New Treatment Lessens Heart Attack Damage

WEDNESDAY July 30, 2008 -- Giving the transplant drug cyclosporine to heart attack patients can prevent the injury that's caused by blood rushing back to the damaged heart, French researchers report.

The trial of cyclosporine involved 58 people whose blocked arteries were reopened after heart attacks. It was spurred by several lines of research, noted study lead author Dr. Michel Ovize, professor of physiology and cardiology at the University of Lyon.

One is the finding that some of the damage in heart attack survivors is caused by what is called reperfusion injury -- the unavoidable damage that comes when blood flow is suddenly restored to cardiac tissue through techniques such as balloon angioplasty.

"Recent studies, including some from our group, showed that tissue damage is due at least partially to the reopening of occluded arteries," Ovize explained. "This was new, because it was believed for a long time by doctors that all the damage was due to ischemia [blockage], not reperfusion."

Another line of research established that on the cellular level, damage was due to the opening of a structure called the "mitochondrial permeability-transition pore." Mitochondria are the energy-producing portions of living cells. "Research showed that the mitochondrial permeability-transition pore is a very important structure involved in cell death after [heart attack]," Ovize said.

And a third line of research showed that one of the unintended side effects of cyclosporine was to keep that pore closed. That activity has nothing to do with cyclosporine's use in organ transplants, the scientists said.

So, armed with those insights, the French tram treated half of the heart attack patients with an injection of cyclosporine just before the coronary arteries were reopened, while the other half got standard treatment.

Detailed studies showed that the amount of heart tissue that died was about a third less in people receiving the cyclosporine versus patients who did not get the drug.

Although the study is small and requires larger trials to confirm the finding, indications are that use of cyclosporine (or another drug with the same pore-blocking action) could reduce overall heart attack damage by 10 percent, said Derek M. Yellon, director of the Hatter Cardiovascular Institute at University College London, who wrote an accompanying editorial.

"People are going to do it when you are rushed to the hospital," he said. "You are in danger while they are reperfusing the muscle."

The reason for using a pore-blocking drug is "straightforward," Yellon said. "After a period of ischemia, when certain pores in the mitochondria open, that is detrimental," he said. "You'd rather keep those pores closed."

The French trial, Yellon acknowledged, is "a very small concept study. This area has not yet been well investigated."

"We are already involved in multicenter studies," Ovize said. Those studies will use not only cyclosporine, but also other pore-blocking agents. Drug companies are busily developing such agents, he said.

"In this study, by acting on the target, we were able to prevent cell death," Ovize said. "Now we need more studies to see whether that translates into improvement of left ventricular function and overall heart function."

More information

Current heart attack treatments are described by the U.S. Heart, Lung and Blood Institute.

Posted: July 2008


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