Characteristics of electromechanical window in anesthetized rabbit models of short QT and long QT syndromes

Limprasutr, Vudhiporn; Saengklub, Nakkawee; Meedech, Pradtana; Kijtawornrat, Anusak; Hamlin, Robert L.

doi:10.2131/jts.42.579

Cited by 4 publications

(4 citation statements)

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“…New QTc formula for cynomolgus monkeys the amplitudes and durations of the various components of the eCg are useful for detecting cardiac diseases, such as cardiomyopathy. in humans, measurement of the Qt interval of the eCg is considered especially important in the diagnosis of many cardiac diseases [22]. researchers commonly use Qtc rather than Qt in their studies, because the QT interval is affected by heart rate. )…”

Section: Discussionmentioning

confidence: 99%

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Establishment of a new formula for QT interval correction using a large colony of cynomolgus monkeys

et al. 2020

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The demand for monkeys for medical research is increasing, because their ionic mechanism of repolarization is similar to that of humans. The QT interval is the distance between the Q wave and T wave, but this interval is affected by heart rate. Therefore, QT correction methods are commonly used in clinical settings. However, an accurate correction formula for the QT interval in cynomolgus monkeys has not been reported. We assessed snapshot electrocardiograms (ECGs) of 353 ketamine-immobilized monkeys, including aged animals, and contrived a new formula for the corrected QT interval (QTc) as a marker of QT interval prolongation in cynomolgus monkeys. Values for QTc were calculated using the formula [QTc] = [QT] / [RR] n , along with several other formulas commonly used to calculate QTc. We found that the optimal exponent of the QT interval corrected for heart rate, n, was 0.576. The mean value of QTc in healthy monkeys determined using the new formula was 373 ± 31 mm, and there were no significant differences between the sexes. Other ECG parameters were not significantly different between the sexes and there were no age-related effects on QTc. Prolongation of QTc to over 405 ms, as calculated by the new formula, was observed in 50 monkeys with underlying diseases. Additionally, all monkeys with QTc above 440 ms by the new formula had some underlying disease. The results resemble those in humans, suggesting that the new QTc formula could be useful for diagnosis of QT interval prolongation in cynomolgus monkeys.

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Section: Discussionmentioning

confidence: 99%

“…Anim. 2020; 69(1): [18][19][20][21][22][23][24][25] For good maintenance and management of experimental animals, it is necessary to detect any underlying diseases or disorders at an early stage in order to increase the efficiency of research.…”

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confidence: 99%

Establishment of a new formula for QT interval correction using a large colony of cynomolgus monkeys

et al. 2020

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“…In contrast to LQTS, where the EMW is pathologically negative, in SQTS, it is pathologically positive (in the range of +111 ms 114 —in contrast to +22 ms in healthy subjects) ( Figure 4C ). 29 This holds also for other species, such as kangaroos with a notoriously short QT time, 115 and for drug-induced 116 and transgenic SQTS rabbit models, 113 as well as in in silico modelling studies. 110 …”

Section: Electromechanical Reciprocity In Short-qt Syndromementioning

confidence: 94%

Electromechanical reciprocity and arrhythmogenesis in long-QT syndrome and beyond

Odening

Linde

Ackerman

et al. 2022

European Heart Journal

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An abundance of literature describes physiological and pathological determinants of cardiac performance, building on the principles of excitation–contraction coupling. However, the mutual influencing of excitation–contraction and mechano-electrical feedback in the beating heart, here designated ‘electromechanical reciprocity’, remains poorly recognized clinically, despite the awareness that external and cardiac-internal mechanical stimuli can trigger electrical responses and arrhythmia. This review focuses on electromechanical reciprocity in the long-QT syndrome (LQTS), historically considered a purely electrical disease, but now appreciated as paradigmatic for the understanding of mechano-electrical contributions to arrhythmogenesis in this and other cardiac conditions. Electromechanical dispersion in LQTS is characterized by heterogeneously prolonged ventricular repolarization, besides altered contraction duration and relaxation. Mechanical alterations may deviate from what would be expected from global and regional repolarization abnormalities. Pathological repolarization prolongation outlasts mechanical systole in patients with LQTS, yielding a negative electromechanical window (EMW), which is most pronounced in symptomatic patients. The electromechanical window is a superior and independent arrhythmia-risk predictor compared with the heart rate-corrected QT. A negative EMW implies that the ventricle is deformed—by volume loading during the rapid filling phase—when repolarization is still ongoing. This creates a ‘sensitized’ electromechanical substrate, in which inadvertent electrical or mechanical stimuli such as local after-depolarizations, after-contractions, or dyssynchrony can trigger abnormal impulses. Increased sympathetic-nerve activity and pause-dependent potentiation further exaggerate electromechanical heterogeneities, promoting arrhythmogenesis. Unraveling electromechanical reciprocity advances the understanding of arrhythmia formation in various conditions. Real-time image integration of cardiac electrophysiology and mechanics offers new opportunities to address challenges in arrhythmia management.

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“…In male patients with idiopathic ventricular fibrillation (VF), the QT interval was found to be short [ 38 ]. In anesthetized rabbit infused with QT shortening drugs, it was shown that pinacidil shortened the QT interval and induced VF [ 22 ]. However, literatures have demonstrated that the QT interval alone is not sufficient to predict the occurrence of VF in the acute phase of myocardial infarction in rhesus monkeys and human [ 31 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

An increasing electromechanical window is a predictive marker of ventricular fibrillation in anesthetized rabbit with ischemic heart

et al. 2018

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The QTc interval is widely used in Safety Pharmacological studies to predict arrhythmia risk, and the electromechanical window (EMW) and short-term variability of QT intervals (STVQT) have been studied as new biomarkers for drug-induced Torsades de Pointes (TdP). However, the use of EMW and STVQT to predict ventricular fibrillation (VF) has not been elucidated. This study aimed to evaluate EMW and STVQT to predict VF in anesthetized rabbit model of VF. VF was induced by ligation of the left anterior descending and a descending branch of the left circumflex coronary arteries in a sample population of rabbits (n=18). VF was developed 55.6% (10/18). In rabbit with VF, the EMW was significantly higher than in rabbits without VF (96.3 ± 15.6 ms and 49.5 ± 5.6 ms, respectively, P<0.05). STVQT had significantly increased before the onset of VF in rabbits that experienced VF, but not in rabbits that did not experience VF (11.7 ± 1.8 ms and 3.7 ± 0.4 ms, respectively, P<0.05). The EMW and STVQT had better predictive power for VF with higher sensitivity and specificity than the QTc measure. The result suggested that the increasing of EMW, as well as the elevation of STVQT, can potentially be used as biomarkers for predicting of VF.

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Characteristics of electromechanical window in anesthetized rabbit models of short QT and long QT syndromes

Cited by 4 publications

References 30 publications

Establishment of a new formula for QT interval correction using a large colony of cynomolgus monkeys

Establishment of a new formula for QT interval correction using a large colony of cynomolgus monkeys

Electromechanical reciprocity and arrhythmogenesis in long-QT syndrome and beyond

An increasing electromechanical window is a predictive marker of ventricular fibrillation in anesthetized rabbit with ischemic heart

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