Circulation, Vol 80, 65-77, Copyright © 1989 by American Heart Association
DW Ferguson, WJ Berg, JS Sanders, PJ Roach, JS Kempf and MG Kienzle
Digitalis glycosides exert both excitatory and inhibitory autonomic actions
in animals and produce vasoconstriction in normal humans but produce
vasodilation in heart failure patients. To determine whether or not these
contrasting vascular responses are due to differing autonomic actions of
the drug, we compared the responses to intravenous administration of
Cedilanid-D (0.02 mg/kg) in eight normal subjects (mean age, 23 +/- 1
years) and eight patients with moderate-to-severe heart failure (mean age,
52 +/- 5 years, NYHA Class III-IV). Hemodynamics and efferent sympathetic
nerve activity to muscle (MSNA) were measured during 5-minute periods
before (control) and 20 minutes after drug administration. In the heart
failure patients, Cedilanid-D significantly increased systolic and pulse
pressures, whereas mean arterial pressure was unchanged. There was a
decrease in right atrial pressure and a tendency for a decrease in
pulmonary artery diastolic pressure with a slowing of heart rate. Cardiac
index increased by 24 +/- 7%. Short-term administration of digitalis in
these heart failure patients produced a fall in forearm vascular resistance
(from 37.6 +/- 8.2 to 31.8 +/- 8.1 units, p less than 0.05) and an early,
profound, and sustained decrease in MSNA (from 831.0 +/- 118.4 to 474.4 +/-
103.6 units/100 heart beats, p less than 0.01). Digitalis glycosides
produced different vascular and MSNA responses in the normal subjects. In
the normal volunteers, the drug significantly increased systolic, mean, and
pulse pressures and decreased central venous pressure and heart rate.
Despite the significant increase in arterial pressure, there was no change
in forearm vascular resistance (from 11.7 +/- 1.0 to 12.7 +/- 1.0 units, p
= NS) or MSNA (from 494.8 +/- 88.5 to 369.1 +/- 60.5 units/100 heart beats,
p = NS), suggesting a sympathoexcitatory response in normal subjects. To
determine whether or not the digitalis- induced sympathoinhibition in the
heart failure patients was simply due to an inotropic effect (stimulation
of inhibitory cardiac mechanoreceptors), we studied the responses of seven
additional patients with heart failure before and during administration of
dobutamine (3.4 +/- 0.4 micrograms/kg/min). Dobutamine produced a 34 +/- 3%
increase in cardiac index, no significant change in systemic arterial
pressures, a decrease in pulmonary artery diastolic and right atrial
pressures, and no change in heart rate or forearm vascular resistance (from
30.2 +/- 4.3 to 26.5 +/- 4.7 units, p = NS).(ABSTRACT TRUNCATED AT 400
WORDS)
ARTICLES
Sympathoinhibitory responses to digitalis glycosides in heart failure patients. Direct evidence from sympathetic neural recordings
Department of Internal Medicine, University of Iowa Hospitals, Iowa City.
This article has been cited by other articles:
 |
|
 |
|
  F. Triposkiadis, G. Karayannis, G. Giamouzis, J. Skoularigis, G. Louridas, and J. Butler The sympathetic nervous system in heart failure physiology, pathophysiology, and clinical implications. J. Am. Coll. Cardiol., November 3, 2009; 54(19): 1747 - 1762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. T. Hsu and G. D. Pearson Heart Failure in Children: Part II: Diagnosis, Treatment, and Future Directions Circ Heart Fail, September 1, 2009; 2(5): 490 - 498. [Full Text] [PDF]
|
|
|
|
|
|
S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, K. Michl, et al. 2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation J. Am. Coll. Cardiol., April 14, 2009; 53(15): e1 - e90. [Full Text] [PDF]
|
|
|
|
 |
|
