The Visible Heart® project and methodologies: novel use for studying cardiac monophasic action potentials and evaluating their underlying mechanisms

Schmidt, Megan; Iaizzo, Paul A.

doi:10.1080/17434440.2018.1493922

Cited by 6 publications

(2 citation statements)

References 62 publications

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“…These supplemental experiments were performed on a reanimated swine heart utilizing Visible Heart ® methodologies. Briefly, swine hearts were continuously perfused with a clear, modified Krebs-Henseleit buffer according to previously described methodologies [43, 44]. After providing a single 30 J shock, each heart elicited and sustained an intrinsic rhythm and associated hemodynamic function (more details in supplement).…”

Section: Methodsmentioning

confidence: 99%

HPC framework for in-silico trials on 3D virtual human cardiac population to assess drug-induced arrhythmic risk

Aguado-Sierra

Butakoff

Brigham

et al. 2021

Preprint

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Drug-induced arrhythmia continues to be a major health issue worldwide. The need for reliable pro-arrhythmic predictors became relevant during early phases of the SarsCoV2 pandemic, when it was uncertain whether the use of hydroxychloroquine (HCQ) and azithromycin (AZM) could be more harmful than beneficial due to their reported pro-arrhythmic effects.In this work we describe a computational framework that employs a gender-specific, in-silico cardiac population to assess cardiac drug-induced QT-prolongation after the administration of a single or a combination of potentially cardiotoxic drugs as HCQ and AZM. This novel computational methodology is capable of reproducing the complex behavior of the clinical electrocardiographic response to drug-induced arrhythmic risk, in-silico. Using high performance computing, the computational framework allows the estimation of the arrhythmic risk in a population, given a variety of doses of one or more drugs in a timely manner and providing markers that can be directly related to the clinical scenario. The pro-arrhythmic behavior observed in subjects within the in-silico trial, was also compared to supplemental in-vitro experiments on a reanimated swine hearts. Evidence of transmurally heterogeneous action potential prolongation after the administration of a large dose of HCQ was an observed mechanism of arrhythmia, both in the in-vitro and the in-silico model. The virtual clinical trial also provided remarkably similar results to recent published clinical data. In conclusion, the in-silico clinical trial on the cardiac population is capable of reproducing and providing evidence of the normal phenotype variants that produce distinct arrhythmogenic outcomes after the administration of one or various drugs.

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Section: Methodsmentioning

confidence: 99%

HPC framework for in-silico trials on 3D virtual human cardiac population to assess drug-induced arrhythmic risk

Aguado-Sierra

Butakoff

Brigham

et al. 2021

Preprint

Self Cite

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“…Moreover, it is an important means for observing the electrical activities of myocardial cells. 4,5 The action potential duration recorded by the synchronous recording technique for MAP is closely related to arrhythmia. 6 Acupuncture is a form of traditional Chinese medicine that has been used for more than 1000 years to relieve pain and treat various diseases including arrhythmia.…”

Section: Introductionmentioning

confidence: 99%

Effects of post-treatment electroacupuncture on ventricular monophasic action potential and cardiac function in a rat model of ischemia/reperfusion injury

Tang

Ren

et al. 2021

Acupunct Med

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Background: To determine the effects of post-treatment electroacupuncture (EA) on the electrophysiological properties of ventricular muscle in rats with ischemia/reperfusion (IR) injury. Methods: Male Sprague–Dawley (SD) rats were randomly assigned into sham-operated (SH), IR and IR + EA groups ( n = 8 each). The IR model was generated by ligation of the left anterior descending (LAD) coronary artery for 30 min. After establishing the IR model, EA was administered at PC6 for 30 min while opening the coronary artery and allowing reperfusion for 30 min. Heart rate (HR), mean arterial pressure and monophasic action potential (MAP) of cardiac muscle in the outer membrane of the antetheca of the left ventricle before coronary artery ligation ( T0), after coronary artery ligation for 30 min ( T1) and after reperfusion for 30 min ( T2) were recorded. At the same time, ventricular electrophysiological parameters including ventricular effective refractory period (ERP), conduction velocity (CV) and ventricular fibrillation threshold (VFT) were measured. Then, the cardiac function and the levels of creatine kinase-muscle/brain (CK-MB) and cardiac troponin I (cTnI) were monitored. Based on these data, monophasic action potential amplitude (MAPA), the maximum depolarization velocity ( Vmax) and the MAP durations at 50% and 90% repolarization (MAPD50 and MAPD90) were calculated to determine the incidence of arrhythmia during reperfusion. Results: Compared with the SH group, the IR group showed an obviously decreased HR as well as reduced mean arterial pressure, Vmax, CV, ERP and MAPA. All indices of cardiac function except left ventricular end-diastolic pressure (LVEDP) decreased (i.e. ventricular systolic pressure (LVSP), left ventricular ejection fraction (LVEF), fractional shortening (FS) and rate of the ventricular pressure rise/drop (±dp/dt)). Furthermore, the MAPD50 and MAPD90 were prolonged, and the levels of CK-MB and cTnI increased ( p < 0.05). In comparison to the IR group, HR and the mean arterial pressure were increased. All indices of cardiac function except LVEDP increased (LVSP, LVEF, FS and ±dp/dt). Vmax, CV, ERP and MAPA were also increased in the IR + EA group. However, MAPD50 and MAPD90 were distinctly shortened, and the levels of CK-MB and cTnI decreased ( p < 0.05). There were no statistically significant differences in VFT between the three groups ( p > 0.05). Conclusion: EA post-treatment can relieve prolongation of repolarization and slowed depolarization of ventricular muscle during IR, thus decreasing the rate of incidence of reperfusion arrhythmia.

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HPC Framework for Performing in Silico Trials Using a 3D Virtual Human Cardiac Population as Means to Assess Drug-Induced Arrhythmic Risk

Aguado-Sierra,

Brigham,

Baron

et al. 2023

Methods in Molecular Biology

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The Visible Heart® project and methodologies: novel use for studying cardiac monophasic action potentials and evaluating their underlying mechanisms

Cited by 6 publications

References 62 publications

HPC framework for in-silico trials on 3D virtual human cardiac population to assess drug-induced arrhythmic risk

HPC framework for in-silico trials on 3D virtual human cardiac population to assess drug-induced arrhythmic risk

Effects of post-treatment electroacupuncture on ventricular monophasic action potential and cardiac function in a rat model of ischemia/reperfusion injury

HPC Framework for Performing in Silico Trials Using a 3D Virtual Human Cardiac Population as Means to Assess Drug-Induced Arrhythmic Risk

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