Abstract-The analysis of surface-activation patterns and measurements of conduction velocity in ventricular myocardium is complicated by the fact that the electrical wavefront has a complex 3D shape and can approach the heart surface at various angles. Recent theoretical studies suggest that the optical upstroke is sensitive to the subsurface orientation of the wavefront. Our goal here was to (1) establish the quantitative relationship between optical upstroke morphology and subsurface wavefront orientation using computer modeling and (2) test theoretical predictions experimentally in isolated coronary-perfused swine right ventricular preparations. We show in numerical simulations that by suitable placement of linear epicardial stimulating electrodes, the angle of wavefronts with respect to the heart surface can be controlled. Using this method, we developed theoretical predictions of the optical upstroke shape dependence on . We determined that the level V F * at which the rate of rise of the optical upstroke reaches the maximum linearly depends on . A similar relationship was found in simulations with epicardial point stimulation. The optical mapping data were in good agreement with theory. Plane waves propagating parallel to myocardial fibers produced upstrokes with V F *Ͻ0.5, consistent with theoretical predictions for Ͼ0. Similarly, we obtained good agreement with theory for plane waves propagating in a direction perpendicular to fibers (V F *Ͼ0.5 when Ͻ0). Finally, during epicardial point stimulation, we discovered characteristic saddle-shaped V F * maps that were in excellent agreement with theoretically predicted changes in during wavefront expansion. Our findings should allow for improved interpretation of the results of optical mapping of intact heart preparations. Key Words: optical action potential Ⅲ conduction velocity Ⅲ optical mapping Ⅲ voltage-sensitive dye P atterns of electrical activation within the ventricular wall are determined in large part by the specific 3D organization of myocardial fibers. Histological studies of intact hearts from many species have shown conclusively that myocardial fiber orientation rotates significantly across the heart wall. 1 The total angle of rotation across the myocardial wall can reach 180°. 2 Because of the complex transmural organization of myocardial fibers, an excitation wavefront typically assumes a complex 3D profile that, depending on the mode of stimulation, can approach the myocardial surface at a variety of different angles. [3][4][5][6] For this reason, obtaining accurate quantitative information about the wavefront orientation with respect to the surface is quite important for the interpretation of surface recordings, particularly with regard to measurements of conduction velocity.In a recent modeling study, 7 we discovered that the upstroke morphology of optical action potentials (OAPs) was sensitive to the local subsurface orientation of the excitation wavefront. This suggests that analysis of OAP upstroke morphology may prove useful in determini...

While ventricular gap junctions contain only Cx43, atrial gap junctions contain both Cx40 and Cx43; yet the functional consequences of this co-expression remain poorly understood. We quantitated the expression of Cx40 and Cx43 and their contributions to atrial gap junctional conductance (g j ). Neonatal murine atrial myocytes showed similar abundances of Cx40 and Cx43 proteins, while ventricular myocytes contained at least 20 times more Cx43 than Cx40. Since Cx40 gap junction channels are blocked by 2 mM spermine while Cx43 channels are unaffected, we used spermine block as a functional dual whole cell patch clamp assay to determine Cx40 contributions to cardiac g j . Slightly more than half of atrial g j and ≤20% of ventricular g j were inhibited. In myocytes from Cx40 null mice, the inhibition of ventricular g j was completely abolished, and the block of atrial g j was reduced to < 20%. Compared to ventricular gap junctions, the transjunctional voltage (V j )-dependent inactivation of atrial g j was reduced and kinetically slowed, while the V j -dependence of fast and slow inactivation was unchanged. We conclude that Cx40 and Cx43 are equally abundant in atrium and make similar contributions to atrial g j . Co-expression of Cx40 accounts for most, but not all, of the differences in the V j -dependent gating properties between atrium and ventricle that may play a role in the genesis of slow myocardial conduction and arrhythmias.

Computer modelling predicts that ischaemia-related arrhythmias are triggered by calcium-mediated alternating conduction blocks in the ischaemic border zone. Alternating conduction blocks lead to intramural reentry and APD alternans.

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