This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Patel, M. B. Articles by Hintze, T. H. Search for Related Content PubMed PubMed Citation Articles by Patel, M. B. Articles by Hintze, T. H.

Circulation, Vol 84, 2091-2100, Copyright © 1991 by American Heart Association

ARTICLES

Altered function and structure of the heart in dogs with chronic elevation in plasma norepinephrine

MB Patel, JM Stewart, AV Loud, P Anversa, J Wang, L Fiegel and TH Hintze
Department of Physiology, New York Medical College, Valhalla 10595.

BACKGROUND. We have previously shown that chronic elevation of plasma norepinephrine leads to a functional independent increase in left ventricular weight. The goals of the present study were to determine quantitatively the component of the myocardium that accounted for the observed structural changes and to determine the function of the hypertrophied myocardium. METHODS AND RESULTS. Mongrel dogs were chronically instrumented for measurement of arterial and left ventricular pressures, left ventricular internal diameter, and left ventricular wall thickness. Subcutaneous osmotic pumps were implanted to release norepinephrine continuously for 28 days. Hemodynamics were measured with dogs in the quietly resting state and during infusions of isoproterenol at 0.1 and 0.5 micrograms/kg/min before and on days 14 and 28 during the infusion of norepinephrine. The hemodynamic response to 10 micrograms/kg phenylephrine, given as a bolus, was also assessed before norepinephrine and 28 days during the infusion of norepinephrine, and the end-systolic pressure-diameter or wall-stress- diameter relations were calculated. On day 28, hearts were arrested in diastole and perfusion fixed in situ. Tissue samples were prepared for electron microscopy and morphometry. Hemodynamic studies showed that isoproterenol (0.5 micrograms/kg/min) reduced mean arterial pressure (MAP) to the same point on each experimental day, and the increases in indexes of contractility were reduced during norepinephrine infusion. Left ventricular dP/dtmax increased 131 +/- 24% on control day, only 67 +/- 20% on day 14, and 55 +/- 18% on day 28. Similar changes were observed in dP/dt/DP40 and dP/dt/end-diastolic circumference. However, Emax, the slope of the end-systolic pressure-diameter or wall stress diameter relations, was unchanged, suggesting that inotropic state was not altered. Morphometric studies showed that the cross-sectional area of myocytes increased by 55%, but myocyte and capillary densities decreased by 34% and 29%, respectively (p less than 0.05) in dogs with high norepinephrine levels. There were no differences in volume fractions of myocytes, capillary lumen, or interstitium or capillary-to- myocyte ratio. CONCLUSIONS. The myocardium of dogs with high norepinephrine levels shows reduced inotropic response to beta- adrenergic stimulation despite the increases in left ventricular mass and left ventricular wall thickness, which are a result of growth of the cardiac myocytes and characteristic of concentric hypertrophy. These data suggest that chronic adrenergic stimulation of the heart reduces the beta-receptor coupling to the contractile response without importantly compromising left ventricular function.

This article has been cited by other articles:

				R. Yang and L. A. Barouch Leptin Signaling and Obesity: Cardiovascular Consequences Circ. Res., September 14, 2007; 101(6): 545 - 559. [Abstract] [Full Text] [PDF]

				D. R. Seals and F. A. Dinenno Collateral damage: cardiovascular consequences of chronic sympathetic activation with human aging Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H1895 - H1905. [Abstract] [Full Text] [PDF]

				L. A. Nikolaidis, D. Trumble, T. Hentosz, A. Doverspike, R. Huerbin, M. A. Mathier, Y.-T. Shen, and R. P. Shannon Catecholamines restore myocardial contractility in dilated cardiomyopathy at the expense of increased coronary blood flow and myocardial oxygen consumption (MvO2 cost of catecholamines in heart failure) Eur J Heart Fail, June 1, 2004; 6(4): 409 - 419. [Abstract] [Full Text] [PDF]

				M. P. Schlaich, D. M. Kaye, E. Lambert, M. Sommerville, F. Socratous, and M. D. Esler Relation Between Cardiac Sympathetic Activity and Hypertensive Left Ventricular Hypertrophy Circulation, August 5, 2003; 108(5): 560 - 565. [Abstract] [Full Text] [PDF]

				A. Sherwood, E. C. D. Gullette, A. L. Hinderliter, A. Georgiades, M. Babyak, R. A. Waugh, and J. A. Blumenthal Relationship of Clinic, Ambulatory, and Laboratory Stress Blood Pressure to Left Ventricular Mass in Overweight Men and Women With High Blood Pressure Psychosom Med, March 1, 2002; 64(2): 247 - 257. [Abstract] [Full Text]

				F. Leon-Velarde, M.-C. Bourin, R. Germack, K. Mohammadi, B. Crozatier, and J.-P. Richalet Differential alterations in cardiac adrenergic signaling in chronic hypoxia or norepinephrine infusion Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2001; 280(1): R274 - R281. [Abstract] [Full Text] [PDF]

				T. W. Kamarck, J. Eranen, J. R. Jennings, S. B. Manuck, S. A. Everson, G. A. Kaplan, and J. T. Salonen Anticipatory Blood Pressure Responses to Exercise Are Associated With Left Ventricular Mass in Finnish Men : Kuopio Ischemic Heart Disease Risk Factor Study Circulation, September 19, 2000; 102(12): 1394 - 1399. [Abstract] [Full Text] [PDF]

				H. Yonemochi, S. Yasunaga, Y. Teshima, N. Takahashi, M. Nakagawa, M. Ito, and T. Saikawa Rapid Electrical Stimulation of Contraction Reduces the Density of {beta}-Adrenergic Receptors and Responsiveness of Cultured Neonatal Rat Cardiomyocytes : Possible Involvement of Microtubule Disassembly Secondary to Mechanical Stress Circulation, June 6, 2000; 101(22): 2625 - 2630. [Abstract] [Full Text] [PDF]

				M. White, R. J. Wiechmann, R. L. Roden, M. B. Hagan, M. M. Wollmering, J. D. Port, E. Hammond, W. T. Abraham, E. E. Wolfel, J. Lindenfeld, et al. Cardiac ß-Adrenergic Neuroeffector Systems in Acute Myocardial Dysfunction Related to Brain Injury : Evidence for Catecholamine-Mediated Myocardial Damage Circulation, October 15, 1995; 92(8): 2183 - 2189. [Abstract] [Full Text]

				J. Kajstura, X. Zhang, Y. Liu, E. Szoke, W. Cheng, G. Olivetti, T. H. Hintze, and P. Anversa The Cellular Basis of Pacing-Induced Dilated Cardiomyopathy : Myocyte Cell Loss and Myocyte Cellular Reactive Hypertrophy Circulation, October 15, 1995; 92(8): 2306 - 2317. [Abstract] [Full Text]