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. 1985 Nov;76(5):1740–1747. doi: 10.1172/JCI112164

Tracer norepinephrine kinetics in coronary circulation of patients with heart failure secondary to chronic pressure and volume overload.

C P Rose, J H Burgess, D Cousineau
PMCID: PMC424198  PMID: 4056051

Abstract

Controversy exists over the nature of the abnormality in cardiac sympathetic nerves in heart failure. In the cardiomyopathy of the Syrian hamster, reduction in tissue stores and increased turnover of norepinephrine is clearly associated with excessive sympathetic stimulation but in animal models and humans with heart failure secondary to mechanical overload there is evidence for depression of neuronal uptake. Because norepinephrine is both released and taken up by sympathetic fibers it is impossible to assess norepinephrine kinetics in an intact heart without separating these two functions. A technique for doing so has recently been developed in normal dogs and we therefore acquired similar data in humans with heart failure secondary to chronic pressure and volume overload. The technique involves the combination of transient norepinephrine tracer coronary sinus outflow in relation to intravascular and interstitial references after simultaneous injection into the left coronary artery and the measurement of endogenous norepinephrine concentrations in artery and coronary sinus. We found a marked reduction in cardiac norepinephrine release and uptake in a group of patients with clinical left ventricular failure secondary to mechanical overload, relative to a group of patients with no failure. Norepinephrine balance and overflow across the heart were not significantly different. We conclude that there is hypofunction of the cardiac sympathetic nerves in heart failure secondary to mechanical overload and that traditional methods are inadequate in assessing cardiac norepinephrine kinetics when there are simultaneous changes in neuronal uptake and release.

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Selected References

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

  1. Borchard F. The adrenergic nerves of the normal and the hypertrophied heart. Norm Pathol Anat (Stuttg) 1978;33:1–68. [PubMed] [Google Scholar]
  2. Bristow M. R., Ginsburg R., Minobe W., Cubicciotti R. S., Sageman W. S., Lurie K., Billingham M. E., Harrison D. C., Stinson E. B. Decreased catecholamine sensitivity and beta-adrenergic-receptor density in failing human hearts. N Engl J Med. 1982 Jul 22;307(4):205–211. doi: 10.1056/NEJM198207223070401. [DOI] [PubMed] [Google Scholar]
  3. CHIDSEY C. A., BRAUNWALD E., MORROW A. G., MASON D. T. MYOCARDIAL NOREPINEPHRINE CONCENTRATION IN MAN. EFFECTS OF RESERPINE AND OF CONGESTIVE HEART FAILURE. N Engl J Med. 1963 Sep 26;269:653–658. doi: 10.1056/NEJM196309262691302. [DOI] [PubMed] [Google Scholar]
  4. CHIDSEY C. A., HARRISON D. C., BRAUNWALD E. Release of norepinephrine from the heart by vasoactive amines. Proc Soc Exp Biol Med. 1962 Mar;109:488–490. doi: 10.3181/00379727-109-27244. [DOI] [PubMed] [Google Scholar]
  5. Chidsey C. A., Sonnenblick E. H., Morrow A. G., Braunwald E. Norepinephrine stores and contractile force of papillary muscle from the failing human heart. Circulation. 1966 Jan;33(1):43–51. doi: 10.1161/01.cir.33.1.43. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Cousineau D., Goresky C. A., Bach G. G., Rose C. P. Effect of beta-adrenergic blockade on in vivo norepinephrine release in canine heart. Am J Physiol. 1984 Feb;246(2 Pt 2):H283–H292. doi: 10.1152/ajpheart.1984.246.2.H283. [DOI] [PubMed] [Google Scholar]
  8. Cousineau D., Rose C. P., Goresky C. A. In vivo characterization of the adrenergic receptors in the working canine heart. Circ Res. 1981 Aug;49(2):501–510. doi: 10.1161/01.res.49.2.501. [DOI] [PubMed] [Google Scholar]
  9. Cousineau D., Rose C. P., Goresky C. A. Labeled catecholamine uptake in the dog heart. Interactions between capillary wall and sympathetic nerve uptake. Circ Res. 1980 Sep;47(3):329–338. doi: 10.1161/01.res.47.3.329. [DOI] [PubMed] [Google Scholar]
  10. Fischer J. E., Horst W. D., Kopin I. J. Norepinephrine metabolism in hypertrophied rat hearts. Nature. 1965 Aug 28;207(5000):951–953. doi: 10.1038/207951a0. [DOI] [PubMed] [Google Scholar]
  11. Fronek K. Evaluation of long-term chemical sympathectomy in adult rabbits. Am J Physiol. 1980 Apr;238(4):H527–H532. doi: 10.1152/ajpheart.1980.238.4.H527. [DOI] [PubMed] [Google Scholar]
  12. Fuster V., Danielson M. A., Robb R. A., Broadbent J. C., Brown A. L., Jr, Elveback L. R. Quantitation of left ventricular myocardial fiber hypertrophy and interstitial tissue in human hearts with chronically increased volume and pressure overload. Circulation. 1977 Mar;55(3):504–508. doi: 10.1161/01.cir.55.3.504. [DOI] [PubMed] [Google Scholar]
  13. Graefe K. H., Bönisch H., Trendelenburg U. Time-dependent changes in neuronal net uptake of noradrenaline after pretreatment with pargyline and-or reserpine. Naunyn Schmiedebergs Arch Pharmakol. 1971;271(1):1–28. doi: 10.1007/BF01002171. [DOI] [PubMed] [Google Scholar]
  14. Halter J. B., Kelley K. O., Gould K. L. Cardiac uptake and secretion of catecholamines during adrenergic stimulation in vivo. Am J Physiol. 1982 Jul;243(1):E52–E58. doi: 10.1152/ajpendo.1982.243.1.E52. [DOI] [PubMed] [Google Scholar]
  15. Krakoff L. R., Buccino R. A., Spann J. F., Jr, De Champlain J. Cardiac catechol O-methyltransferase and monoamine oxidase activity in congestive heart failure. Am J Physiol. 1968 Sep;215(3):549–552. doi: 10.1152/ajplegacy.1968.215.3.549. [DOI] [PubMed] [Google Scholar]
  16. Petch M. C., Nayler W. G. Uptake of catecholamines by human cardiac muscle in vitro. Br Heart J. 1979 Mar;41(3):336–339. doi: 10.1136/hrt.41.3.336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Peuler J. D., Johnson G. A. Simultaneous single isotope radioenzymatic assay of plasma norepinephrine, epinephrine and dopamine. Life Sci. 1977 Sep 1;21(5):625–636. doi: 10.1016/0024-3205(77)90070-4. [DOI] [PubMed] [Google Scholar]
  18. Rose C. P., Burgess J. H., Cousineau D. Reduced aortocoronary sinus extraction of epinephrine in patients with left ventricular failure secondary to long-term pressure or volume overload. Circulation. 1983 Aug;68(2):241–244. doi: 10.1161/01.cir.68.2.241. [DOI] [PubMed] [Google Scholar]
  19. Rose C. P., Goresky C. A., Bélanger P., Chen M. J. Effect of vasodilation and flow rate on capillary permeability surface product and interstitial space size in the coronary circulation. A frequency domain technique for modeling multiple dilution data with Laguerre functions. Circ Res. 1980 Sep;47(3):312–328. doi: 10.1161/01.res.47.3.312. [DOI] [PubMed] [Google Scholar]
  20. SPANN J. F., Jr, CHIDSEY C. A., BRAUNWALD E. REDUCTION OF CARDIAC STORES OF NOREPINEPHRINE IN EXPERIMENTAL HEART FAILURE. Science. 1964 Sep 25;145(3639):1439–1441. doi: 10.1126/science.145.3639.1439-a. [DOI] [PubMed] [Google Scholar]
  21. Schmid P. G., Lund D. D., Davis J. A., Whiteis C. A., Bhatnagar R. K., Roskoski R., Jr Selective sympathetic neural changes in hypertrophied right ventricle. Am J Physiol. 1982 Aug;243(2):H175–H180. doi: 10.1152/ajpheart.1982.243.2.H175. [DOI] [PubMed] [Google Scholar]
  22. Sole M. J., Kamble A. B., Hussain M. N. A possible change in the rate-limiting step for cardiac norepinephrine synthesis in the cardiomyopathic Syrian hamster. Circ Res. 1977 Dec;41(6):814–817. doi: 10.1161/01.res.41.6.814. [DOI] [PubMed] [Google Scholar]
  23. Sole M. J., Lo C. M., Laird C. W., Sonnenblick E. H., Wurtman R. J. Norepinephrine turnover in the heart and spleen of the cardiomyopathic Syrian hamster. Circ Res. 1975 Dec;37(6):855–862. doi: 10.1161/01.res.37.6.855. [DOI] [PubMed] [Google Scholar]
  24. Spann J. F., Jr, Chidsey C. A., Pool P. E., Braunwald E. Mechanism of norepinephrine depletion in experimental heart failure produced by aortic constriction in the guinea pig. Circ Res. 1965 Oct;17(4):312–321. doi: 10.1161/01.res.17.4.312. [DOI] [PubMed] [Google Scholar]
  25. Swedberg K., Hjalmarson A., Holmberg S. Effects of work and acute beta-receptor blockade on myocardial noradrenaline release in congestive cardiomyopathy. Clin Cardiol. 1979 Dec;2(6):424–430. doi: 10.1002/clc.4960020607. [DOI] [PubMed] [Google Scholar]
  26. Swedberg K., Viquerat C., Rouleau J. L., Roizen M., Atherton B., Parmley W. W., Chatterjee K. Comparison of myocardial catecholamine balance in chronic congestive heart failure and in angina pectoris without failure. Am J Cardiol. 1984 Oct 1;54(7):783–786. doi: 10.1016/s0002-9149(84)80208-8. [DOI] [PubMed] [Google Scholar]
  27. Vogel J. H., Jacobowitz D., Chidsey C. A. Distrubution of norepinephrine in the failing bovine heart. Correlation of chemical analysis and fluorescene microscopy. Circ Res. 1969 Jan;24(1):71–84. doi: 10.1161/01.res.24.1.71. [DOI] [PubMed] [Google Scholar]

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