 2005 WRITING COMMITTEE MEMBERS, S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, et al. 2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation Circulation, April 14, 2009; 119(14): e391 - e479. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ahmed Digoxin and Reduction in Mortality and Hospitalization in Geriatric Heart Failure: Importance of Low Doses and Low Serum Concentrations J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2007; 62(3): 323 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Najem, P. Unger, N. Preumont, J.-L. Jansens, A. Houssiere, A. Pathak, O. Xhaet, L. Gabriel, A. Friart, L. De Roy, et al. Sympathetic control after cardiac resynchronization therapy: responders versus nonresponders Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2647 - H2652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ahmed, M. W. Rich, J. L. Fleg, M. R. Zile, J. B. Young, D. W. Kitzman, T. E. Love, W. S. Aronow, K. F. Adams Jr, and M. Gheorghiade Effects of Digoxin on Morbidity and Mortality in Diastolic Heart Failure: The Ancillary Digitalis Investigation Group Trial Circulation, August 1, 2006; 114(5): 397 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M P Frenneaux Autonomic changes in patients with heart failure and in post-myocardial infarction patients Heart, November 1, 2004; 90(11): 1248 - 1255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gheorghiade, K. F. Adams Jr, and W. S. Colucci Digoxin in the Management of Cardiovascular Disorders Circulation, June 22, 2004; 109(24): 2959 - 2964. [Full Text] [PDF]
|
|
|
|
|
|
A. U. Khand, A. C. Rankin, W. Martin, J. Taylor, I. Gemmell, and J. G. F. Cleland Carvedilol alone or in combination with digoxin for the management of atrial fibrillation in patients with heart failure? J. Am. Coll. Cardiol., December 3, 2003; 42(11): 1944 - 1951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Velez-Roa, M. Renard, J.-P. Degaute, and P. van de Borne Peripheral sympathetic control during dobutamine infusion: effects of aging and heart failure J. Am. Coll. Cardiol., November 5, 2003; 42(9): 1605 - 1610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. L. Miller, K. R. Bailey, S. A. Weston, J. C. Burnett Jr., and R. J. Rodeheffer Hemodynamic and plasma atrial natriuretic peptide responses to acute digitalis therapy in patients with normal and impaired left ventricular function Eur J Heart Fail, January 1, 2002; 4(1): 63 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Grassi, C. Turri, G. Seravalle, G. Bertinieri, A. Pierini, and G. Mancia Effects of Chronic Clonidine Administration on Sympathetic Nerve Traffic and Baroreflex Function in Heart Failure Hypertension, August 1, 2001; 38(2): 286 - 291. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Lotze, S. Kaepplinger, A. Kober, B. M. Richartz, D. Gottschild, and H. R. Figulla Recovery of the Cardiac Adrenergic Nervous System After Long-Term {beta}-Blocker Therapy in Idiopathic Dilated Cardiomyopathy: Assessment by Increase in Myocardial 123I-Metaiodobenzylguanidine Uptake J. Nucl. Med., January 1, 2001; 42(1): 49 - 54. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L. Clark Perioperative Treatment of Congestive Heart Failure Seminars in Cardiothoracic and Vascular Anesthesia, November 1, 2000; 4(4): 223 - 235. [Abstract] [PDF]
|
|
|
|
|
|
A. Gabrielsen, V. B. Sorensen, B. Pump, S. Galatius, R. Videbak, P. Bie, J. Warberg, N. J. Christensen, H. Wroblewski, J. Kastrup, et al. Cardiovascular and neuroendocrine responses to water immersion in compensated heart failure Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1931 - H1940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Schunkert The importance of early intervention in CHF -- signs and symptom relief Journal of Renin-Angiotensin-Aldosterone System, March 1, 2000; 1(1_suppl): 17 - 23. [Abstract] [PDF]
|
|
|
|
|
|
P. J. Hauptman and R. A. Kelly Digitalis Circulation, March 9, 1999; 99(9): 1265 - 1270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Grassi, D. Spaziani, G. Seravalle, G. Bertinieri, R. Dell'Oro, C. Cuspidi, and G. Mancia Effects of Amlodipine on Sympathetic Nerve Traffic and Baroreflex Control of Circulation in Heart Failure Hypertension, February 1, 1999; 33(2): 671 - 675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Young, M. Gheorghiade, B. F. Uretsky, J. H. Patterson, and K. F. Adams Jr. Superiority of "triple" drug therapy in heart failure: insights from the PROVED and RADIANCE trials J. Am. Coll. Cardiol., September 1, 1998; 32(3): 686 - 692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. T. Abraham Pharmacologic Management of Chronic Heart Failure: A Review Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 1998; 2(3): 168 - 190. [Abstract] [PDF]
