Sensory Nerves pp 185-225 | Cite as

Regulation of Cardiac Afferent Excitability in Ischemia

  • Liang-Wu Fu
  • John C. LonghurstEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 194)


The heart at the time of Sir William Harvey originally was thought to be an insensate organ. Today, however, we know that this organ is innervated by sensory nerves that course centrally though mixed nerve pathways that also contain parasympathetic or sympathetic motor nerves. Angina or cardiac pain is now well recognized as a pressure-like pain that occurs during myocardial ischemia when coronary artery blood flow is interrupted. Sympathetic (or spinal) afferent fibers that are either finely myelinated or unmyelinated are responsible for the transmission of information to the brain that ultimately allows the perception of angina as well as activation of the sympathetic nervous system, resulting in tachycardia, hypertension, and sometimes arrhythmias. Although early studies defined the importance of the vagal and sympathetic cardiac afferent systems in reflex autonomic control, until recently there has been little appreciation of the mechanisms of activation of the sensory endings. This review examines the role of a number of chemical mediators and their sources that are activated by the ischemic process. In this regard, patients with ischemic syndromes, particularly myocardial infarction and unstable angina, are known to have platelet activation, which leads to release of a number of chemical mediators, including serotonin, histamine, and thromboxane A2, all of which stimulate ischemically sensitive cardiac spinal afferent endings in the ventricles through specific receptor-mediated processes. Furthermore, protons from lactic acid, bradykinin, and reactive oxygen species, especially hydroxyl radicals, individually and frequently in combination, stimulate these endings during ischemia. Cyclooxygenase products appear to sensitize the endings to the action of bradykinin and histamine. These studies of the chemical mechanisms of activation of cardiac sympathetic afferent endings during ischemia have the potential to provide targeted therapies that can modify the angina and the deleterious reflex responses that have the potential to exacerbate ischemia and myocardial cell death.


Sympathetic nervous system Cardiac spinal afferent Myocardial ischemia Ischemic mediator Nociceptor 



This work was supported, in part, by National Heart, Lung, and Blood Institute grant HL-66217. J.C.L holds the Larry K. Dodge Chair in Integrative Biology and the Susan Samueli Chair in Integrative Medicine.


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© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Department of Medicine, Department of Physiology and Biophysics, Susan Samueli Center for Integrative Medicine, School of Medicine, C240 Medical Sciences IUniversity of CaliforniaIrvineUSA

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