Jim Kendrick

In Silico Modelling In Vitro Cardiomyocyte Assay

In Silico modelling of In Vitro Cardiomyocyte Assay has numerous advantages over the conventional method. Using the human ventricular AP model, it is possible to reproduce experimental data in an automated manner. This approach has the advantage of reproducing experiments for rate-dependent Ca2+ and intracellular sodium levels in undiseased human in silico model. Another advantage of this method is its high sensitivity to changes in intracellular potassium concentration (IKr).

The paper outlines the advantages and limitations of using this approach. The paper uses a computational model to simulate the electrophysiological activity of cardiac cells, which includes 20 ion channels and four ion pumps. This technique enables the quantitative description of drug effects on cardiac cell behavior. In addition, it enables a potential index of proarrhythmic risk. This method is also available for cardiovascular drug safety.

The first stage of the proposed harmonization work provides clarity on how to standardize assays and applies them to clinical assessment. The next step involves applying what we have learned to clinical trials. During this stage, a Q&A document will be developed. The project aims to be completed by June 2020. In addition, the project is expected to contribute to understanding the complex role of in silico models in clinical trials.

Despite its limitations, the results of the in vitro study are qualitatively consistent. Interestingly, the three models showed different susceptibility to drug-induced pro-arrhythmic events. Paci2020 induced the least number of pro-arrhythmic events, while Kernik2019 produced the most diverse variety of events and triggering mechanisms. The latter two models were also able to reproduce them in vitro repolarization failures, while Koivumaki2018 showed the most spontaneous activity.

The in vitro method combines a range of methods to investigate the mechanisms of cardiovascular disease. In silico models are often combined with preclinical in vitro pharmacological profiling, cardiomyocyte assays, and in vivo cardiovascular studies. One such strategy is a patient-specific hiPSC-CM. Using hiPSC-CMs as a screening tool, drug companies can test the effectiveness of different chemotherapy regimens on patients. Then, these models can be used to test whether a combination of treatments is safe.