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. 1995 Oct;74(4):431–436. doi: 10.1136/hrt.74.4.431

Reductions in muscle sympathetic nerve activity after long-term metoprolol for dilated cardiomyopathy: preliminary observations.

M A Rahman 1, K Hara 1, P A Daly 1, E D Wigle 1, J S Floras 1
PMCID: PMC484052  PMID: 7488460

Abstract

OBJECTIVE--To determine whether efferent muscle sympathetic nerve activity diminishes in subjects with dilated cardiomyopathy who improve after long term treatment with metoprolol. METHODS--Microneurographic, echocardiographic, plethysmographic, and neurohumoral data were obtained immediately before and 20 months after the addition of beta blockade in seven subjects with idiopathic dilated cardiomyopathy with clinical deterioration despite conventional treatment. RESULTS--Six subjects (three men, three women, aged 24-62 years) were restudied after a mean (SEM) of 20 (2.4) months treatment with metoprolol (45.8 (2.6) mg/d). Long term treatment was associated with decreases in left ventricular end diastolic and end systolic diameter (P < 0.005), left ventricular mass index (P < 0.05), and atrial natriuretic factor (P < 0.05), and increases in fractional shortening (P < 0.05) and mean blood pressure (P < 0.05). There was a 50% reduction in peroneal muscle sympathetic nerve activity (from 49.2 (10.1) to 24.5 (4.7) bursts/min; (P < 0.005) and a 62% decrease in calf vascular resistance (from 56.2 (4.4) to 21.2 (5.7) units; P < 0.005). This reduction in pulse synchronous nerve activity was not simply a function of bradycardia (heart rate fell from 94.2 (4.6) to 62.8 (5.7) beats/min; P < 0.005) since muscle sympathetic burst incidence also decreased (from 51 (8.7) to 37.5 (5.2) bursts/100 heart beats; P < 0.05). Similar haemodynamic improvement was observed in the seventh subject, who was switched to sotalol 200 mg/d and restudied after 20 months, but burst frequency was 50% higher and calf vascular resistance 93% higher. CONCLUSIONS--Muscle sympathetic nerve activity and calf vascular resistance decrease in patients with dilated cardiomyopathy who improve after long term treatment with metoprolol. Inhibition of central sympathetic outflow may be one mechanism by which metoprolol benefits such subjects.

