Implantable cardioverter-defibrillators are the best solution to a number of electrical problems with the heart, and result in a measurable improvement in quality and length of life for those that need them. However, a recent study entitled Evaluation of Early Complications Related to De Novo Cardioverter Defibrillator Implantation in the Journal of the American College of Cardiology found that (as summarized here), “4.1 per cent of patients experienced major complications … within 45 days of device implant and they had more than three times the risk of dying within the next 6 months.” It was also noted that the likelihood of complications in women was higher.

The study also found that more complicated devices were a strong predictor of complications. It was noted in the study that patients with more complex and severe problems typically require the more complex devices, making it difficult to ascertain whether the patients’ health or the devices were at fault. I can understand the motivation of the authors in choosing the wording of their conclusion, but I wonder if maybe it sounds a bit too certain without the caveats written in the article. They concluded, “Complications after de novo defibrillator implantation were strongly associated with device type. Major complications were associated with increased risk of mortality.”

The authors of ionic models (see also the list of ionic models we currently offer) are typically wet-lab savvy — they patch-clamp cells and run special experiments on them, stepping voltage up and down and whatnot, to understand the behavior of the ion channels in the cell’s membrane. They then assemble what they learn into a system of ordinary differential equations using Hodgkin-Huxley and Markov network formulations. These systems may be solved using a number of methods to reproduce with some degree of accuracy the electrical (and electrochemical) processes that take place in such a cell.

A number of methods for publishing ionic models exist, as highlighted in a recent discussion in the Cardiac Simulation LinkedIn group. Sergey mentions in particular MIRIAM and CellML. Our own Rob Blake has highlighted some of the pros of CellML on this blog. I must prod him to highlight also the significant cons. The most basic methods of ionic model publication are the inclusion of variables and equations in papers, and the publication of original code. For an example of how the equations and variables are normally published, have a look at the Luo and Rudy Dynamic (II) model (PDF) paper, starting on page 16, in the Appendix. Alternatively, Kirsten ten Tusscher has published C++ source code for her models. We have used that source code, for example, to thoroughly validate our TT and TT2 models.

I am generally a proponent of the publication of working ionic model code, specifically that used for the plots and other output in the corresponding publication. As any scientist who has ever written code and published something related knows, by the time the relevant paper is published you will have forgotten much of the details around running your own code. If you ‘clean it up’ a bit and post a single, supposedly-final version of your code with the article, it’s quite likely something will be off a bit from the ‘live’ code you used while writing the paper. But even that is better than trying to go back and extract the equations from the code after you’ve got everything working correctly. The wonderful thing about having such code available is that it’s possible to test new implementations against the original under all sorts of conditions, including disease conditions (for example, hyperkalemia) and extremely long run-times.

Have you published an ionic model? How do you feel about publishing code? CellML models? Equations? Have you ever tried to reimplement an ionic model from a paper? From a CellML model? How did it go?

I’m happy to say that some of the questions I posted on the Cardiac Simulation LinkedIn group have garnered some answers. In particular, the discussions about modeling tools for cardiac simulation and source code access have had some traffic from the developer of CESE and CESE Plus. We’d love to get your opinion on those and other subjects — come sign up! Elizabeth Lipke and Xiao Jie have recently joined the group.

Most of the modern meshing done by CardioSolv and its members is done using a software package called Tarantula. It was used in many of the publications listed on this site. We are now happy to announce that through a partnership with CAE Software Solutions, we sell and support the Tarantula package. It is an excellent companion to our CARP solver, enabling the creation and use of realistic models from medical images. For more information on Tarantula, please see the Tarantula page on CAE’s site.