Page 17 - ADD-ON ABLATION SURGERY IN PATIENTS WITH ATRIAL FIBRILLATION

Modulating Factors
Currently, there is an intense research interest in the role of inflammation in the 1 pathophysiology of AF 70, 71. Inflammatory indexes, mainly C-reactive protein (CRP)
have been related to future AF development, AF recurrences after cardioversion,
and to the persistence of the arrhythmia72. The role of inflammation in the
pathogenesis of LAF remains equivocal and limited. Indeed, only the study by Frustaci et al73 demonstrated abnormal atrial histology in most of the patients with paroxysmal LAF refractory to conventional anti-arrhythmic therapy (inflammatory infiltrates in 66% of patients).
Conversely, other investigators failed to show inflammatory changes in LA histological specimens from LAF patients74. Furthermore, Ellinor et al.75 failed to demonstrate increased CRP levels in patients with LAF compared to controls while the opposite was observed in patients with AF and hypertension. It has therefore been postulated that markers of inflammation are associated with the presence of other concomitant diseases73. Another case-control study showed elevated CRP levels in LAF patients; however, subjects with hypertension had not been excluded76. An imbalance of autonomic nerve activity has been implicated in the initiation of AF77. Parasympathetic nerves (which slow heart rate) and sympathetic nerves (which increase heart rate) can both initiate AF, due to shortening of the atrial effective refractory period and to changes in intracellular calcium cycling78, 79.The pulmonary veins are a primary location for entry of vagal nerves into the left atrium80, 81. Depending on the branches, stimulated vagal activity can cause slowing of heart rate, slowing of atrio-ventricular nodal conduction, or heterogeneous shortening of atrial action potentials; these effects result from activation of the potassium channels coupled to muscarinic (M2) receptors that are present at high density in atrial and nodal myocytes82.
Results from experimental studies on isolated canine pulmonary vein preparations suggest that simultaneous sympathetic and parasympathetic (adrenergic and cholinergic) stimulation is most effective at promoting PV ectopy,by simultaneously stimulating calcium overload while abbreviating the effective refractory period83. In addition,Armour and colleagues84 were the first to document the presence of an intrinsic cardiac nervous system, consisting of bundles of neurons (ganglionic plexuses, GP) located in multiple atrial and ventricular locations83. They noted that activity of these GP neurons could modify cardiac activity. Ganglionic plexuses are embedded in fat pads on the epicardium of the heart. Stimulation of GP located at the PV–atrial junction has been reported to convert PV focal
Introduction
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