Copyright © 1991 by the European Society of Cardiology.
© 1991 The European Society of Cardiology
Catecholamine release and arrhythmias in acute myocardial ischaemia
Department of Cardiology, University of Heidelberg Heidelberg, Germany
Correspondence: Prof. Dr. Albert Schömig, Department of Cardiology, University of Heidelberg, Bergheimer Str. 58, D-6900 Heidelberg, Germany.
Increased sympathetic activity is assumed to contribute substantially to the occurrence of malignant arrhythmias in patients with coronary heart disease, since the rate of sudden cardiac death is significantly reduced by β-adrenoceptor blockade, but not by antiarrhythmic agents such as flecainide or encainide.
During acute myocardial ischaemia, adrenergic stimulation of the ischaemic myocardium is independent of plasma catecholamines. Rather, it is caused by the combination of excessively high local noradrenaline concentrations and an enhanced responsiveness of the myocyte to catecholamines. Myocardial ischaemia of 15min duration results in a 100-fold increase in catecholamine concentrations within the extracellular space of the ischaemic zone, a two-fold increase in functionally coupled 
-adrenoceptors, and a 30% increase in β-adrenoccptors.
Within the first l0min of ischaemia, the myocardium is protected from excessive catecholamine release. Ischaemia-associated metabolic alterations, such as extracellular potassium accumulation, acidosis, and especially the accumulation of adenosine reduce the transmitter release caused by central sympathetic activation. Furthermore, the functional neuronal amine reuptake (uptake,) prevents excessive local accumulation of noradrenaline.
With progression of ischaemia to more than 10min, local nonexocytotic catecholamine release becomes predominant. This release is independent of central sympathetic nerve activity, availability of extracellular calcium, activation of both neuronal calcium channels and protein kinase C, and it is not accompanied by the release of sympathetic cotransmitters such as neuropeptide Y. It has been demonstrated to be nonexocytotic and to be caused by a carrier-mediated transport of noradrenaline from the sympathetic nerve ending into the synaptic cleft. This release is not modulated through presynaptic receptors. It is, however, suppressed by blockers of uptake, and by inhibitors of sodium-proton exchange.
Depletion of cardiac catecholamine stores by chronic surgical or chemical sympathectomy effectively suppresses malignant arrhythmias induced by experimental coronary ligature. Accordingly, inhibitors of nonexocytotic noradrenaline release, such as uptake, blocking agents or sodium-proton exchange inhibitors, effectively reduce the occurrence of ischaemia-associated ventricular fibrillation, emphasizing the relevance of nonexocytotic release mechanisms in myocardial ischaemia.
Key Words: Noradrenaline • myocardial ischaemia • ventricular arrhythmias • exocytosis • nonexocytotic release • sodium-proton exchange • uptake1 • neuropeptide Y.
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