Epicardial multielectrode array (MEA) mapping of both left and right atrial conduction properties were performed during either sinus rhythm or PES, in isolated Langendorff‐perfused hearts. Figure 3A exemplifies activation maps through five successive cardiac cycles from young (a and b) and old (c and d),  Mkk4F/F (a and c), and Mkk4ACKO hearts (b and d). Most activation maps from Mkk4F/F hearts showed a sequential activation pattern, beginning with a localized activation of one region of the matrix followed by its successive spread to the remaining area from which recordings were made. This suggests an orderly spread of excitation within the plane of the epicardium (a and c). However, the old Mkk4ACKO hearts often showed a more disordered excitation sequence.

It was also possible to determine conduction velocities within the right and left atria by using MEA recordings to follow the pattern of spread from stimuli delivered through a point in the center of, rather than adjoining, the array and color coding the delays in arrival times as the resulting AP spreads from the site of stimulation. The resulting velocities were comparable in young (3‐month) Mkk4F/F and Mkk4ACKO hearts (Figure 3Ba, b). However, old Mkk4ACKO atria showed slower conduction than old Mkk4F/F hearts. The isochronal maps thus illustrated a pattern consistent with a slower conduction in both left and right Mkk4ACKO than in Mkk4F/F atria from 12‐month‐old hearts (Figure 3Ba, b). Mkk4 deletion thus both alters conduction properties and increases atrial arrhythmic susceptibility, particularly in old Mkk4ACKO mice

Figure 3

Epicardial electrical mapping with a multielectrode array (MEA). A, Representative activation maps of five successive cardiac cycles under sinus rhythm in Mkk4F/F (a and c) and Mkk4ACKO hearts (b and d) grouped by age in 3‐ (a and b) and 12 month‐old hearts (c and d). B, Representative pacing‐induced activation maps generated by pacing in the center of array on the epicardium of the right (RA) and left atria (LA) of Mkk4F/F and Mkk4ACKO mice (a). Velocities in the left (LA) and right atrium (RA) of young and old Mkk4F/F and Mkk4ACKO mice are shown as bar graphs (means±SEM). Following Shapiro‐Wilk tests for normality, data were compared between groups using the paired Student t test, with a value of P<0.05 considered to indicate statistical significance (b). (n=5 per group). Mkk4ACKO indicates atrial cardiomyocyte specific mitogen‐activated protein kinase kinase 4 knockout mice; Mkk4F/F, Mkk4 flox/flox.

Journal of the American Heart Association Volume 3, Number 2

https://doi.org/10.1161/JAHA.113.000340