(Circulation. 2001;103:691.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Cellular Mechanisms of Depressed Atrial Contractility in Patients With Chronic Atrial Fibrillation
From the Cardiovascular Research Institute Maastricht (U.S., J.A., M.A.A.), University of Maastricht, Maastricht, the Netherlands, and the Departments of Cardiology (C.S., I.S., M.V., D.F., P.H.) and Thoracic and Cardiovascular Surgery (F.S.), University Hospital Aachen, Aachen, Germany.
Correspondence to Dr Ulrich Schotten, Department of Physiology, Cardiovascular Research Institute Maastricht, University of Maastricht, PO Box 616, 6200 MD Maastricht, Netherlands. E-mail Schotten{at}fys.unimaas.nl
Background—After cardioversion of atrial fibrillation (AF), the contractile function of the atria is temporarily impaired. Although this has significant clinical implications, the underlying cellular mechanisms are poorly understood.
Methods and
Results—Forty-nine consecutive patients
submitted for mitral valve surgery were investigated. Twenty-three were
in persistent AF (
3 months); the others were in sinus rhythm. Before
extracorporal circulation, the right atrial appendage was excised.
ß-Adrenoceptors were quantified by radioligand binding, and G
proteins were quantified by Western blot analysis. The isometric
contractile response to Ca2+, isoproterenol,
Bay K8644, and the postrest potentiation of contractile force were
investigated in thin atrial trabeculae, which were also examined
histologically. The contractile force of the atrial preparations
obtained from AF patients was 75% less than that in preparations from
patients in sinus rhythm. Also, the positive inotropic effect of
isoproterenol was impaired, and Bay K8644 failed to increase atrial
contractile force. In contrast, the response to extracellular
Ca2+ was maintained, and the postrest
potentiation was preserved. ß-Adrenoceptor density and G-protein
expression were unchanged. Histological examination revealed 14% more
myolysis in the atria of AF patients.
Conclusions—After prolonged AF, atrial contractility was reduced by 75%. The impairment of ß-adrenergic modulation of contractile force cannot be explained by downregulation of ß-adrenoceptors or changes in G proteins. Dysfunction of the sarcoplasmic reticulum does not occur after prolonged AF. Failure of Bay K8644 to restore contractility suggests that the L-type Ca2+ channel is responsible for the contractile dysfunction. The restoration of contractile force by high extracellular Ca2+ shows that the contractile apparatus itself is nearly completely preserved after prolonged AF.
Key Words: arrhythmia • contractility • receptors, adrenergic, beta • remodeling • signal transduction.
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