Key result
Mitral valve disease or low LVEF linked to downregulated right atrial L-type calcium current.
Why the study?
A decrease in L-type calcium current (ICaL) favors atrial fibrillation, but the pathogenic factors associated with ICaL downregulation remained to be identified.
Observational (n=86)
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“Dinanian et al. report on calcium current measurements made from right atrial myocytes isolated from an impressively large series of 86 cardiac surgery patients, with varying indications for cardiac surgery. Here the authors report that mitral valve disease and atrial dilatation independent of AF are accompanied by reductions in ICa,L that are as substantial as those changes associated with AF. Further, they report that a low ejection fraction has a similar effect on those patients presenting for surgery in sinus rhythm.”
Downregulation of L-type calcium current is present in atrial myocytes of patients in sinus rhythm at high risk for AF, particularly those with mitral valve disease or reduced LVEF.
AIMS: A decrease in L-type calcium current (ICaL) is an important mechanism favouring atrial fibrillation (AF). Here, we aimed to identify pathogenic factors associated with ICaL downregulation. METHODS AND RESULTS: Atrial myocytes were isolated from right atrial appendages obtained from 86 adult patients in sinus rhythm with coronary artery disease, aortic valve disease, or mitral valve disease (MVD). Current was recorded in isolated myocytes using the whole-cell patch-clamp technique. The ICaL recorded in the 172 myocytes studied showed a marked variability of peak density ranging from 0.1 to 9.0 pA/pF. The ICaL peak density did not correlate with membrane capacitance or changes in current biophysical properties. The ICaL peak density was homogeneous for a given sample. Small ICaL values were recorded in patients with MVD or with a low left ventricular ejection fraction (<45%). Small ICaL values were more sensitive to the beta-adrenergic agonist, isoproterenol (1 microM), and to the phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine (10 microM). CONCLUSION: In human atrial myocytes, the variability of ICaL is related to the clinical history of the donors. The downregulation of ICaL is already observed in patients in sinus rhythm with a high risk of AF and is associated with the greatest response to beta-adrenergic agonist.
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Dinanian et al. (2008) conducted an observational in Sinus rhythm with coronary artery disease, aortic valve disease, or mitral valve disease (n=86). Mitral valve disease or low left ventricular ejection fraction (<45%) was evaluated on L-type calcium current (ICaL) peak density. In patients in sinus rhythm, mitral valve disease or low left ventricular ejection fraction (<45%) was associated with downregulated L-type calcium current in right atrial myocytes.
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