Atrial fibrillation and autonomic nervous system: A translational approach to guide therapeutic goals

Figures

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  FIGURE 1. Effects of parasympathetic and sympathetic activation on cardiomyocyte. Vagal activation (indicated in orange) of muscarinic acetylcholine receptors (MAChRs) secondary to the release of the acetylcholine (ACh), influences G‐protein regulated inward‐rectifier K+ (GIRK) and determines GTP‐binding to subunit Gα (releasing Gβγ) and consequent activation of the ACh‐gated potassium currents (Ik,ACh). Sympathetic cascade (showed in orange) starts with β receptor activation followed by GPT‐binding to Gα, dissociation from subunits Gβ and Gγ, conversion‐adenylate cyclase (AC) dependent of ATP to cAMP, Ca2+ phosphorylation and finally activation of L‐Type Ca2+ channel at level of cytoplasmic membrane causing inward Ca2+ currents. In the same time activation of ryanodine receptor (RyR2) promotes outward Ca2 + currents from sarcoplasmic reticulum (SR) to cytoplasm. Finally, phoshorilamban phosphorylation promote SR Ca2+ uptake‐ATP mediated

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  FIGURE 2. Autonomic Nervous System related‐mechanisms of AF beginning and maintenance The focal (white asterisk) mechanism of AF is mostly due to sympathetic contribution (orange lines and arrows) in order to promote trigger activity via automaticity (due to decreased inward‐rectifier K+ current and increased funny current during diastolic depolarization), genesis of EADs that influence phase 2 of the AP and DADs (due to the calcium overload and abnormal calcium release by the sarcoplasmic reticulum). Another mechanism of focal AF is related to induction of EADs during late phase 3 (red lines and arrows) due to the interaction between parasympathetic system through GIRK channels activation and sympathetic system through the increasing of intracellular calcium transient. Parasympathetic nervous system plays an important role for re‐entrant mechanism (violet lines and arrows). Finally, dynamic factors (yellow) can play an important role in this complex mechanism. (EADs, early after depolarizations; DADs, delayed after depolarization; AP, action potential; GIRK, G‐protein regulated inward‐rectifier K+.)

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  FIGURE 3. Simplified representation of the anatomical right and left atrial GP ablation in relation to topographic location of ganglion gateways (A) and of the most important GPs in anatomical studies (B). (IRGP, inferior right ganglionated plexi; ARGP, anterior right ganglionated plexi; ILGP, inferior left ganglionated plexi; SLGP, superior left ganglionated plexi; SVC, superior vena cava; IVC, inferior vena cava; CSo, coronary sinus ostium; RA, right atrium; LA, left atrium. (B) Image from Armour JA, Murphy DA, Yuan BX, et al Gross and microscopic anatomy of the human intrinsic cardiac nervous system. Anat Rec 1997; 1997 Feb;247(2):289‐98)

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  FIGURE 4. Perspectives future regarding electroanatomic voltage map (CARTO 3) of the left atrial signals with characterization of low amplitude fragmented signals (LAFE; A) and high amplitude fragmented signals (HAFE; B)

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  FIGURE 5. Representation of current and future perspectives regarding direct and non‐direct‐cardiac neuromodulation. (AAD, new antiarrhythmic drugs; VNS, vagal nerve stimulation; SG, stellate ganglion; OSA, obstructive sleep apnea; GERD, gastroesophageal reflux disease)