ATP levels can now be measured in living heart cells using the protein luciferase, which is naturally found in the tails of fireflies. Luciferase lights up in the presence of ATP, which is what causes the tail to glow, since fireflies use ATP to power flight. By transferring luciferase into heart cells which then ‘light up’, the levels of ATP can be observed and the mechanisms controlling its production determined.
The light is recorded using a micro-scope and a highly sensitive camera. Conditions causing oxygen deprivation to the heart, like angina, coronary heart disease and also cardiac surgery, prevent enough ATP being made. Even worse, when the blood flow to the deprived (ischaemic) heart is restored, mitochondria can change from being energy providers to killers that cause irreversible damage to the heart. Research directed towards elucidating the mechanism responsible for this ‘Jekyll to Hyde’ change in the behaviour of mitochondria aims to develop ways of preventing it occurring. Some of the drugs that do this now show potential for use during cardiac surgery.
The energy solution
During open heart surgery, blood is diverted away from the heart using a bypass machine that keeps blood pumping around the rest of the body, but this can damage the heart muscle. To minimise this damage, cardioplegic solutions are infused into the heart that stop the heart beating, both saving its energy and allowing surgeons to operate on it.
Research has shown that supplementing the cardioplegic solutions with agents that preserve the heart’s ATP supply can also protect the heart during surgery. This was demonstrated by collecting (very small) heart muscle biopsies and blood samples during surgery. These samples were used to measure the ATP reserves in heart cells, as well as proteins that are released from the heart into the blood when heart cells die. Monitoring these markers enabled the design of improved cardioplegic solutions, including use of warm solutions (cold solutions had previously been used), and solutions supplemented with blood. Another finding was that the solutions had to be designer-made for different age groups and different types of heart disease. A challenge facing paediatric surgeons is the small size of children’s hearts, so they need optimum protection during surgery. As one surgeon put it: “These significant improvements for patients undergoing heart surgery are an excellent example of how basic science and clinical research can complement each other to change clinical practice.”