Real science is hard. It’s time-consuming, expensive, and leads down many blind alleys. That’s one of the reasons pseudoscience is so alluring—anyone can do it. It doesn’t require an education, an R01 grant, or really even a grasp of reality.
So on to the current article. Heart disease is a big killer. Over half-a-million people yearly have the worst type of heart attack, called an ST-segment elevation myocardial infarction (STEMI). Coronary heart disease kills almost a half-a-million Americans yearly and around 300,000 people die of heart attacks in American ER’s every year.
So this is a pretty important disease. Here’s how it works…
An artery supplying blood to the heart may become suddenly unable to deliver enough blood to meet the heart muscle’s needs. This can be because of a sudden blockage of the vessel, or a narrowed vessel delivering a fixed amount of blood to a heart that suddenly needs more blood, for instance during exercise. When this happens, it hurts…bad…usually. The classic presentation of an STEMI is severe crushing chest pain often radiating to the left arm and neck, associated with sweating, shortness of breath, and a sense of impending doom. Sometimes this leads to sudden death, but when it doesn’t, time is muscle, meaning the sooner you can open the artery, the more heart muscle you can save from dying, and dead heart muscle is a bad thing. The blockage is usually opened either by injecting a clot-busting drug, or by inserting a catheter into the heart and opening the vessel with a balloon and bolstering it with a metal stent.
Time is muscle. Open the vessel. Get that blood to the muscle.
Except that when the vessel re-opens, and blood returns to the tissue (“reperfusion”), further injury can occur.
Reperfusion injury may account for up to half of the dead heart muscle left by a heart attack, but you can’t very well NOT open the artery. What to do?
We know some of the biochemistry behind this process. As blood reinfuses hypoxic tissue, toxic substances including free oxygen radicals are released. Also, an inflammatory response is set off as the immune system responds to dead or dying tissue. All this leads to killing heart cells that didn’t die from the original injury. Medical scientists, being pretty smart, have tried various free radical scavengers, anti-inflammatories, and other substances to try to reduce reperfusion injury, without good results. So more smarts were brought to bear.
It had been discovered in the laboratory that a final common event in cell death related to reperfusion is the opening of a pore in the membrane of mitochondria. This pore is called the “mitochondrial permeability-transfer pore”, but I’m sticking to “pore”. Mitochondria are the energy factories of cells, and when these pores are stuck open, all that good energy juice leaks out (OK, really, the membrane depolarizes leading to de-coupling of oxidative phosphorylation, the mitochondria become depleted of ATP and the cell dies—I’m sticking with “pore opens, cell dies”).
How does one close a pore whose diameter is the size of a few thousand atoms?
Another laboratory discovery found that a common immunosuppressant drug used to prevent organ transplant rejection and to treat other immune illnesses (cyclosporine) just happens to block that little pore.
Animal studies showed that this drug might help prevent reperfusion injury.
Some cardiologists in France decided to do a small pilot study on humans as a “proof-of-concept”; they asked if a dose of cyclosporine before opening the artery might help prevent reperfusion injury. By some measures, the drug seemed to reduce the area of injury.
I love science. Clinical problem meets basic science idea; idea is tested in lab, then in animal model. Then, idea is tested in small group of people to check for plausibility.
Next will probably be larger scale trials.
Science is hard, but it beats the alternative every time.
Piot, C., et al, . (2008). Effect of Cyclosporine on Reperfusion Injury in Acute Myocardial Infarction. New England Journal of Medicine, 359(5), 473-481.