HYPOXIA AND HYPOTHERMIA ENHANCE SPATIAL HETEROGENEITIES OF REPOLARIZATION IN GUINEA-PIG HEARTS - ANALYSIS OF SPATIAL AUTOCORRELATION OF OPTICALLY RECORDED ACTION-POTENTIAL DURATIONS

Spatial Autocorrelation of APDs During Arrhythmogenic Insults, Introdu ction: 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 analyz ed because previous algorithms did not take into account spatial heter ogeneities of action potential durations (APDs). Earlier simulations p roposed that pathologic conditions enhance DOR by decreasing electrica l coupling between cells, thereby unmasking differences in cellular re polarization 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 quantit atively characterize APD gradients and DOR to determine how they are i nfluenced by tissue anisotropy and cell coupling during diverse arrhyt hmogenic insults such as hypoxia and hypothermia. Methods and Results: Voltage-sensitive dyes were used to map APs from 124 sites on the epi cardium of Langendorff-perfused guinea pig hearts during (1) cycles of hypoxia and reoxygenation and (2) after 30 minutes of hypothermia (32 degrees to 25 degrees C). We introduce an approach to quantitate DOR by analyzing two-dimensional spatial autocorrelation of APDs along dir ections perpendicular and parallel to the longitudinal axis of epicard ial fibers. A spatial correlation length L was derived as a statistica l measure of DOR. It corresponds to the distance over which APDs had c omparable values, where L is inversely related to DOR. Hypoxia (30 min ) caused a negligible decrease in longitudinal theta(L) (from 0.530 +/ - 0.138 to 0.478 +/- 0.052 m/sec) and transverse theta(T) (from 0.225 +/- 0.034 to 0.204 +/- 0.021 m/sec) conduction velocities and did not alter theta(L)/theta(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 i ndicated by reductions of L from 1.8 +/- 0.9 to 1.1 +/- 0.5 mm (P < 0. 005). Hypothermia caused marked reductions of theta(L) (0.53 +/- 0.138 to 0.298 +/- 0.104 m/sec) and theta(T) (0.225 +/- 0.034 to 0.138 +/- 0.027 m/sec), increased APDs (128 +/- 4.4 to 148 +/- 14.5 msec), and r educed L from 2.0 +/- 0.3 to 1.3 +/- 0.6 mm (P < 0.05). L decreased wi th increased time of hypoxia and recovered upon reoxygenation. Hypoxia and hypothermia reduced L measured along the longitudinal (L-L) and t ransverse (L-T) axes of cardiac fibers while the ratio of L-L/L-T rema ined constant.