Cellular mechanisms of depressed atrial contractility in patients with chronic atrial fibrillation

Background-After cardioversion of atrial fibrillation (AF), the contractile function of the atria is temporarily impaired. Although this has significa nt clinical implications, the underlying cellular mechanisms are poorly und erstood. Methods and Results-Forty-nine consecutive patients submitted for mitral va lve surgery were investigated. Twenty-three were in persistent AF (greater than or equal to3 months); the others were in sinus rhythm. Before extracor poral circulation, the right atrial appendage was excised. beta -Adrenocept ors were quantified by radioligand binding, and G proteins were quantified by Western blot analysis. The isometric contractile response to Ca2+, isopr oterenol, Bay K8644, and the postrest potentiation of contractile force wer e investigated in thin atrial trabeculae, which were also examined histolog ically. The contractile force of the atrial preparations obtained from AF p atients was 75% less than that in preparations from patients in sinus rhyth m. Also, the positive inotropic effect of isoproterenol was impaired, and B ay K8644 failed to increase atrial contractile force, In contrast, the resp onse to extracellular Ca2+ was maintained, and the postrest potentiation wa s preserved. P-Adrenoceptor density and G-protein expression were unchanged . Histological examination revealed 14% more myolysis in the atria of AF pa tients. Conclusions-After prolonged AF, atrial contractility was reduced by 75%, Th e impairment of P-adrenergic modulation of contractile force cannot be expl ained by downregulation of beta -adrenoceptors or changes in G proteins. Dy sfunction 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 ap paratus itself is nearly completely preserved after prolonged AF.