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Cardiac Sympathetic Activity in Myocardial Ischemia: Release and Effects of Noradrenaline

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Adrenergic Mechanisms in Myocardial Ischemia

Summary

Sympathetic overactivity in myocardial ischemia is closely associated with the progression of myocyte injury and the incidence of malignant arrhythmias. Adrenergic stimulation of the ischemic myocardium is predominantly due to increased local noradrenaline concentrations in the heart, whereas plasma catecholamine levels are of minor relevance. During the first few minutes of ischemia, efferent sympathetic nerves are activated. Excessive accumulation of noradrenaline, however, is prevented since adenosine, formed in the ischemic myocardium, suppresses exocytotic noradrenaline release, and released noradrenaline is rapidly removed as long as catecholamine reuptake is functional.

With progression of ischemia to more than 10min, the myocardium is no longer protected against excess catecholamine accumulation in the interstitial space, since local metabolic release mechanisms become increasingly important. This release, which is independent of central sympathetic activity and from extracellular calcium, occurs in two steps: First, noradrenaline escapes from its intracellular storage vesicles and accumulates in the cytoplasm of the neuron. In a second, rate-limiting step, noradrenaline is transported across the plasma membrane into the interstitial space, using the neuronal uptake carrier in reverse of its normal transport direction. As a consequence of local metabolic catecholamine release, extracellular noradrenaline reaches 1000 times the normal plasma concentration within 20min of ischemia.

Studies using acute and chronic sympathetic denervation and antiadrenergic agents demonstrate that local metabolic, rather than centrally induced noradrenaline release is critically involved in the progression of ischemie cell damage within the occurrence of ventricular fibrillation in early ischemia.

Myocardial ischemia results in a temporary supersensitivity of the myocytes to catecholamines. This is due to a twofold increase of α1- and a 30% increase of β-adrenergic receptor number at the cell surface. The sensitization of adenylate cyclase during the first 20 min of total ischemia is followed by a rapid inactivation of the enzyme. The β-adrenergic hyperresponsiveness to catecholamines is therefore limited to the first few minutes of ischemia.

The deleterious combination of extremely high noradrenaline concentrations with a temporarily enhanced responsiveness to catecholamines of the tissue is thought to accelerate the propagation of the wavefront of irreversible cell damage within the ischemie myocardium. Moreover, the inhomogenous distribution of catecholamine excess within the heart is considered to promote malignant arrhythmias by unmasking and enhancing electrophysiological disturbances in early ischemia.

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  1. Department of Cardiology, University of Heidelberg, Heidelberg, Germany

    Prof. Dr. A. Schömig & G. Richardt

  2. Department of Cardiology, Bergheimer Straße 58, 6900, Heidelberg, Germany

    Prof. Dr. A. Schömig

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  1. Prof. Dr. A. Schömig
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  2. G. Richardt
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Gerd Heusch John Ross Jr.

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Schömig, A., Richardt, G. (1991). Cardiac Sympathetic Activity in Myocardial Ischemia: Release and Effects of Noradrenaline. In: Heusch, G., Ross, J. (eds) Adrenergic Mechanisms in Myocardial Ischemia. Steinkopff, Heidelberg. https://doi.org/10.1007/978-3-662-11038-6_2

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  • DOI: https://doi.org/10.1007/978-3-662-11038-6_2

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  • Print ISBN: 978-3-662-11040-9

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