FOR years doctors have been frustrated by the fact that they lacked any way of repairing heart tissue in patients who鈥檇 had heart attacks. Now, that tantalising possibility has moved one step closer with the discovery that rats can make almost a full recovery after a simulated heart attack.
鈥淭his is a dramatic recovery,鈥� says study leader Felix Engel, who works at the Children鈥檚 Hospital in Boston, Massachusetts. 鈥淎 human with this kind of heart muscle damage would be dead.鈥�
鈥淭his is a dramatic recovery. A human with this kind of heart muscle damage would be dead鈥�
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Ordinarily, when blood flow is prevented from reaching the heart during a heart attack the tissue dies, forming irreparable scar tissue. This can impair the heart鈥檚 ability to pump blood or cause life-threatening abnormal heart rhythms, or arrhythmias.
Engel and his colleagues found that they could trigger regrowth in the damaged areas of the rats鈥� hearts by injecting two drugs: a p38 MAP kinase inhibitor that promotes cell division within the heart, and fibroblast growth factor 1 (FGF1), which encourages blood vessel growth.
Building on a previous study that grew new heart muscle cells in a Petri dish, the researchers simulated heart attacks in rats by permanently tying off one of their coronary arteries. Three months later, the hearts of those rats that had had simulated heart attacks and received both drugs immediately afterwards pumped almost as well as the hearts of uninjured rats. There was also less thinning of the cardiac wall and scarring in their hearts (see Diagram) (Proceedings of the National Academy of Sciences, DOI: 10.1073_pnas.0607382103).
鈥淭he bottom line of this study is great,鈥� says Yibin Wang, a medicine and physiology professor at the University of California, Los Angeles, who worked with Engel on the initial cell culture study. 鈥淭hey have found a way to break the barrier of cardiac regeneration.鈥�
However, Wang questions whether the benefits observed in the study were purely down to regeneration. In the rats that had had simulated heart attacks and were given the drugs, heart function began to increase just a day afterwards 鈥� too soon, in his opinion, for the recovery to be attributed to the drugs stimulating cell division and blood vessel growth. He suspects that the damaged cells never died, but were protected by the drugs.
Wang would like to see follow-up studies in which the drugs are given a week or more after an attack, a more realistic situation for patients who do not realise that they have suffered from a mild heart attack until days, or even weeks, later. 鈥淚f they can show that it works on a previously damaged heart, that would bring this treatment from the bench to the bedside,鈥� he says.
鈥淚f they can show that it works on a previously damaged heart, that would bring this treatment from the bench to the bedside鈥�
The researchers may also have to find a way to deliver the drugs directly to a patient鈥檚 heart, as they could cause liver damage or promote potentially cancerous growths in other parts of the body if they went astray. Techniques could include using a catheter to transport the drugs to the damaged areas, or applying a slow-release gel directly to the heart.
In recent years, stem cell therapy 鈥� in which highly versatile cells are harvested from embryos or from the patients themselves and then manipulated into becoming new tissue 鈥� had been considered the most promising way of some day regrowing damaged heart tissue.
鈥淲e are still in the very beginning stages, but I think we have enough evidence to say this is a promising alternative,鈥� says Engel.
