STATE-OF-THE-ART PAPER
The Sympathetic Nervous System in Heart FailurePhysiology, Pathophysiology, and Clinical Implications
Filippos Triposkiadis, MD*,
George Karayannis, MD*,
Grigorios Giamouzis, MD*, ,
John Skoularigis, MD*,
George Louridas, MD and
Javed Butler, MD, MPH,*
* Department of Cardiology, Larissa University Hospital, Larissa, Greece
Department of Cardiology, AHEPA University Hospital, Thessaloniki, Greece
Cardiology Division, Emory University, Atlanta, Georgia
Manuscript received February 24, 2009;
revised manuscript received May 11, 2009,
accepted May 14, 2009.
* Reprint requests and correspondence: Dr. Javed Butler, Emory University Hospital, 1365 Clifton Road, NE, Suite AT430, Atlanta, Georgia 30322 (Email: javed.butler{at}emory.edu).
Heart failure is a syndrome characterized initially by left ventricular dysfunction that triggers countermeasures aimed to restore cardiac output. These responses are compensatory at first but eventually become part of the disease process itself leading to further worsening cardiac function. Among these responses is the activation of the sympathetic nervous system (SNS) that provides inotropic support to the failing heart increasing stroke volume, and peripheral vasoconstriction to maintain mean arterial perfusion pressure, but eventually accelerates disease progression affecting survival. Activation of SNS has been attributed to withdrawal of normal restraining influences and enhancement of excitatory inputs including changes in: 1) peripheral baroreceptor and chemoreceptor reflexes; 2) chemical mediators that control sympathetic outflow; and 3) central integratory sites. The interface between the sympathetic fibers and the cardiovascular system is formed by the adrenergic receptors (ARs). Dysregulation of cardiac beta1-AR signaling and transduction are key features of heart failure progression. In contrast, cardiac beta2-ARs and alpha1-ARs may function in a compensatory fashion to maintain cardiac inotropy. Adrenergic receptor polymorphisms may have an impact on the adaptive mechanisms, susceptibilities, and pharmacological responses of SNS. The beta-AR blockers and the inhibitors of the renin-angiotensin-aldosterone axis form the mainstay of current medical management of chronic heart failure. Conversely, central sympatholytics have proved harmful, whereas sympathomimetic inotropes are still used in selected patients with hemodynamic instability. This review summarizes the changes in SNS in heart failure and examines how modulation of SNS activity may affect morbidity and mortality from this syndrome.
Key Words: heart failure • sympathetic nervous system • adrenergic receptor • beta-blockers • sympatholytics • sympathomimetic inotropes
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Abbreviations and Acronyms
| | AR = adrenergic receptor | | ATP = adenosine triphosphate | | cAMP = 3',5'-cyclic monophosphate | | EPI = epinephrine | | MIBG = metaiodobenzylguanidine | | NE = norepinephrine | | SNS = sympathetic nervous system |
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