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The true profile of ICl(Ca) during an actual ventricular action potential (AP), however, is poorly understood.
We examine the problem of parameter estimation in mathematical models of excitable cell cardiac electrical activity using the well-known Beeler Reuter (1977) ionic equations for the ventricular action potential.
The performance of the proposed method is tested using the Luo-Rudy phase 1 (LR1), dynamic (LR2), and human O'Hara-Rudy dynamic (ORd) ventricular action potential models, and the Courtemanche atrial model incorporating a Markov sodium channel model.
Indeed, it is likely that most native ventricular Kv channels exhibit temporal and spatial heterogeneity of subunit composition, complicating both modeling of their functional impact on the ventricular action potential and design of specific current-targeted compounds.
Pharmacologic therapy is designed to produce an inward shift in the balance of currents active during the early phases of the right ventricular action potential (AP) and can be used to abort electrical storms or as an adjunct or alternative to device therapy when use of an implantable cardioverter defibrillator is not possible.
Also, the effects of dexmedetomidine on the ventricular action potential were evaluated in enzymatically isolated ventricular myocytes.
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To rectify this issue, the Comprehensive in vitro proarrhythmia assay (CiPA) initiative has been proposed to integrate drug effects on multiple cardiac ionic currents with in silico modelling of human ventricular action potentials, and in vitro data obtained from human stem cell-derived ventricular cardiomyocytes to estimate proarrhythmic risk of new drugs with improved accuracy.
The concomitant 2∶1 heart block was very likely caused by conduction block in the ventricle due to extremely prolonged ventricular action potentials, similar to the suggested mechanism of 2∶1 heart block caused by another SCN5A mutation in a newborn[24].
The decrease in INa induced a moderate (11 15%) non-significant decrease in maximum upstroke velocity (Vmax) of ventricular action potentials in Scn5a+/− mice with mild conduction defects (Figure 8).
Stress and catecholamines suppress arrhythmias in vivo and shorten ventricular action potentials in this model.
β-Adrenoceptor-blockade by esmolol caused lengthening of ventricular action potentials.
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