It’s humbling to see medical dogma overturned, but that is precisely what happened when contrary to deeply embedded thought, scientists led by Jonas Frisen from the Karolinska Institute in Stockholm reported in Science today that the heart can grow new muscle cells, and does so regularly, albeit slowly, in the course of a lifetime.
To cardiologists, this is a blockbuster discovery, since the heart has been pegged as a disadvantaged organ in terms of injury, healing, and repair. Susceptible to coronary blockages that can cut off blood and destroy more massive hunks of heart muscle at one time in a heart attack, the heart can only heal itself slowly, often leaving behind thinned and baggy scar tissue devoid of healthy, beating muscle. And the distortion and remodelling of the heart that comes with this muscle loss set the patient up for cardiac failure, blood clots, and nasty heart rhythms. It was always assumed the heart could do no better. But that does not seem to be so.
The clever piece of work from Sweden used carbon dating to figure out the age of human heart cells. The spike in the concentration of atmospheric radioactive carbon-14 triggered by above-ground Cold War nuclear tests between 1955 and 1963 allowed the researchers (with the help of physicists and sophisticated mass spectrometry from the Lawrence Livermore National Laboratory in California) to discover that, lo and behold, the heart has slow and silent regenerative abilities. The evidence: the many heart cells whose nuclei—which last the life of the cell—had radioactive carbon levels that coincided with the atmospheric spikes, occurring many years after the person was born. The study found that younger adults renew about 1 percent of their heart cells per year. The growth falls off to roughly half of that in the elderly.
This is no abstract, ho-hum science factoid. It makes incredible sense of something that has always puzzled me: If hearts can’t make new heart tissue, why did ever efficient Mother Nature gives them to stem cells? Yes, for years, scientists have known that adult stem cells can be found in the heart. This has prompted numerous centres in many countries to pursue stem cell therapeutics in patients with heart attacks, heart failure, and even severe angina to repair muscle and improve blood supply.
The work looks more than promising. In several studies, using cocktails of patients’ own bone marrow stem cells, which can be sifted out of the bloodstream and infused back into the patients in a concentrated and enriched form, has produced better-than-expected heart function and blood flow. (Adult stem cells circulating in the blood are known repairmen that can hone in on injured tissue anywhere in the body.) Recent studies in rats have gone so far as to create a matrix for these cells to grow on that can become a healthy-looking, growing and beating tissue graft after being implanted in a damaged heart wall.
The work is moving fast and furiously to make stem cell technology a standard part of cardiac care. Even the greatest sceptics have taken note. The Cochrane Collaboration, a well-respected international group that assesses the latest technology with a very tough eye, concluded late last year that, based on its review of reports involving over 800 patients from several centres, stem cell infusions after heart attacks had shown some definite benefits. To be sure, more work needs to be done, though.
Smart medicine honours the rules of the human body as best they can be determined. For example, a sturdy immune system fights off most microbes we encounter; and vaccines and antibiotics work because they complement that already finely tuned inborn system. The discovery that the wounded heart can renew itself over time, giving the reason for the naturally occurring stem cells found in its muscle, provides great encouragement that harnessing and accelerating the body’s own regenerative capacity will become a powerful technology in the not-too-distant future.
Scott Ouellette had a massive heart attack at age 28.
It left him with a heart so damaged that he needed a battery-powered device surgically implanted in his chest, to keep his blood circulating while he waited for a heart transplant.
Dr. Paul Fedak is the surgeon who implanted that device in Scott’s chest. But one day, if his research is successful, Dr. Fedak hopes patients with advanced heart failure like Scott won’t have to resort to transplants as the last hope to replace their damaged hearts.
He wants to use the body’s own cells to help a damaged heart heal itself.
“There are not – and there will never be – enough donor hearts to treat all the people with advanced heart failure,” says Dr. Fedak, a cardiac surgeon and Heart and Stroke Foundation researcher specializing in heart failure. Less than 200 heart transplants are performed each year in Canada. That’s why he’s passionate about finding another solution. Dr. Fedak believes that regenerative medicine holds the greatest potential to help patients like Scott.
When heart failure strikes
Heart failure occurs when the heart is damaged from a heart attack or other cause, leaving it unable to pump blood through the body as well as it should. While there are treatments to manage the symptoms, there is no cure. It is a long-term chronic condition that gets worse over time. Today, 600,000 Canadians are living with heart failure, and 50,000 more are diagnosed every year.
