Local transmural action potential gradients are absent in the isolated, intact dog heart but present in the corresponding coronary-perfused wedge

Abstract

The left ventricular (LV) coronary‐perfused canine wedge preparation is a model commonly used for studying cardiac repolarization. In wedge studies, transmembrane potentials typically are recorded; whereas, extracellular electrical recordings are commonly used in intact hearts. We compared electrically measured activation recovery interval (ARI) patterns in the intact heart with those recorded at the same location in the LV wedge preparation. We also compared electrically recorded and optically obtained ARIs in the LV wedge preparation. Five Langendorff‐perfused canine hearts were paced from the right atrium. Local activation and repolarization times were measured with eight transmural needle electrodes. Subsequently, left ventricular coronary‐perfused wedge preparations were prepared from these hearts while the electrodes remained in place. Three electrodes remained at identical positions as in the intact heart. Both electrograms and optical action potentials were recorded (pacing cycle length 400–4000 msec) and activation and repolarization patterns were analyzed. ARIs found in the subepicardium were shorter than in the subendocardium in the LV wedge preparation but not in the intact heart. The transmural ARI gradient recorded at the cut surface of the wedge was not different from that recorded internally. ARIs recorded internally and at the cut surface in the LV wedge preparation, both correlated with optically recorded action potentials. ARI and RT gradients in the LV wedge preparation differed from those in the intact canine heart, implying that those observations in human LV wedge preparations also should be extrapolated to the intact human heart with caution.

The roles of mid-myocardial and epicardial cells in T-wave alternans development: a simulation study

“…The limitation of the current study comprises the simplified geometry and simulation scenario of AP propagation, with predefined AP shapes and transmural AP duration heterogeneity as the only baseline APD gradient. The recent studies such as done by Opthof et al and Boukens et al indicated, that in in vivo experiments the transmural gradient is not normally predominant [ 44 , 45 ]. In the work done by Arteyeva et al it was concluded that the T-wave genesis depends on an interaction of several gradients (apex-base, anterior–posterior, RV–LV) [ 46 ].…”

Mechanisms of Arrhythmias in the Brugada Syndrome

“…Thus far, no report fully excluded the possibility of two seemingly opposing mechanisms occurring in the same setting. A critical point of debate however remains the fact that the repolarization hypothesis derives its support, not from the true setting occurring in patients, but mainly experimental models including canine ventricular wedge preparations which were previously found to fail in reproducing the same extent of arrhythmogenesis as in intact canine hearts [ 69 , 90 , 91 ]. One of the few clinical studies in support of the repolarization hypothesis, Morita and colleagues showed that in Brugada syndrome patients, leads corresponding to the RVOT consistently showed a longer QT interval of which dispersion was increased by blocking sodium current ( I Na ) with pilsicainide [ 87 , 92 ].…”

Low-Frequency Oscillations in Cardiac Sympathetic Neuronal Activity

“…However, mapping studies using arterially perfused left ventricular wedge preparations and intact hearts suggest that transmural repolarization differences do not fully explain T wave genesis (Opthof et al, 2007;Boukens et al, 2015). By comparing electrical and optical mapping of both intact and left ventricular wedge preparation of canine hearts, Boukens et al (2017) demonstrated that electrical gradients from wedge preparations differed from those of intact hearts, implying that findings from wedge preparations may not extrapolate to the whole heart.…”