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Selected References

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  1. Andersson B., Hamm C., Persson S., Wikström G., Sinagra G., Hjalmarson A., Waagstein F. Improved exercise hemodynamic status in dilated cardiomyopathy after beta-adrenergic blockade treatment. J Am Coll Cardiol. 1994 May;23(6):1397–1404. doi: 10.1016/0735-1097(94)90383-2. [DOI] [PubMed] [Google Scholar]
  2. Bristow M. R., Ginsburg R., Umans V., Fowler M., Minobe W., Rasmussen R., Zera P., Menlove R., Shah P., Jamieson S. Beta 1- and beta 2-adrenergic-receptor subpopulations in nonfailing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective beta 1-receptor down-regulation in heart failure. Circ Res. 1986 Sep;59(3):297–309. doi: 10.1161/01.res.59.3.297. [DOI] [PubMed] [Google Scholar]
  3. Bristow M. R., Hershberger R. E., Port J. D., Minobe W., Rasmussen R. Beta 1- and beta 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium. Mol Pharmacol. 1989 Mar;35(3):295–303. [PubMed] [Google Scholar]
  4. Cohn J. N., Levine T. B., Olivari M. T., Garberg V., Lura D., Francis G. S., Simon A. B., Rector T. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med. 1984 Sep 27;311(13):819–823. doi: 10.1056/NEJM198409273111303. [DOI] [PubMed] [Google Scholar]
  5. Cowley A. J., Rowley J. M., Stainer K., Hampton J. R. The effect of the angiotensin converting enzyme inhibitor, enalapril, on exercise tolerance and abnormalities of limb blood flow and respiratory function in patients with severe heart failure. Eur Heart J. 1993 Jul;14(7):964–968. doi: 10.1093/eurheartj/14.7.964. [DOI] [PubMed] [Google Scholar]
  6. Currie P. J., Kelly M. J., McKenzie A., Harper R. W., Lim Y. L., Federman J., Anderson S. T., Pitt A. Oral beta-adrenergic blockade with metoprolol in chronic severe dilated cardiomyopathy. J Am Coll Cardiol. 1984 Jan;3(1):203–209. doi: 10.1016/s0735-1097(84)80449-0. [DOI] [PubMed] [Google Scholar]
  7. Devereux R. B., Reichek N. Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. Circulation. 1977 Apr;55(4):613–618. doi: 10.1161/01.cir.55.4.613. [DOI] [PubMed] [Google Scholar]
  8. Engelmeier R. S., O'Connell J. B., Walsh R., Rad N., Scanlon P. J., Gunnar R. M. Improvement in symptoms and exercise tolerance by metoprolol in patients with dilated cardiomyopathy: a double-blind, randomized, placebo-controlled trial. Circulation. 1985 Sep;72(3):536–546. doi: 10.1161/01.cir.72.3.536. [DOI] [PubMed] [Google Scholar]
  9. Ferguson D. W., Berg W. J., Sanders J. S. Clinical and hemodynamic correlates of sympathetic nerve activity in normal humans and patients with heart failure: evidence from direct microneurographic recordings. J Am Coll Cardiol. 1990 Nov;16(5):1125–1134. doi: 10.1016/0735-1097(90)90544-y. [DOI] [PubMed] [Google Scholar]
  10. Floras J. S., Hara K. Sympathoneural and haemodynamic characteristics of young subjects with mild essential hypertension. J Hypertens. 1993 Jun;11(6):647–655. doi: 10.1097/00004872-199306000-00009. [DOI] [PubMed] [Google Scholar]
  11. Floras J. S. Sympathoinhibitory effects of atrial natriuretic factor in normal humans. Circulation. 1990 Jun;81(6):1860–1873. doi: 10.1161/01.cir.81.6.1860. [DOI] [PubMed] [Google Scholar]
  12. Floras J., Vann Jones J., Hassan M. O., Osikowska B. A., Sever P. S., Sleight P. Failure of plasma norepinephrine to consistently reflect sympathetic activity in humans. Hypertension. 1986 Aug;8(8):641–649. doi: 10.1161/01.hyp.8.8.641. [DOI] [PubMed] [Google Scholar]
  13. Hainsworth R. Reflexes from the heart. Physiol Rev. 1991 Jul;71(3):617–658. doi: 10.1152/physrev.1991.71.3.617. [DOI] [PubMed] [Google Scholar]
  14. Hasking G. J., Esler M. D., Jennings G. L., Burton D., Johns J. A., Korner P. I. Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity. Circulation. 1986 Apr;73(4):615–621. doi: 10.1161/01.cir.73.4.615. [DOI] [PubMed] [Google Scholar]
  15. Ikram H., Fitzpatrick D. Double-blind trial of chronic oral beta blockade in congestive cardiomyopathy. Lancet. 1981 Sep 5;2(8245):490–493. doi: 10.1016/s0140-6736(81)90881-3. [DOI] [PubMed] [Google Scholar]
  16. Kaye D. M., Lambert G. W., Lefkovits J., Morris M., Jennings G., Esler M. D. Neurochemical evidence of cardiac sympathetic activation and increased central nervous system norepinephrine turnover in severe congestive heart failure. J Am Coll Cardiol. 1994 Mar 1;23(3):570–578. doi: 10.1016/0735-1097(94)90738-2. [DOI] [PubMed] [Google Scholar]
  17. Mann D. L., Kent R. L., Parsons B., Cooper G., 4th Adrenergic effects on the biology of the adult mammalian cardiocyte. Circulation. 1992 Feb;85(2):790–804. doi: 10.1161/01.cir.85.2.790. [DOI] [PubMed] [Google Scholar]
  18. Nakamura M., Funakoshi T., Yoshida H., Arakawa N., Suzuki T., Hiramori K. Endothelium-dependent vasodilation is augmented by angiotensin converting enzyme inhibitors in healthy volunteers. J Cardiovasc Pharmacol. 1992 Dec;20(6):949–954. doi: 10.1097/00005344-199212000-00015. [DOI] [PubMed] [Google Scholar]
  19. Sundlöf G., Wallin B. G. The variability of muscle nerve sympathetic activity in resting recumbent man. J Physiol. 1977 Nov;272(2):383–397. doi: 10.1113/jphysiol.1977.sp012050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Waagstein F., Bristow M. R., Swedberg K., Camerini F., Fowler M. B., Silver M. A., Gilbert E. M., Johnson M. R., Goss F. G., Hjalmarson A. Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Metoprolol in Dilated Cardiomyopathy (MDC) Trial Study Group. Lancet. 1993 Dec 11;342(8885):1441–1446. doi: 10.1016/0140-6736(93)92930-r. [DOI] [PubMed] [Google Scholar]
  21. Waagstein F., Caidahl K., Wallentin I., Bergh C. H., Hjalmarson A. Long-term beta-blockade in dilated cardiomyopathy. Effects of short- and long-term metoprolol treatment followed by withdrawal and readministration of metoprolol. Circulation. 1989 Sep;80(3):551–563. doi: 10.1161/01.cir.80.3.551. [DOI] [PubMed] [Google Scholar]
  22. Waagstein F., Hjalmarson A., Varnauskas E., Wallentin I. Effect of chronic beta-adrenergic receptor blockade in congestive cardiomyopathy. Br Heart J. 1975 Oct;37(10):1022–1036. doi: 10.1136/hrt.37.10.1022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wallin B. G., Esler M., Dorward P., Eisenhofer G., Ferrier C., Westerman R., Jennings G. Simultaneous measurements of cardiac noradrenaline spillover and sympathetic outflow to skeletal muscle in humans. J Physiol. 1992;453:45–58. doi: 10.1113/jphysiol.1992.sp019217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wallin B. G., Sundlöf G., Strömgren E., Aberg H. Sympathetic outflow to muscles during treatment of hypertension with metoprolol. Hypertension. 1984 Jul-Aug;6(4):557–562. doi: 10.1161/01.hyp.6.4.557. [DOI] [PubMed] [Google Scholar]
  25. Woodley S. L., Gilbert E. M., Anderson J. L., O'Connell J. B., Deitchman D., Yanowitz F. G., Mealey P. C., Volkman K., Renlund D. G., Menlove R. Beta-blockade with bucindolol in heart failure caused by ischemic versus idiopathic dilated cardiomyopathy. Circulation. 1991 Dec;84(6):2426–2441. doi: 10.1161/01.cir.84.6.2426. [DOI] [PubMed] [Google Scholar]

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