMAN R. J., KOPIN I. J., AXELROD J. Thyroid function and the cardiac disposition of catecholamines. Endocrinology. 1963 Jul;73:63–74. doi: 10.1210/endo-73-1-63. [DOI] [PubMed] [Google Scholar]
  36. Weir R. J., Young J. A., McGuinness J. B. Changes in the electrocardiogram and achilles reflex test during treatment of hypothyroidism. Scott Med J. 1969 Feb;14(2):59–63. doi: 10.1177/003693306901400206. [DOI] [PubMed] [Google Scholar]
  37. Williams E. M. Mode of action of beta receptor antagonists on cardiac muscle. Am J Cardiol. 1966 Sep;18(3):399–405. doi: 10.1016/0002-9149(66)90062-2. [DOI] [PubMed] [Google Scholar]
  38. ZONDEK H. THE ELECTROCARDIOGRAM IN MYXOEDEMA. Br Heart J. 1964 Mar;26:227–232. doi: 10.1136/hrt.26.2.227. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES