Atrial fibrillation-induced atrial contractile dysfunction: A tachycardiomyopathy of a different sort

Abstract

Objective: Although AF-induced atrial contractile dysfunction has significant clinical implications the underlying intracellular mechanisms are poorly understood. Methods: From the right atrial appendages of 59 consecutive patients undergoing mitral valve surgery (31 in SR, 28 in chronic AF) thin muscle preparations (diameter<0.7 mm) were isolated. Isometric force of contraction was measured in the presence of different concentrations of Ca2+ and isoprenaline. To assess the function of the sarcoplasmic reticulum, the force-frequency relationship and the post-rest potentiation were studied. The myocardial density of the ryanodine-sensitive calcium release channel (CRC) of the sarcoplasmic reticulum was determined by [3H]ryanodine binding. Myocardial content of SR-Ca2+-ATPase (SERCA), phospholamban (Plb), calsequestrin (Cals) and the Na+/Ca2+-exchanger (NCX) were analyzed by Western blot analysis. Adenylyl cyclase activity was measured with a radiolabeled bioassay using [32P]ATP as a tracer. Results: In 72 muscle preparations of SR patients contractile force was 10.9±1.8 mN/mm2 compared to 3.3±0.9 mN/mm2 (n=48, P<0.01) in AF patients. The positive inotropic effect of isoprenaline was diminished but the stimulatory effect on relaxation and the adenylyl cyclase were not altered in AF patients. The force-frequency relation and the post-rest potentiation were enhanced in atrial myocardium of AF patients. The protein levels of CRC, SERCA, Plb, and Cals were not different between the two groups. In contrast, the Na+/Ca2+-exchanger was upregulated by 67% in atria of AF patients. Conclusions: AF-induced atrial contractile dysfunction is not due to β-adrenergic desensitization or dysfunction of the sarcoplasmic reticulum and thus is based on different cellular mechanisms than a ventricular tachycardia-induced cardiomyopathy. Instead, downregulation or altered function of the L-type Ca2+-channel and an increased Ca2+ extrusion via the Na+/Ca2+-exchanger seem to be responsible for the depressed contractility in remodeled atria. © 2002 Elsevier Science B.V. All rights reserved.