Effects of cardiac denervation on development of heart failure and catecholamine desensitization

Naoki Sato, Stephen Vatner, You Tang Shen, Raymond K. Kudej, Bijan Ghaleh-Marzban, Masami Uechi, Kuniya Asai, Israel Mirsky, Thomas A. Patrick, Richard P. Shannon, Dorothy Vatner

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Two signatures of heart failure are activation of the sympathetic nervous system and catecholamine desensitization. However, whether or not the elimination of cardiac nerves affects either the progression of heart failure or catecholamine desensitization is not clear. Methods and Results: We studied 8 dogs with selective ventricular denervation (VD) (surgical technique) and 10 intact dogs, chronically instrumented for measurement of left ventricular (LV) and arterial pressures, LV dP/dt, LV internal diameter, and wall thickness before and after heart failure was induced by rapid pacing (240 bpm) for 3 to 4 weeks. VD was confirmed by the absence of reflex effects induced by intracardiac veratrine and depiction of tissue norepinephrine and by supersensitive responses to norepinephrine. During the development of heart failure, LV end-systolic and end-diastolic stresses and heart rate increased, while myocardial contractility, as reflected by LV dP/dt and mean velocity of circumferential fiber shortening corrected for heart rate (Vcf(c)), decreased in both intact and VD dogs. However, the increases in LV end-diastolic stress and decreases in LV dP/dt as well as the relationship between LV systolic stress and Vcf(c) in heart failure were less (P<.05) in VD dogs. The responses of LV dP/dt and heart rate to both isoproterenol and norepinephrine in intact dogs were reduced in heart failure. The physiological desensitization to the inotropic effects of isoproterenol and norepinephrine was less in dogs with VD (P<.05), but chronotropic responses were similar because atrial innervation remained intact. Plasma norepinephrine levels were not different in VD dogs (592±79 pg/mL) compared with intact dogs (576±81 pg/mL) in heart failure. Conclusions: Dogs with selective VD tolerated the development of heart failure better than intact dogs and demonstrated significantly less catecholamine desensitization. The latter indicates that intact ventricular innervation is required for physiological expression of catecholamine desensitization despite comparable elevation of plasma catecholamines during the development of heart failure.

Original languageEnglish (US)
Pages (from-to)2130-2140
Number of pages11
JournalCirculation
Volume95
Issue number8
DOIs
StatePublished - Apr 15 1997

Fingerprint

Denervation
Catecholamines
Heart Failure
Dogs
Norepinephrine
Heart Rate
Isoproterenol
Veratrine
Psychologic Desensitization
Sympathetic Nervous System
Ventricular Pressure
Reflex
Arterial Pressure

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Keywords

  • catecholamines
  • heart failure
  • physiology
  • receptors, beta, adrenergic
  • ventricular denervation

Cite this

Sato, Naoki ; Vatner, Stephen ; Shen, You Tang ; Kudej, Raymond K. ; Ghaleh-Marzban, Bijan ; Uechi, Masami ; Asai, Kuniya ; Mirsky, Israel ; Patrick, Thomas A. ; Shannon, Richard P. ; Vatner, Dorothy. / Effects of cardiac denervation on development of heart failure and catecholamine desensitization. In: Circulation. 1997 ; Vol. 95, No. 8. pp. 2130-2140.
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abstract = "Background: Two signatures of heart failure are activation of the sympathetic nervous system and catecholamine desensitization. However, whether or not the elimination of cardiac nerves affects either the progression of heart failure or catecholamine desensitization is not clear. Methods and Results: We studied 8 dogs with selective ventricular denervation (VD) (surgical technique) and 10 intact dogs, chronically instrumented for measurement of left ventricular (LV) and arterial pressures, LV dP/dt, LV internal diameter, and wall thickness before and after heart failure was induced by rapid pacing (240 bpm) for 3 to 4 weeks. VD was confirmed by the absence of reflex effects induced by intracardiac veratrine and depiction of tissue norepinephrine and by supersensitive responses to norepinephrine. During the development of heart failure, LV end-systolic and end-diastolic stresses and heart rate increased, while myocardial contractility, as reflected by LV dP/dt and mean velocity of circumferential fiber shortening corrected for heart rate (Vcf(c)), decreased in both intact and VD dogs. However, the increases in LV end-diastolic stress and decreases in LV dP/dt as well as the relationship between LV systolic stress and Vcf(c) in heart failure were less (P<.05) in VD dogs. The responses of LV dP/dt and heart rate to both isoproterenol and norepinephrine in intact dogs were reduced in heart failure. The physiological desensitization to the inotropic effects of isoproterenol and norepinephrine was less in dogs with VD (P<.05), but chronotropic responses were similar because atrial innervation remained intact. Plasma norepinephrine levels were not different in VD dogs (592±79 pg/mL) compared with intact dogs (576±81 pg/mL) in heart failure. Conclusions: Dogs with selective VD tolerated the development of heart failure better than intact dogs and demonstrated significantly less catecholamine desensitization. The latter indicates that intact ventricular innervation is required for physiological expression of catecholamine desensitization despite comparable elevation of plasma catecholamines during the development of heart failure.",
keywords = "catecholamines, heart failure, physiology, receptors, beta, adrenergic, ventricular denervation",
author = "Naoki Sato and Stephen Vatner and Shen, {You Tang} and Kudej, {Raymond K.} and Bijan Ghaleh-Marzban and Masami Uechi and Kuniya Asai and Israel Mirsky and Patrick, {Thomas A.} and Shannon, {Richard P.} and Dorothy Vatner",
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Sato, N, Vatner, S, Shen, YT, Kudej, RK, Ghaleh-Marzban, B, Uechi, M, Asai, K, Mirsky, I, Patrick, TA, Shannon, RP & Vatner, D 1997, 'Effects of cardiac denervation on development of heart failure and catecholamine desensitization', Circulation, vol. 95, no. 8, pp. 2130-2140. https://doi.org/10.1161/01.CIR.95.8.2130

