Hypoxia and Hypothermia Enhance Spatial Heterogeneities of Repolarization in Guinea Pig Hearts:

Spatial Autocorrelation of APDs During Arrhythmogenic Insults. Introduction: Regional dispersions of repolarization (DOR) are arrhythmogenic perturbations that are closely associated with reentry. However, the characteristics of DOR have not been well defined or adequately analyzed because previous algorithms did not take into account spatial heterogeneities of action potential durations (APDs). Earlier simulations proposed that pathologic conditions enhance DOR by decreasing electrical coupling between cells, thereby unmasking differences in cellular repolarization between neighboring cells. Optical mapping indicated that gradients of APD and DOR are associated with fiber structure and are largely independent of activation. We developed an approach to quantitatively characterize APD gradients and DOR to determine how they are influenced by tissue anisotropy and cell coupling during diverse arrhythmogenic insults such as hypoxia and hypothermia. Methods and Results: Voltage-sensitive dyes were used to map APs from 124 sites on the epicardium of Langendorff-perfused guinea pig hearts during (1) cycles of hypoxia and reoxygenation and (2) after 30 minutes of hypothermia (32° to 25°C). We introduce an approach to quantitate DOR by analyzing two-dimensional spatial autocorrelation of APDs along directions perpendicular and parallel to the longitudinal axis of epicardial fibers. A spatial correlation length l was derived as a statistical measure of DOR. It corresponds to the distance over which APDs had comparable values, where l is inversely related to DOR. Hypoxia (30 min) caused a negligible decrease in longitudinal θ_L (from 0.530 ± 0.138 to 0.478 ± 0.052 m/sec) and transverse θ_T (from 0.225 ± 0.034 to 0.204 ± 0.021 m/sec) conduction velocities and did not alter θ_L/θ_T or activation patterns. In paced hearts (cycle length [CL] = 300 msec), hypoxia decreased APDs (123 ± 18.2 to 46 ± 0.6 msec; P < 0.001) within 10 to 15 minutes and enhanced DOR, as indicated by reductions of l from 1.8 ± 0.9 to 1.1 ± 0.5 mm (P < 0.005). Hypothermia caused marked reductions of θ_L, (0.53 ± 0.138 to 0.298 ± 0.104 m/sec) and θ_T (0.225 ± 0.034 to 0.138 ± 0.027 m/sec), increased APDs (128 ± 4.4 to 148 ± 14.5 msec), and reduced l from 2.0 ± 0.3 to 1.3 ± 0.6 mm (P < 0.05). l decreased with increased time of hypoxia and recovered upon reoxygenation. Hypoxia and hypothermia reduced l measured along the longitudinal (l ₁) and transverse (l _T) axes of cardiac fibers while the ratio l _L/l _T remained constant.