of the TGR302Qmodel, atrial electrical stimulation induced ortho-
dromic AV reentrant tachycardia, consistent with anterograde AV
nodal conduction and retrograde conduction via the accessory
pathway [33].
Detailed histological evaluation of serial sections from TGN488I
mice with ventricular pre-excitation has identified its anatomic basis
in this model: myocardial connections are observed to disrupt the
annulus fibrosus (which acts in health to electrically insulate the
ventricles from the atria outside the specialized conducting tissue
axis) and are apparent by 2.5 weeks of age and largely located in the
anteroseptal region close to the His-Purkinje system [32, 37,
38].Theseconnectionsappear torepresentventricularmuscleformed
of vacuolated, glycogen-engorged cardiomyocytes (Fig.4)[ 32].Fig. 4Anatomical substrate for ventricular pre-excitation—disruption of annulus fibrosus integrity in a murine
transgenic model ofPRKAG2cardiomyopathy. Masson’s trichrome stained sections through AV junction
myocardium in TGWT(upper panels,a,b) and TGN488I(lower panels,c,d) mice in the region of the right
paraseptal area demonstrating an intact annulus fibrosus (blue staining, arrowheads) in TGWThearts but an
interrupted annulus with direct contact between atrial and vacuolated ventricular cardiomyocytes (d, asterisk)
in TGN488Imice; scale bar 200μm (Reproduced from ref.32 with permission from Wolters Kluwer Health, Inc.)
592 Arash Yavari et al.