BACKGROUND: In single heart cells, abrupt changes in stimulation rate elicit complex alterations in repolarization. The effects of rate change on dispersion of repolarization, however, have not been well characterized. METHODS AND RESULTS: To determine the effects of abrupt cycle length (CL) shortening on spatial inhomogeneity of repolarization in a syncytium of ventricular cells, 124 action potentials were simultaneously recorded from Langendorff-perfused guinea pig hearts using high-resolution optical mapping with voltage-sensitive dye. The distribution of ventricular action potential durations (APDs) mapped during each cardiac cycle was used to calculate mean APD and repolarization dispersion index (DI), defined as the variance of the distribution. After abruptly shortening CL from 500 to 300 msec, mean APD declined exponentially in normoxic controls (by 23 +/- 3 msec, p less than 0.0001). This response was characterized by beat-to-beat oscillations of APD that were synchronized at all ventricular sites. After 30 minutes of hypoxia, mean APD decreased from 175.0 +/- 13.3 to 76 +/- 25.7 msec. However, during hypoxia, abrupt CL shortening lowered mean APD by only an additional 6 +/- 6 msec, and APD oscillations were no longer synchronized throughout the ventricle. In controls, beat-to-beat DI decreased significantly (-51.0 +/- 6.8%, p less than 0.01) by the sixth post-CL shortening beat and then recovered (by 15-20 beats). In contrast, DI failed to decrease during hypoxia (+7.1 +/- 23%). Two mechanisms for the transient decline of DI in controls were identified: synchronous APD oscillations and transient diminution of the apical-to-basal ventricular APD gradient. CONCLUSIONS: These data demonstrate that inhomogeneity of ventricular repolarization, as measured by DI, changes dynamically with CL shortening. Furthermore, the hypoxic ventricle does not attenuate DI after abrupt CL shortening and thereby lacks a physiological response expected to diminish vulnerability to arrhythmias.
BACKGROUND: In single heart cells, abrupt changes in stimulation rate elicit complex alterations in repolarization. The effects of rate change on dispersion of repolarization, however, have not been well characterized. METHODS AND RESULTS: To determine the effects of abrupt cycle length (CL) shortening on spatial inhomogeneity of repolarization in a syncytium of ventricular cells, 124 action potentials were simultaneously recorded from Langendorff-perfused guinea pig hearts using high-resolution optical mapping with voltage-sensitive dye. The distribution of ventricular action potential durations (APDs) mapped during each cardiac cycle was used to calculate mean APD and repolarization dispersion index (DI), defined as the variance of the distribution. After abruptly shortening CL from 500 to 300 msec, mean APD declined exponentially in normoxic controls (by 23 +/- 3 msec, p less than 0.0001). This response was characterized by beat-to-beat oscillations of APD that were synchronized at all ventricular sites. After 30 minutes of hypoxia, mean APD decreased from 175.0 +/- 13.3 to 76 +/- 25.7 msec. However, during hypoxia, abrupt CL shortening lowered mean APD by only an additional 6 +/- 6 msec, and APD oscillations were no longer synchronized throughout the ventricle. In controls, beat-to-beat DI decreased significantly (-51.0 +/- 6.8%, p less than 0.01) by the sixth post-CL shortening beat and then recovered (by 15-20 beats). In contrast, DI failed to decrease during hypoxia (+7.1 +/- 23%). Two mechanisms for the transient decline of DI in controls were identified: synchronous APD oscillations and transient diminution of the apical-to-basal ventricular APD gradient. CONCLUSIONS: These data demonstrate that inhomogeneity of ventricular repolarization, as measured by DI, changes dynamically with CL shortening. Furthermore, the hypoxic ventricle does not attenuate DI after abrupt CL shortening and thereby lacks a physiological response expected to diminish vulnerability to arrhythmias.
Authors: Rajkumar Mantravadi; Bethann Gabris; Tong Liu; Bum-Rak Choi; William C de Groat; G André Ng; Guy Salama Journal: Circ Res Date: 2007-03-15 Impact factor: 17.367
Authors: Ken Wang; Peter Lee; Gary R Mirams; Padmini Sarathchandra; Thomas K Borg; David J Gavaghan; Peter Kohl; Christian Bollensdorff Journal: Am J Physiol Heart Circ Physiol Date: 2015-01-16 Impact factor: 4.733