Dr Lei Fan: Computational Modeling and the Working Heart

Dr Lei Fan looks at the heart as a whole, quantifying and modeling the mechanical forces acting upon it in each heartbeat. 

Focusing on cardiovascular disease, Lei and her team in The FAN Lab collect data from in-vivo and ex-vivo experiments and then model the data to see how disease develops, and how to best optimize treatments. 

However, Lei didn’t start out in cardiovascular research. Having completed her PhD in computational mechanics at Durham University, Lei began cardiovascular research as a postdoc. “I think the impact of cardiovascular diseases on individuals and communities sparked a deep curiosity in me,” Lei says, “I wanted to understand the underlying mechanisms and hopefully contribute to improving cardiovascular health.” 

That postdoc was highly collaborative, giving Lei the chance to work alongside other engineers and physiologists as she learned more about the heart and how best to collect the data she needed from it. “Those collaborations with other people definitely provided me with a lot of chances to see different technology, new experimental equipment, and other tools that I could use for my research,” Lei says, “that provided me with the chance to learn more about the Working Heart, which works well with my research.” 

an anatomical heart with arrows showing the perfusion pathway of a Working Heart model

Working Heart research is what it sounds like: studies that allow researchers to perform experiments on an isolated heart as though it were still working within the body. These require specialized equipment to isolate and perfuse the heart, ensuring that it is safe from environmental degradation and receiving the nutrients it requires to keep functioning throughout the experiments. 

Lei and her team added Working Heart studies recently, having previously used Langendorff and in-situ 

experiments to acquire the data needed for their computational models. She was drawn to Working Heart research as it is the most similar to heart function in-vivo. 

Related: Which Isolated Heart Study is right for you?

“I think compared to the Langendorff model experiments, in the Working Heart we can simulate the antegrade perfusion which is closer to the in-vivo beating heart in the human body,” Lei says, “That can provide us a chance to measure the pressure and volume when the heart is still beating.” 

This relative closeness to normal heart functioning allowed Lei and her team to focus on the impacts of single parameter changes, giving them the opportunity to better understand the effects of each single mechanism on broader cardiovascular function. 

“Compared to the in-vivo heart experiments, Working Heart [experiments] can really help us explain the effects of varying certain conditions.” Lei explains, “for example in the in-vivo measurements we couldn’t vary perfusion pressure, it’s very challenging. But in this Working Heart experiment we can vary the perfusion pressure by lifting up the tank bubbler, or we can also vary the preload/afterload conditions of the heart and then we can see how the pressure volume loop changes by varying those conditions. That can very much help us in understanding the mechanisms of the disease.” 

The process of acquiring data was also streamlined, compared to in-vivo experiments. “Rather than acquiring the pressure volume loop individually,” Lei says, “we can simultaneously acquire other data from the Working Heart apparatus. So, we can also look at perfusion pressure, heart rate, and ECG. So, together with the PV loops we can analyze how this complete set of data is affected by some of the different physiological or pathological conditions.” 

The more data she has to work with, the more complete


 Lei’s computational models become. The more complete her models become, the better able she and her team are to assess the impacts of different variables on cardiac function, and the ability for interventions to have an effect on that functioning. 

“As a researcher in the cardiovascular sciences, we have the opportunity to bridge the gap between the fundamental sciences to the translational applications in a clinical setting,” Lei says, “...it brings researchers closer to the real-world impact.” 

“I believe my research, by integrating the experimental and computational work, could provide some insight into the mechanisms of cardiovascular disease. Hopefully, the research findings from my work can help develop or optimize clinical therapies or medical devices to treat [future] heart failure patients.” 

Related: How Dr. Lei Fan improved confidence and efficiency in her cardiovascular research lab

Dr. Lei Fan

Lei Fan, Ph.D. 

Dr. Lei Fan is an Assistant Professor for the The Marquette University and Medical College of Wisconsin Joint Department of Biomedical Engineering and Director of The FAN Lab. Driven by her passion for integrating experimental and computational approaches in cardiovascular research, Dr. Lei Fan hopes to contribute to our greater understanding of cardiovascular diseases and ultimately improve the well-being of others.