A research team at Tufts University in the US have successfully created a tiny, “microfluidic chip” which is able to mimic what happens to heart cells following a heart attack, and after a blocked artery is reversed.
“Heart-on-a-chip models are a powerful tool to model diseases, but current tools to study electrophysiology in those systems are somewhat lacking, as they are either difficult to multiplex or eventually cause damage to the cells,” says Brian Timko, correspondent author of the study published at Nano Letters.
The team was led by biomedical engineers from around the world who together searched for what happens in cells following cardiovascular disease. Cardiovascular disease is an umbrella term for conditions affecting the heart or blood vessels. It usually starts with a build-up of fat inside arteries which narrows the blood vessels and makes them more prone to blood clots. Most patients with this disease feel complications due to ischaemia, which is when an organ loses blood supply due to a blocked artery and is therefore starved of oxygen. This can result in organ failure which could cause a heart attack.
The heart inside a chip
A microfluidic chip is exactly what it sounds like – a tiny chip with a layer of fluid on top. Under the fluid, there is a layer of heart cells which are embedded onto the surface of the chip, like on a bed of nails. These ‘nails’ puncture through the cell surface and measure changes in voltage. Cells have changeable voltages. A rapid change in voltage from negative to positive reflects a phenomenon known as an action potential. Scientists can study action potentials to determine the “excitability” of cells, that is, how likely they are to send a message, for example, from one neurone to the next. In the case of the heart, the rate of action potentials firing determines the rate at which the heart beats. In this case, cells must communicate with each other properly to keep a steady heartbeat.
Why use a chip?
Scientists wanted to understand what could cause irregular heartbeats on the chip they developed, and how this heartbeat changes after treatment. To do this, they had to find a way to change oxygen levels around the cardiac cells.
Firstly, scientists mimicked the heart in low oxygen concentrations. The chip had many vessels and tubes poking into it, through which different fluids could travel in and out. The scientists bathed the cells in fluid with a low oxygen concentration and found that the electrodes picked up more frequent action potentials. In the human body, this would have caused the heart to beat rapidly and result in tachycardia (a heart rate of over 100 beats per minute). The action potentials eventually slowed and stopped, as is seen with heartbeat frequency during a heart attack.
Secondly, researchers wanted to understand what happens to cells in the heart after treatment, when the artery is unblocked. Since treatment unblocked the arteries, blood could flow to the affected site, and with it comes a rush of oxygen. Scientists reintroduced fluid with a normal level of oxygen and saw that they could bring back standard rhythmic waves. This means that five-and-a-half hours after a heart attack, it is theoretically possible to reinstate a completely normal heartbeat.
The next step for the researchers is to figure out how to apply this information to future therapies.
“In the future, we can look beyond the effects of hypoxia and consider other factors contributing to acute heart disease,” said Brian Timko.
Cardiovascular diseases are the leading causes of death worldwide. Thus, researching and understanding what happens inside heart cells during a heart attack could be key to develop more efficient drugs, and it could all start with a chip.