“Heart failure is reaching epidemic proportions in North America,” says Dr. Fedak.
So the impact of regenerative medicine could be enormous. “It’s about taking cells in your body that could turn into new heart muscle or help repair your damaged heart,” he says. “Your body has the capacity to heal the heart. We used to think that it didn’t, but we now know that your heart can heal itself.”
Coronary artery disease can block arteries, damage or kill part of your heart muscle and weaken your heart’s function. But what if the muscle that seems dead is only dormant or asleep and there’s a way to “wake it up”?
For some patients, when disease reduces blood flow to parts of the heart, the muscle doesn’t die.
It goes into sleep mode, as though it’s waiting for conditions to improve. This condition is known as hibernating myocardium (heart muscle), says cardiologist Wael Jaber, MD.
You can live with coronary artery disease, but it reduces your heart’s function. When heart muscle dies, scar tissue typically forms in the area.
If the muscle is only dormant, however, doctors can try to restore blood flow by reopening your artery, reviving the muscle and strengthening your heart’s function, Dr. Jaber says.
Repairing a damaged heart
Dr. Fedak’s research, with funding from the Heart and Stroke Foundation, is looking at repairing damaged tissues in the heart muscle after a heart attack. “My research involves a biologic material – an organic patch – that we can sew on the surface of the heart, at the place where the heart muscle is damaged.” This patch sends signals down into the muscle after a heart attack to stimulate the development of new blood vessels.
“As a surgeon, I can do a coronary bypass and create a big blood vessel, but I can’t create those little tiny blood vessels that need to get into the deep areas of the muscle to help repair it. We’ve got some really exciting data, it’s all fitting together, and it’s got a lot of potentials,” he explains.
Dr. Fedak’s research could be a game-changer for patients with heart failure. He and his team have been working for about 10 years to better understand how this organic patch can function best, and now they are close to translating this therapy into patients.
As for Scott Ouellette, he waited 113 days with that device in his chest, until finally, the call came that a donor heart was waiting for him. Today he and his family are enjoying life to the fullest, and are grateful every day for the research and medical expertise that saved his life.
Your skeletal muscles can repair themselves after an injury — pull your calf muscle and, after a few days or so, it heals. Until recently, it was believed that the human heart didn’t have this capacity. But the heart does have some ability to make new muscle and possibly repair itself. The rate of regeneration is so slow, though, that it can’t fix the kind of damage caused by a heart attack. That’s why the rapid healing that follows a heart attack creates scar tissue in place of working muscle tissue.
Walking (and other forms of aerobic exercise) after a heart attack does several things. It strengthens the remaining heart muscle. It keeps your arteries flexible, which makes it easier for your heart to pump blood through the thousands of miles of the circulatory system. It also helps fight atherosclerosis, the process that most likely led to your heart attack. This is crucial because it is not the heart attack you just had that you should worry about — it is preventing the next one. Exercising five times a week is a great way to do this.
Heart muscle is one of the least renewable tissues in the body, which is one of the reasons that heart disease is the leading cause of death for both men and women in the United States, according to the Centers for Disease Control and Prevention. Inspired by the idea of helping the heart repair itself, researchers at Baylor College of Medicine and the Texas Heart Institute have studied pathways known to be involved in heart cell functions and discovered a previously unknown connection between processes that keep the heart from repairing itself. This finding, published in the journal Nature, opens the possibility of developing strategies that will promote heart cell renewal in the future.
“We are investigating the question of why the heart muscle doesn’t renew,” said senior author Dr. James Martin, professor and Vivian L. Smith Chair in Regenerative Medicine at Baylor College of Medicine. “In this study, we focused on two pathways of cardiomyocytes or heart cells; the Hippo pathway, which is involved in stopping renewal of adult cardiomyocytes, and the dystrophin-glycoprotein complex (DGC) pathway, essential for cardiomyocyte normal functions.
We are also interested in studying mutations in DGC components because patients with these mutations have a muscle-wasting disease called muscular dystrophy.
Previous work had hinted that components of the DGC pathway might somehow interact with members of the Hippo pathway. In this study, Martin and colleagues studied the consequences of this interaction in animal models. The researchers genetically engineered mice to lack genes involved in one or both pathways, and then determined the ability of the heart to repair an injury. These studies showed for the first time that dystroglycan 1, a component of the DGC pathway, directly binds to Yap, a part of the Hippo pathway and that this interaction inhibited cardiomyocyte proliferation.