Effects of cardiac denervation on development of heart failure and catecholamine desensitization. / Sato, Naoki; Vatner, Stephen; Shen, You Tang; Kudej, Raymond K.; Ghaleh-Marzban, Bijan; Uechi, Masami; Asai, Kuniya; Mirsky, Israel; Patrick, Thomas A.; Shannon, Richard P.; Vatner, Dorothy.

In: Circulation, Vol. 95, No. 8, 15.04.1997, p. 2130-2140.

Research output: Contribution to journalArticle

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T1 - Effects of cardiac denervation on development of heart failure and catecholamine desensitization

AU - Sato, Naoki

AU - Vatner, Stephen

AU - Shen, You Tang

AU - Kudej, Raymond K.

AU - Ghaleh-Marzban, Bijan

AU - Uechi, Masami

AU - Asai, Kuniya

AU - Mirsky, Israel

AU - Patrick, Thomas A.

AU - Shannon, Richard P.

AU - Vatner, Dorothy

PY - 1997/4/15

Y1 - 1997/4/15

N2 - Background: Two signatures of heart failure are activation of the sympathetic nervous system and catecholamine desensitization. However, whether or not the elimination of cardiac nerves affects either the progression of heart failure or catecholamine desensitization is not clear. Methods and Results: We studied 8 dogs with selective ventricular denervation (VD) (surgical technique) and 10 intact dogs, chronically instrumented for measurement of left ventricular (LV) and arterial pressures, LV dP/dt, LV internal diameter, and wall thickness before and after heart failure was induced by rapid pacing (240 bpm) for 3 to 4 weeks. VD was confirmed by the absence of reflex effects induced by intracardiac veratrine and depiction of tissue norepinephrine and by supersensitive responses to norepinephrine. During the development of heart failure, LV end-systolic and end-diastolic stresses and heart rate increased, while myocardial contractility, as reflected by LV dP/dt and mean velocity of circumferential fiber shortening corrected for heart rate (Vcf(c)), decreased in both intact and VD dogs. However, the increases in LV end-diastolic stress and decreases in LV dP/dt as well as the relationship between LV systolic stress and Vcf(c) in heart failure were less (P<.05) in VD dogs. The responses of LV dP/dt and heart rate to both isoproterenol and norepinephrine in intact dogs were reduced in heart failure. The physiological desensitization to the inotropic effects of isoproterenol and norepinephrine was less in dogs with VD (P<.05), but chronotropic responses were similar because atrial innervation remained intact. Plasma norepinephrine levels were not different in VD dogs (592±79 pg/mL) compared with intact dogs (576±81 pg/mL) in heart failure. Conclusions: Dogs with selective VD tolerated the development of heart failure better than intact dogs and demonstrated significantly less catecholamine desensitization. The latter indicates that intact ventricular innervation is required for physiological expression of catecholamine desensitization despite comparable elevation of plasma catecholamines during the development of heart failure.

AB - Background: Two signatures of heart failure are activation of the sympathetic nervous system and catecholamine desensitization. However, whether or not the elimination of cardiac nerves affects either the progression of heart failure or catecholamine desensitization is not clear. Methods and Results: We studied 8 dogs with selective ventricular denervation (VD) (surgical technique) and 10 intact dogs, chronically instrumented for measurement of left ventricular (LV) and arterial pressures, LV dP/dt, LV internal diameter, and wall thickness before and after heart failure was induced by rapid pacing (240 bpm) for 3 to 4 weeks. VD was confirmed by the absence of reflex effects induced by intracardiac veratrine and depiction of tissue norepinephrine and by supersensitive responses to norepinephrine. During the development of heart failure, LV end-systolic and end-diastolic stresses and heart rate increased, while myocardial contractility, as reflected by LV dP/dt and mean velocity of circumferential fiber shortening corrected for heart rate (Vcf(c)), decreased in both intact and VD dogs. However, the increases in LV end-diastolic stress and decreases in LV dP/dt as well as the relationship between LV systolic stress and Vcf(c) in heart failure were less (P<.05) in VD dogs. The responses of LV dP/dt and heart rate to both isoproterenol and norepinephrine in intact dogs were reduced in heart failure. The physiological desensitization to the inotropic effects of isoproterenol and norepinephrine was less in dogs with VD (P<.05), but chronotropic responses were similar because atrial innervation remained intact. Plasma norepinephrine levels were not different in VD dogs (592±79 pg/mL) compared with intact dogs (576±81 pg/mL) in heart failure. Conclusions: Dogs with selective VD tolerated the development of heart failure better than intact dogs and demonstrated significantly less catecholamine desensitization. The latter indicates that intact ventricular innervation is required for physiological expression of catecholamine desensitization despite comparable elevation of plasma catecholamines during the development of heart failure.

KW - catecholamines

KW - heart failure

KW - physiology

KW - receptors, beta, adrenergic

KW - ventricular denervation

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