|
|
|
|
 |
|
 J. T. Sullebarger, P. M. D'Ambra, L. C. Clark, L. Thanikarry, and H. L. Fontanet Effect of Digoxin on Ventricular Remodeling and Responsiveness of {beta}-Adrenoceptors in Chronic Volume Overload Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1998; 3(4): 281 - 290. [Abstract] [PDF]
|
|
|
|
|
|
K. Ashino, E. Gotoh, S.-i. Sumita, A. Moriya, and M. Ishii Percutaneous Transluminal Mitral Valvuloplasty Normalizes Baroreflex Sensitivity and Sympathetic Activity in Patients With Mitral Stenosis Circulation, November 18, 1997; 96(10): 3443 - 3449. [Abstract] [Full Text]
|
|
|
|
|
|
P. Ponikowski, T. P. Chua, M. Piepoli, D. Ondusova, K. Webb-Peploe, D. Harrington, S. D. Anker, M. Volterrani, R. Colombo, G. Mazzuero, et al. Augmented Peripheral Chemosensitivity as a Potential Input to Baroreflex Impairment and Autonomic Imbalance in Chronic Heart Failure Circulation, October 21, 1997; 96(8): 2586 - 2594. [Abstract] [Full Text]
|
|
|
|
|
|
G. Grassi, B. M. Cattaneo, G. Seravalle, A. Lanfranchi, M. Pozzi, A. Morganti, S. Carugo, and G. Mancia Effects of Chronic ACE Inhibition on Sympathetic Nerve Traffic and Baroreflex Control of Circulation in Heart Failure Circulation, August 19, 1997; 96(4): 1173 - 1179. [Abstract] [Full Text]
|
|
|
|
|
|
G. Noll, R. R. Wenzel, S. de Marchi, S. Shaw, and T. F. Luscher Differential Effects of Captopril and Nitrates on Muscle Sympathetic Nerve Activity in Volunteers Circulation, May 6, 1997; 95(9): 2286 - 2292. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Brandle, K. P. Patel, W. Wang, and I. H. Zucker Hemodynamic and norepinephrine responses to pacing-induced heart failure in conscious sinoaortic-denervated dogs J Appl Physiol, October 1, 1996; 81(4): 1855 - 1855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. B. James, P. M. McCarthy, J. D. Thomas, R. Vargo, R. E. Hobbs, S. Sapp, and E. Bravo Effect of the Implantable Left Ventricular Assist Device on Neuroendocrine Activation in Heart Failure Circulation, November 1, 1995; 92(9): 191 - 195. [Abstract] [Full Text]
|
|
|
|
|
|
COMMITTEE MEMBERS, J. F. WILLIAMS Jr, M. R. BRISTOW, M. B. FOWLER, G. S. FRANCIS, A. GARSON Jr, B. J. GERSH, D. F. HAMMER, M. A. HLATKY, C. V. LEIER, et al. Guidelines for the Evaluation and Management of Heart Failure : Report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure) Circulation, November 1, 1995; 92(9): 2764 - 2784. [Full Text]
|
|
|
|
|
|
M. Gheorghiade, V. B. Hall, G. Jacobsen, M. Alam, H. Rosman, and S. Goldstein Effects of Increasing Maintenance Dose of Digoxin on Left Ventricular Function and Neurohormones in Patients With Chronic Heart Failure Treated With Diuretics and Angiotensin-Converting Enzyme Inhibitors Circulation, October 1, 1995; 92(7): 1801 - 1807. [Abstract] [Full Text]
|
|
|
|
|
|
M. W. Chapleau, J. T. Cunningham, M. J. Sullivan, R. E. Wachtel, and F. M. Abboud Structural Versus Functional Modulation of the Arterial Baroreflex Hypertension, August 1, 1995; 26(2): 341 - 347. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. C. Kaiser Practice Guidelines in Cardiothoracic Surgery Ann. Thorac. Surg., May 1, 1995; 59(5): 1264 - 1271. [Full Text]
|
|
|
|
 |
|
 M. Packer The Search for the Ideal Positive Inotropic Agent N. Engl. J. Med., July 15, 1993; 329(3): 201 - 202. [Full Text]
|
|
|
|
|
|
M. Packer, M. Gheorghiade, J. B. Young, P. J. Costantini, K. F. Adams, R. J. Cody, L. K. Smith, L. Van Voorhees, L. A. Gourley, M. K. Jolly, et al. Withdrawal of Digoxin from Patients with Chronic Heart Failure Treated with Angiotensin-Converting-Enzyme Inhibitors N. Engl. J. Med., July 1, 1993; 329(1): 1 - 7. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. L. Kulick and S. H. Rahimtoola Current Role of Digitalis Therapy in Patients With Congestive Heart Failure JAMA, June 12, 1991; 265(22): 2995 - 2997. [Abstract] [PDF]
|
|