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. 1974 Jan;53(1):288–296. doi: 10.1172/JCI107549

The Neurogenic Vasoconstrictor Effect of Digitalis on Coronary Vascular Resistance

Nason P Hamlin 1,2, James T Willerson 1,2, Hasan Garan 1,2, William John Powell Jr 1,2
PMCID: PMC301464  PMID: 4808642

Abstract

The coronary vasoconstrictor properties of digitals were evaluated in 61 anesthetized, openchest dogs after coronary sinus cannulation and under conditions of a constant heart rate (atrioventricular pacing) and near-constant blood pressure. The contribution of alpha adrenergic receptor stimulation to the digitalis-induced increase in coronary vascular resistance (CVR) was examined. With Na pentobarbital anesthesia (16 dogs), intravenous acetylstrophanthidin (0.5 mg) caused a significant (P<0.05) rise in CVR from 1 through 9 min after injection. The peak increase was +11±2% SE of the control of 1.8±0.2 mm Hg/cm3/min. The mean time to peak effect was 3 min, and to recovery was 21 min. Prior alpha adrenergic receptor blockade with phenoxybenzamine in 11 animals reduced (P<0.05) the acetylstrophanthidin-induced peak of CVR and substantially decreased (P<0.05) the time to recovery (5 min). Intravenous digoxin (1.0 mg) with Na pentobarbital anesthesia (five dogs) had no significant effect on CVR. However, with chloralose and urethane anesthesia (nine dogs) the same dose of digoxin produced a significant rise in CVR from 3 through 30 min. The peak increase was +20±3% of control (1.4±0.1 mm Hg/cm3/min). One-third the dose of intravenous digoxin (0.35 mg) produced a 9.5±1.0% increase in CVR (five additional dogs). Myocardial oxygen consumption did not change significantly in nine dogs after intravenous digoxin. In 10 additional dogs pretreated with phenoxy-benzamine and in 7 dogs pretreated with mecamylamine, the increase in CVR did not occur after 1.0 mg of intravenous digoxin. Thus there is a coronary vasoconstrictor effect of intravenous acetylstrophanthidin and digoxin, of rapid onset, which is mediated through alpha adrenergic receptor stimulation.

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Selected References

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  1. ASTON R., DOMINO E. F. Differential effects of phenobarbital, pentobarbital and diphenylhydantoin on motor cortical and reticular thresholds in the rhesus monkey. Psychopharmacologia. 1961;2:304–317. doi: 10.1007/BF00404118. [DOI] [PubMed] [Google Scholar]
  2. BAYLISS R. I. S., ETHERIDGE M. J., HYMAN A. L., KELLY H. G., McMICHAEL J., REID E. A. S. The effect of digoxin on the right ventricular pressure in hypertensive and ischaemic heart failure. Br Heart J. 1950 Oct;12(4):317–326. doi: 10.1136/hrt.12.4.317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Balcon R., Hoy J., Sowton E. Haemodynamic effects of rapid digitalization following acute myocardial infarction. Br Heart J. 1968 May;30(3):373–376. doi: 10.1136/hrt.30.3.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bloor C. M., Walker D. E., Pensinger R. R. Ouabain induced primary coronary vasoconstriction. 1. Proc Soc Exp Biol Med. 1972 Sep;140(4):1409–1413. doi: 10.3181/00379727-140-36685. [DOI] [PubMed] [Google Scholar]
  5. Cohn J. N., Tristani F. E., Khatri I. M. Cardiac and peripheral vascular effects of digitalis in clinical cardiogenic shock. Am Heart J. 1969 Sep;78(3):318–330. doi: 10.1016/0002-8703(69)90039-8. [DOI] [PubMed] [Google Scholar]
  6. Daggett W. M., Weisfeldt M. L. Influence of the sympathetic nervous system on the response of the normal heart to digitalis. Am J Cardiol. 1965 Sep;16(3):394–405. doi: 10.1016/0002-9149(65)90731-9. [DOI] [PubMed] [Google Scholar]
  7. EXLEY K. A. Depression of autonomic ganglia by barbiturates. Br J Pharmacol Chemother. 1954 Jun;9(2):170–181. doi: 10.1111/j.1476-5381.1954.tb00837.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Klein M., Nejad N. S., Lown B., Hagemeijer F., Barr I. Correlation of the electrical and mechanical changes in the dog heart during progressive digitalization. Circ Res. 1971 Dec;29(6):635–645. [PubMed] [Google Scholar]
  9. Lipp H., Denes P., Gambetta M., Resnekov L. Hemodynamic response to acute intravenous digoxin in patients with recent myocardial infarction and coronary insufficiency with and without heart failure. Chest. 1973 Jun;63(6):862–867. doi: 10.1378/chest.63.6.862. [DOI] [PubMed] [Google Scholar]
  10. Lowenstein E. Morphine "anesthesia"--a perspective. Anesthesiology. 1971 Dec;35(6):563–565. doi: 10.1097/00000542-197112000-00001. [DOI] [PubMed] [Google Scholar]
  11. MASON D. T., BRAUNWALD E. STUDIES ON DIGITALIS. X. EFFECTS OF OUABAIN ON FOREARM VASCULAR RESISTANCE AND VENOUS TONE IN NORMAL SUBJECTS AND IN PATIENTS IN HEART FAILURE. J Clin Invest. 1964 Mar;43:532–543. doi: 10.1172/JCI104939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Pitt B., Elliot E. C., Gregg D. E. Adrenergic receptor activity in the coronary arteries of the unanesthetized dog. Circ Res. 1967 Jul;21(1):75–84. doi: 10.1161/01.res.21.1.75. [DOI] [PubMed] [Google Scholar]
  13. ROSS J., Jr, WALDHAUSEN J. A., BRAUNWALD E. Studies on digitalis. I. Direct effects on peripheral vascular resistance. J Clin Invest. 1960 Jun;39:930–936. doi: 10.1172/JCI104113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Stark J. J., Sanders C. A., Powell W. J., Jr Neurally mediated and direct effects of acetylstrophanthidin on canine skeletal muscle vascular resistance. Circ Res. 1972 Mar;30(3):274–282. doi: 10.1161/01.res.30.3.274. [DOI] [PubMed] [Google Scholar]
  15. Vatner S. F., Higgins C. B., Franklin D., Braunwald E. Effects of a digitalis glycoside on coronary and systemic dynamics in conscious dogs. Circ Res. 1971 Apr;28(4):470–479. doi: 10.1161/01.res.28.4.470. [DOI] [PubMed] [Google Scholar]
  16. Vatner S. F., Higgins C. B., Patrick T., Franklin D., Braunwald E. Effects of cardiac depression and of anesthesia on the myocardial action of a cardiac glycoside. J Clin Invest. 1971 Dec;50(12):2585–2595. doi: 10.1172/JCI106759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. ZUBERBUHLER R. C., BOHR D. F. RESPONSES OF CORONARY SMOOTH MUSCLE TO CATECHOLAMINES. Circ Res. 1965 May;16:431–440. doi: 10.1161/01.res.16.5.431. [DOI] [PubMed] [Google Scholar]

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