Background-Progressive activation delay starting at long coupling intervals of premature stimuli has been shown to correlate with sudden cardiac death in patients with hypertrophic cardiomyopathy. The purpose of this study was to elucidate the mechanism of increased activation delay in chronically diseased myocardium. Methods and Results-High-resolution unipolar mapping (105, 208, or 247 recording sites with interelectrode distances of 0.8, 0.5, or 0.3 mm, respectively) of epicardial electrical activity was carried out during premature stimulation in 11 explanted human hearts. The hearts came from patients who underwent heart transplantation and were in the end stage of heart failure (coronary artery disease, 4; hypertrophic cardiomyopathy, 1; and dilated cardiomyopathy, 6). Eight hearts were Langendorff-perfused. Epicardial sheets were taken from the remaining hearts and studied in a tissue bath. Activation maps and conduction curves were constructed and correlated with histology. Conduction curves revealing prominent increase of activation delay were associated with zones of dense, patchy fibrosis with long fibrotic strands. Dense, diffuse fibrosis with short fibrotic strands only marginally affected conduction curves. The course of conduction curves in patchy fibrotic areas greatly depended on the direction of propagation relative to fiber direction. Conclusions-The study demonstrates that in chronically diseased human myocardium, nonuniform anisotropic characteristics imposed by long fibrotic strands cause a progressive increase of activation delay, starting at long coupling intervals of premature stimuli. The increase strongly depends on the direction of the wave front with respect to fiber direction and the architecture of fibrosis.

Background-Paroxysmal atrial fibrillation in patients is often initiated by foci in the pulmonary veins. The mechanism of these initiating arrhythmias is unknown. The aim of this study was to determine electrophysiological characteristics of canine pulmonary veins that may predispose to initiating arrhythmias. Methods and Results-Extracellular recordings were obtained from the luminal side of 9 pulmonary veins in 6Langendorff-perfused dog hearts after the veins were incised from the severed end to the ostium. Pulmonary veins were paced at the distal end, the ostium, and an intermediate site. During basic and premature stimulation, extracellular electrical activity was recorded with a grid electrode that harbored 247 electrode terminals. In 4 hearts, intracellular electrograms were recorded with microelectrodes. Myocyte arrangement immediately beneath the venous walls was determined by histological analysis in 3 hearts. Extracellular mapping revealed slow and complex conduction in all pulmonary veins. Activation delay after premature stimulation could be as long as 96 ms over a distance of 3 mm. Action potential duration was shorter at the distal end of the veins than at the orifice. No evidence for automaticity or triggered activity was found. Histological investigation revealed complex arrangements of myocardial fibers that often showed abrupt changes in fiber direction and short fibers arranged in mixed direction. Conclusions-Zones of activation delay were observed in canine pulmonary veins and correlated with abrupt changes in fascicle orientation. This architecture of muscular sleeves in the pulmonary veins may facilitate reentry and arrhythmias associated with ectopic activity.

It is known that autonomic nervous activities change in correspondence with sleep stages. However, the characteristics of continuous fluctuations in nocturnal autonomic nerve tone have not been clarified in detail. The study aimed to determine the possible correlation between the electroencephalogram (EEG) and autonomic nervous activities, and to clarify in detail the nocturnal fluctuations in autonomic nerve activities. Overnight EEGs and electrocardiograms of seven healthy males were obtained. These EEGs were analyzed by fast Fourier transformation algorithm to extract delta, sigma and beta power. Heart rate and heart rate variability (HRV) were calculated in consecutive 5-min epochs. The HRV indices of low frequency (LF), high frequency (HF) and LF/HF ratio were calculated from the spectral analysis of R-R intervals. The sleep stages were manually scored according to Rechtschaffen and Kales' criteria. Low frequency and LF/HF were significantly lower during non-rapid eye movement (NREM) than REM, and were lower in stages 3 and 4 than in stages 1 and 2. Furthermore, delta EEG showed inverse correlations with LF ( r = -0.44, P < 0.001) and LF/HF ( r = -0.41, P < 0.001). In contrast, HF differed neither between REM and NREM nor among NREM sleep stages. Detailed analysis revealed that correlation was evident from the first to third NREM, but not in the fourth and fifth NREM. Delta EEG power showed negative correlations with LF and LF/HF, suggesting that sympathetic nervous activities continuously fluctuate in accordance with sleep deepening and lightening.