“The discovery that the Hippo and the DGC pathways connect in the cardiomyocyte and that together they act as ‘brakes’ or stop signals to cell proliferation opens the possibility that by disrupting this interaction one day it might be possible to help adult cardiomyocytes proliferate and heal injuries caused by a heart attack, for example,” Martin said.Another long-term application of this discovery could be to improve cardiac function in children with muscular dystrophy.
“Patients with muscular dystrophy can have a severe reduction in cardiac function,” Martin said. “Our findings may help to design medicines to slow down the cardiac decline in muscular dystrophy by stimulating cardiomyocyte proliferation. In order to do that, we need more research to understand cardiomyocyte growth control pathways in greater detail.”
Making simple changes in what you eat, how often you exercise, how much you weigh, and how you manage stress can help put the brakes on heart disease.
But can you actually reverse it, not just slow it down?
You can undo some, but probably not all, of the damage. You’ll have to make big, lasting changes to your lifestyle.
Having a bad heart doesn’t mean you can skip exercise, doctors said Wednesday. In fact, it may even help your heart to repair itself. Research presented at the European Society of Cardiology meeting showed that exercise sparks the creation of new heart vessels.
In a small study of 37 people at Leipzig University in Germany, Dr. Robert Hollriegel found that people with serious heart failure who rode a bike for up to 30 minutes a day for four months produced new stem cells in their bones.
They also had more small blood vessels in their muscles. Those who didn’t exercise had no change in their vessels or muscles.
Most patients with heart failure are over 70 years old, and some can barely walk a few steps without stopping for rest. Doctors think that even these patients would benefit from light exercises such as walking or cycling. To ensure that patients will be able to handle a certain level of physical activity, doctors conduct a test first to determine their maximum limits and to ensure they would not be exceeded. Some exercise regimens also are supervised by health professionals.
“We’re not talking about patients with acute heart problems,” said Dr. John Cleland, a heart failure specialist at the University of Hull in Britain. The latter is the spokesman for the European Society of Cardiology. Cleland was not involved in Hollriegel’s research.
“This is to prevent people from getting into a cycle of deterioration where they’re afraid to exercise, and they just avoid any activity that leaves them out of breath,” he said.
Physical activity strains the heart’s arteries and muscles by sending ten times the normal amount of blood to the muscles being used. Stem cells then are dispatched to relieve this stress and may repair any damaged parts. If you continue to exercise, these stem cells help the body adapt to the pressure, by building new blood vessels and strengthening muscles. But to maintain such benefits, you must exercise regularly.
Yes, You Can!
Dean Ornish, MD, founder and president of the Preventive Medicine Research Institute, has written six best-selling books, including Dr Dean Ornish’s Program for Reversing Heart Disease.
In his book The Spectrum, Ornish describes patients waiting to undergo a heart transplant — those with the worst possible damage — who enrolled in his program while on a transplant list. Some of them, he says, improved so much, they no longer needed a transplant.
“Our studies show that with significant lifestyle changes, blood flow to the heart and its ability to pump normally improve in less than a month, and the frequency of chest pains fell by 90% in that time,” Ornish says.
“Within a year on our program, even severely blocked arteries in the heart became less blocked, and there was even more reversal after five years. That’s compared with … other patients in our study, in which the heart just got worse and worse.”
You know your heart muscle is working well when it’s contracting with each beat and getting good blood flow from the arteries.
Once disease reduces blood flow, your heart muscle may hibernate. It reduces its function to the point where it’s barely keeping itself alive.
Your cardiologist can try to restore blood flow and get your heart muscle back to more normal functioning through bypass surgery or by using a stent to open up the artery.
However, Dr. Jaber notes that it’s difficult to distinguish between the dead heart muscle and hibernating muscle because there is little or no blood flow in the area.
A hibernating muscle is like a sleeping bear in the middle of winter. They slow their heart rate and respiration. They slow everything. If you look at a dead bear and a hibernating bear, it’s difficult to tell the difference.
If your heart muscle is dead, restoring blood flow will not help.
“We want to make sure first before we open the artery whether the muscle is dead or alive,” Dr. Jaber says. “If you’re trying to reopen an artery to a dead muscle, you’re not doing the patient any favour.”