Repolarization Of Epicardium Research Articles

Electrocardiographic marker of the cardiac action potential triangulation induced by antiarrhythmic drugs in perfused guinea-pig heart.

What is the central question of this study? Can the triangular appearance of ventricular action potential, indicating proarrhythmic profile of antiarrhythmic agent, be approximated by specific changes on an electrocardiogram (ECG)? What are the main finding and its importance? The triangulation of the ventricular action potential seen when antiarrhythmic drugs induce a greater lengthening of the late repolarization compared to the initial repolarization in epicardium is closely approximated by a greater prolongation of the T wave upslope relative to the interval between the J point and the start of the T wave (the JTstart interval) on the ECG. These findings may improve the power of ECG assessments in predicting the drug-induced arrhythmia resulting from slowed phase 3 repolarization. Antiarrhythmic drugs prescribed to treat atrial fibrillation can occasionally precipitate ventricular tachyarrhythmia through a prominent slowing of the phase 3 repolarization. The latter results in the triangular shape of ventricular action potential, indicating high arrhythmic risk. However, clinically, the utility of triangulation assessments for predicting arrhythmia is limited owing to the invasive nature of the ventricular action potential recordings. This study examined whether the triangulation effect can be detected indirectly from electrocardiogram (ECG) analysis. Epicardial monophasic action potentials and the ECG were simultaneously recorded in perfused guinea-pig hearts. With antiarrhythmics (dofetilide, quinidine, procainamide and flecainide), a prolongation of the initial repolarization seen in the action potential recordings was closely approximated by lengthening of the interval between the J point and the start of the T wave (the JTstart interval) on the ECG, whereas a prolongation of the late repolarization was paralleled by widening of the T wave upslope. Dofetilide, quinidine and procainamide induced a prominent slowing of the phase 3 repolarization in epicardium, leading to triangulation of the action potential. These effects were accompanied by a greater prolongation of the T wave upslope compared to the JTstart interval. Flecainide elicited a proportional prolongation of the initial and the late ventricular repolarization, and therefore failed to induce triangulation, based on analysis of both epicardial action potential and ECG profiles. Collectively, these findings suggest that the ratio between the durations of the T wave upslope and the JTstart interval may represent the ECG metric of the ventricular action potential triangulation induced by antiarrhythmic drugs.

Impact of SR Ca2+ Release on the Cardiac Action Potential Repolarization during Postnatal Development

In heart, the excitation-contraction coupling (ECC) mechanism changes from sarcolemmal Ca2+ diffusion in newborn, to Ca2+ induced Ca2+ release in adult. This implies different contribution of the sarcoplasmic reticulum (SR). Since SR Ca2+ release (SRCa) deeply influences sarcolemmal Ca2+ fluxes, we hypothesized that the differential contribution of the SRCa to ECC during postnatal development is critical in defining the properties of AP repolarization in epicardium. Consequently, the AP properties were evaluated during postnatal development in correlation with the SRCa contribution to ECC. To this end, the temperature dependence of the epicardical AP properties was determined with the local-field fluorescence detection method in intact mouse hearts, with/without SRCa, and at various ages after birth (7h, 1d, 2d, 7d, & AD). Our pharmacological (ryanodine+thapsigargin) and thermodynamic (temperature dependence from 21°-37°C) studies confirmed that the SRCa contribution becomes more prominent with development. More importantly, they showed that the impact of SRCa on the AP duration (measured at 25% & 75% of repolarization; APD25 & APD75) exhibits a biphasic effect. At day 2, SRCa significantly reduced the APD25 & APD75 by 38.7% & 31%, respectively; while in adult SRCa prolonged the APD75 by 49.7%; with day 7 being a transitional stage with a 44%-shortened APD25 and 25%-lengthened ADP75. Interestingly, the peak-and-dome AP morphology typical of mouse ventricular myocytes, became evident only in adult. A possible explanation for this dual effect on APD is that early after birth, SRCa promotes a Ca2+-dependent inactivation of the L-type ICa while in adult, SRCa activates the Na-Ca exchanger forward mode. Altogether, our results demonstrated that differences in SR Ca2+ release during development not only play a different role in ECC, but greatly impacts plasma membrane excitability as well. Supported by NIH R01-HL-084487 to AE.

Mechanism of Brugada type ECG: Late repolarization in epicardium at right ventricular outflow tract

Mechanism of Brugada type ECG: Late repolarization in epicardium at right ventricular outflow tract

Cellular and ionic basis for T-wave alternans under long-QT conditions.

T-wave alternans (TWA), an ECG phenomenon characterized by beat-to-beat alternation of the morphology, amplitude, and/or polarity of the T wave, is commonly observed in the acquired and congenital long-QT syndromes (LQTS). This study examines the cellular and ionic basis for TWA induced by rapid pacing under conditions mimicking the LQT3 form of the congenital LQTS in an arterially perfused canine left ventricular wedge preparation. Transmembrane action potentials from epicardial, M, and endocardial cells and 6 to 8 intramural unipolar electrograms were simultaneously recorded together with a transmural ECG and isometric tension development. In the presence of sea anemone toxin (ATX-II; 20 nmol/L), an increase in pacing rate (from a cycle length [CL] of 500 to 400 to 250 ms) produced a wide spectrum of T-wave and mechanical alternans. Acceleration to CLs of 400 to 300 ms produced mild to moderate TWA principally due to beat-to-beat alternation of repolarization of cells in the M region. Transmural dispersion of repolarization during alternans was exaggerated during alternate beats. Acceleration to CLs of 300 to 250 ms caused more pronounced beat-to-beat alternation of action potential duration (APD) of the M cell, resulting in a reversal of repolarization sequence across the ventricular wall, leading to alternation in the polarity of the T wave. The peak of the negative T waves coincided with repolarization of the M region, whereas the end of the negative T wave coincided with the repolarization of epicardium. In almost all cases, electrical alternans was concordant with mechanical alternans. Torsade de pointes occurred after an abrupt acceleration of CL, which was associated with marked TWA. Both ryanodine and low [Ca2+]o completely suppressed alternans of the T wave, APD, and contraction, suggesting a critical role for intracellular Ca2+ cycling in the maintenance of TWA. Our results suggest that TWA observed at rapid rates under long-QT conditions is largely the result of alternation of the M-cell APD, leading to exaggeration of transmural dispersion of repolarization during alternate beats, and thus the potential for development of torsade de pointes. Our data also suggest that unlike transient forms of TWA that damp out quickly and depend on electrical restitution factors, the steady-state electrical and mechanical alternans demonstrated in this study appears to be largely the result of beat-to-beat alternans of [Ca2+]i.