Investigation of causal interactions between ventricular action potential duration, blood pressure and respiration

Temporal variability of the ventricular action potential duration (APD) is an important electrophysiological parameter associated with arrhythmogenesis. Respiratoryrelated APD oscillations have recently been observed in humans. This study aims to investigate the underlying driving mechanisms by characterizing the causal interactions between APD, systolic blood pressure (SBP) and respiration in humans in vivo. In 12 subjects with normal ventricles undergoing clinical electrophysiological procedures, recordings were made of the endocardial unipolar electrogram, femoral artery pressure and respiration. The activation recovery interval (ARI) was derived from the electrogram as a conventional surrogate for APD. During the experiment, breathing and heart rate were maintained constant. Data was analyzed by computing the directed coherence between ARI, systolic blood pressure (SBP) and respiration at the respiratory frequency using a linear multivariate autoregressive model that describes both lagged and instantaneous effects. The pathways from respiration to ARI and SBP showed a high directed coherence: 0.68(±0.22) and 0.75(±0.12), respectively. In contrast, the mean directed coherence from SBP to ARI was small: 0.08(±0.08). This suggests that APD oscillations at the respiratory frequency are not simply driven by a mechanical component but they are the result of more complex interactions.