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Functional Properties of Muscle
Published in Nassir H. Sabah, Neuromuscular Fundamentals, 2020
The time course of the ventricular cardiac AP is illustrated in Figure 10.20. The duration of the AP is about 250 ms, which allows the development of maximal force during a twitch. The absolute refractory period, also known as the effective refractory period (ERP), is about 200 ms. Because this exceeds the contraction time, it is not possible to tetanize cardiac muscle. The ERP limits the maximum frequency to about 250–300 beats/min.
Cryoballoon ablation beyond pulmonary vein isolation in the setting of persistent atrial fibrillation
Published in Expert Review of Medical Devices, 2022
Vincenzo Miraglia, Antonio Bisignani, Luigi Pannone, Saverio Iacopino, Gian-Battista Chierchia, Carlo de Asmundis
Progression of AF was first studied in animal models [8]; shortening of atrial effective refractory period, leading to an increased AF vulnerability, is a consequence of fibrillatory conduction in the atrium. This electrical remodeling ultimately results in a self-perpetuating persistent arrhythmia, sustained by AF-induced structural changes [9]. In particular, the acquired dispersion of atrial refractoriness and the inversion of the rate-dependent accommodation of the action potential increase the stability of reentrant waves and the numbers of multiple wavelets [10,11]; this is a leading mechanism of persistent AF. When dealing with ultrastructural cellular changes, AF induces loss of myofibrils, redistribution of connexins, dedifferentiation to fetal phenotypes, necrosis, apoptosis, inflammation, and especially fibrosis [11].
Predicting the cardiac toxicity of drugs using a novel multiscale exposure–response simulator
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2018
Francisco Sahli Costabal, Jiang Yao, Ellen Kuhl
Our simulated effects of dofetilide on cardiac excitation in Figures 6–8 agree well with the label of Pfizer (2011) and with the results of clinical studies in patients (Abraham et al. 2015). Our simulations support the common notion that, at low doses, dofetilide is a safe drug and effective drug with low pro-arrhythmic risk (Pfizer 2011). For a dofetilide concentration of 1x in Figure 6, it takes our simulation 640 ms to return to the resting state, compared to 450 ms for the baseline case with no drugs in Figure 5. Similar to a recent clinical study, which reported a QT prolongation of 78 ms (Johannesen et al. 2014), our simulation predicts a substantial but safe prolongation of the effective refractory period. This agrees well with the general notion that dofetilide can have dramatic consequences if not dosed correctly (Briceno and Supple 2017): in a retrospective cohort study of 1404 patients loaded on dofetilide for a five-year period, dofetilide was stopped in 105 patients because of QT prologation. A total of 17 patients developed torsades de pointes; of those, 10 had an episode of cardiac arrest and one resulted in death. In agreement with our simulations, the study found a dose-related increase in torsades de pointes, with a higher incidence when taking the 0.500 mg dose twice per day (Abraham et al. 2015). According to the label, the maximum single dose for dofetilide is 0.500 mg (Vicente et al. 2015).
The role of low-level vagus nerve stimulation in cardiac therapy
Published in Expert Review of Medical Devices, 2019
Yuhong Wang, Sunny S. Po, Benjamin J. Scherlag, Lilei Yu, Hong Jiang
Many studies have shown the antiarrhythmic effect of LL-VNS. In 2009, Li et al [6] first reported paradoxical effects of VNS in that cervical LL-VNS administered 1 V below the threshold that slowed the sinus rate or AV conduction, significantly increased the effective refractory period (ERP), suppressed atrial fibrillation (AF) inducibility and shortened the AF duration at all pulmonary veins and atrial sites. Furthermore, the results of neural recordings indicated that LL-VNS could inhibit the neural activity of GP, thereby suppressing AF [18]. Studies on ambulatory dogs by Shen et al [19] demonstrated that LL-VNS could inhibit left stellate ganglion (LSG) activity and reduce sympathetic nerve density in the LSG, thereby suppressing paroxysmal atrial tachyarrhythmias. These findings indicated that LL-VNS was both anticholinergic and antiadrenergic, which may account for its antiarrhythmic effects. Other studies also showed the anticholinergic and antiadrenergic effects of LL-VNS [20]. Moreover, if LL-VNS was initiated simultaneously with rapid atrial pacing, electrical remodeling such as shortening of ERP and increases in ERP dispersion could be prevented, indicating that if LL-VNS can be started immediately after AF initiation, atrial electrical remodeling may be prevented [21,22]. LL-VNS not only reversed atrial electrical remodeling but also suppressed autonomic remodeling [23]. Noninvasive LL-TS was demonstrated to reverse atrial electrical remodeling and inhibit AF inducibility in anesthetized dogs [24]. Preventing the loss of atrial connexin 40 and connexin 43 may be an important reason for the protective effects of LL-TS [25]. Moreover, LL-TS was demonstrated to play an important role in the acute stage of AF induced by obstructive sleep apnea [26]. LL-TS could significantly prolong atrial and ventricular ERP, decrease the window of vulnerability, and decrease the activity of the cardiac intrinsic and extrinsic nervous systems [26].