Biomedical subjects

Philip R Ershler

Publications and source records attributed to Philip R Ershler.

3 recordsLinked to original sources

PubMed2005

Effect of fiber orientation on propagation: electrical mapping of genetically altered mouse hearts.

BACKGROUND: Epicardial potentials reveal the strong effects of fiber anisotropy, rotation, imbrication, and coupling on propagation in the intact heart. From the patterns of the surface potentials, we can obtain information about the local fiber orientation, anisotropy, the transmural fiber rotation, and which direction the wave front is traveling through the wall. In this study, lessons learned from epicardial potential mapping of large hearts were applied to studies conducted in genetically altered mouse hearts. METHODS: An inducible model of the overexpression of a gain-of-function alpha5 integrin (cytoplasmic domain truncation) was created in mouse. After 3 days of administration of doxycycline, the animals exhibited an altered electrical phenotype of markedly reduced amplitude of the QRS complex on the surface electrocardiogram. Epicardial potentials were recorded from Langendorff-perfused mouse hearts with alpha5 integrin gain-of-function mutations and from wild-type (WT) control hearts. A cylindrical electrode array consisting of 184 sites with 1-mm uniform interelectrode spacing was placed around the heart, and unipolar electrograms were recorded during atrial and ventricular stimulation at different basic cycle lengths. RESULTS: The total ventricular activation time for the transgenic animals was greater than that of the WT hearts for atrial and ventricular pacing locations. The isopotential maps from the mutated hearts showed a loss of anisotropy, as revealed by the more rounded and less elliptically shaped wave fronts seen immediately after epicardial point stimulation when compared with WT hearts. The weaker potential maxima in the mutated hearts did not exhibit the normal expansion and rotation associated with an advancing wave front in a normal heart, suggesting abnormalities in myocyte coupling in these hearts. Isopotential maps provided additional information about fiber architecture from the electric field that was not obtained from optical recordings alone. These findings provided a phenotypic characterization and specific insights into the mechanisms of the electrical abnormalities associated with altered integrin signaling in cardiac myocytes.

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PubMed2003

Cycle length sequence dependent repolarization dynamics.

Cardiac repolarization, particularly its heterogeneity, is known to play a significant role in arrhythmogenesis. Steepness of cardiac restitution, or the cycle length dependency of repolarization, has also been implicated as a condition that favors occurrence of reentrant arrhythmias. However, most assessments of heterogeneity and restitution are based on static observations and do not directly account for the extent or heterogeneity of dynamic changes. The uncertainty and unpredictability of arrhythmias and the difficulty of identifying patients most at risk may possibly be explained by the lack of consideration of dynamic changes of repolarization, its heterogeneity and time varying restitution. In this brief article, we show the global changes in repolarization that occur in normal canine hearts in response to programmed cycle length sequences. Specifically, we show the beat-to-beat tracking of repolarization during rapid (step) changes in cycle length as well as linear up and down (sawtooth) changes, and random cycle length sequences. The measurement and robust characterization of the dynamic repolarization response to specific cycle length sequences may offer an opportunity to characterize the substrate for arrhythmias to a greater extent than has been possible to date. Although there is no guarantee that characterization of repolarization dynamics will provide definitive means to identify patients at risk, such assessment will, at a minimum, put into perspective the role that repolarization dynamics may play in detecting states of increased arrhythmia risk. Another potential use of these techniques is in the assessment of repolarization in patients undergoing EP testing, pharmacological therapies or during other provocative testing.

Animals↗

PubMedDate not supplied

Spatial methods of epicardial activation time determination in normal hearts.

The purpose of this study was to demonstrate errors in activation time maps created using the time derivative method on fractionated unipolar electrograms, to characterize the epicardial distribution of those fractionated electrograms, and to investigate spatial methods of activation time determination. Electrograms (EGs) were recorded using uniform grids of electrodes (1 or 2 mm spacing) on the epicardial surface of six normal canine hearts. Activation times were estimated using the time of the minimum time derivative, maximum spatial gradient, and zero Laplacian and compared with the time of arrival of the activation wave front as assessed from a time series of potential maps as the standard. When comparing activation times from the time derivative for the case of epicardial pacing, spatial gradient and Laplacian methods with the standard for EGs without fractionation, correlations were high (R2 = 0.98, 0.98, 0.97, respectively). Similar comparisons using results from only fractionated EGs (R2 = 0.85,0.97,0.95) showed a lower correlation between times from the time derivative method and the standard. The results suggest an advantage of spatial methods over the time derivative method only for the case of epicardial pacing where large numbers of fractionated electrograms are found.

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