Optical Mapping Reveals That Repolarization Spreads Anisotropically and Is Guided by Fiber Orientation in Guinea Pig Hearts

Abstract

Abstract Guinea pig hearts were stained with a voltage-sensitive dye and imaged on a photodiode array to record fluorescent action potentials (APs) from 124 sites. Activation and repolarization patterns were recorded from the epicardium during stimulation at different loci and correlated with the underlying fiber architecture. Endocardial APs were recorded by inserting a light guide into the ventricular cavity or by dissecting out the ventricular free wall to expose the endocardium. In hearts paced on the right atrium to simulate sinus rhythm, activation emerged synchronously over a large area of the ventricular epicardium and spread laterally in 5 to 7 ms. The apparent longitudinal and transverse velocities were 2.66±0.11 and 1.65±0.09 m/s (n=12). In contrast, repolarization began near the apex on the endocardium and spread transmurally in 6±1.3 ms (n=12) and then anisotropically along the epicardium in 25 to 30 ms with apparent maximum (0.53±0.11 m/s) and minimum (0.31±0.10 m/s) repolarization velocities that aligned with the longitudinal and transverse axes of epicardial fibers. When paced on the epicardium, activation of intact hearts (n=12) and perfused sheets (n=8) was anisotropic, with longitudinal (0.85±0.05 m/s) and transverse (0.44±0.04 m/s) conduction velocities that aligned with the epicardial fiber orientation. When activation was initiated at different sites on the epicardium, repolarization always began near the apex and exhibited patterns similar to those obtained under right atrial pacing, but with slower longitudinal (0.41±0.09 m/s) and transverse (0.23±0.07 m/s) repolarization velocities (n=18). In sheets stretched parallel to the longitudinal axis of surface fibers, AP durations (APDs) increased as a function of fiber length, from the length at zero developed tension to 120% of the length at maximum developed tension (L max ). Spatial distributions of APDs did not change during stretches along the rising phase of the length-tension curve. In sheets stretched to 50% of L max , APDs were shorter and more homogeneous on the endocardium (mean APD, 188 ms; ΔAPD, 195−186=9 ms) than on the epicardium (mean APD, 204 ms; ΔAPD, 212−186=26 ms; n=8). In guinea pig hearts, activation is rapid; therefore, repolarization depends primarily on intrinsic spatial heterogeneities of APDs. Consequently, repolarization begins at endocardial cells with the shortest APDs and spreads transmurally and then anisotropically on the surface according to the epicardial cell orientation.