Out of Rhythm

It happens 300,000 times each year. Suddenly, often without warning signs, an apparently healthy American dies when a storm of electrical activity overwhelms the heart and stops it from beating. Doctors call it ventricular fibrillation, and it is the leading cause of sudden cardiac death.

Another 2.2 million Americans live with a related heart rhythm disorder, or arrhythmia, called atrial fibrillation. AF can be just as dangerous, because it increases the risk of developing blood clots in the heart and having a stroke.

All cardiac arrhythmias are triggered by disturbances in waves of electrical activity that pass through the heart. These electrical impulses stimulate billions of cardiac muscle cells to beat together in a coordinated rhythm. The problem is that scientists still don’t know exactly what causes these electrical disturbances.

The arrival at Michigan of a multi-disciplinary team of researchers from the SUNY Upstate Medical University in Syracuse, New York, could change that. Led by José Jalife, M.D., and Mario Delmar, M.D., Ph.D., 35 SUNY scientists and technicians are joining the Cardiovascular Center to create a new Center for Arrhythmia Research.

“Fibrillation is like a tornado in your heart muscle, except instead of wind, it’s made up of electrical waves,” says Jalife, the Cyrus and Jane Farrehi Professor of Cardiovascular Medicine.

Jalife and Delmar are well-known for their basic scientific work on the underlying cause of cardiac arrhythmias, but Jalife says they needed to be part of an institution with a strong clinical program to transfer their research findings from the lab to the clinic. So the opportunity to collaborate with U-M physicians like Hakan Oral, M.D., and Fred Morady, M.D., was a big reason why they decided to become part of the Cardiovascular Center.

“We have one simple goal and that is to cure arrhythmia,” says Oral, the Frederick G.L. Huetwell Research Professor of Cardiovascular Medicine. “Achieving that goal requires a multidisciplinary approach with basic scientists and clinicians focusing on the problem from different perspectives.”

Oral and Morady, the McKay Professor of Cardiovascular Disease, are leaders in the use of radiofrequency ablation to treat complex arrhythmias.

“Every cell in the heart is capable of twitching. The trick is you want them to twitch at the same time in synchrony,” says Delmar, the Frank Norman Wilson Professor of Cardiovascular Medicine.

To study atrial and ventricular fibrillation, Jalife and his colleagues developed technology that measures the precise frequency interval between heartbeats at specific locations within a patient’s heart.

“Our hypothesis is that areas with the fastest frequencies are where the vortices that maintain fibrillation are located,” Jalife says.

“The collaboration will benefit not only our patients, but patients with heart rhythm disturbances everywhere,” says David Pinsky, M.D., a director of the Cardiovascular Center. —SP

More on Arrhythmia Research
Patient information on atrial fibrillation

Non-Stop Noise

About 50 million Americans, especially aging baby boomers and military veterans, have forgotten what it’s like to hear the sounds of silence. They live with constant noise caused by a condition called tinnitus. For some, it’s a high-pitched whine, while others hear a low hum or the sound of ocean waves.

Tinnitus is a common side effect of age-related hearing loss or inner ear damage caused by exposure to loud noises. Trauma to the head or neck — even dental work — can trigger tinnitus. Physicians don’t understand exactly what causes it, and have few ideas about how to make it stop.

Susan Shore, Ph.D., a research professor in otolaryngology and an associate professor in molecular and integrative physiology, suspects the brain’s response to hyperactive trigeminal nerves in the face and neck plays a role in the development of tinnitus. Shore compared neural activity in deaf and normal guinea pigs and found that sensory-sending nerves respond to hearing loss by ramping up their activity in the brain. —SP

An expanded version of the story
Hear what tinnitus sounds like

Drop the Belly Fat

Most physicians agree that an overweight patient who carries excess fat around her stomach has a higher risk of heart attack and stroke than a patient whose fat is concentrated in her hips and thighs. But why is still a medical mystery.

In an attempt to solve the mystery, Daniel Eitzman, M.D., an associate professor of internal medicine at the U-M and the VA Ann Arbor Healthcare System, is studying obese mice. These mice are fat because they lack the gene for leptin — a hormone produced by fat cells that helps control appetite and metabolism. When Miina Öhman, M.D., Ph.D., a postdoctoral fellow, transplanted fat tissue from normal mice into leptin-deficient mice, they started producing leptin and lost weight. But Eitzman and Öhman were surprised to see signs of chronic inflammation, including immune cells called macrophages, surrounding the transplanted fat cells.

Inflammation is the immune system’s way of defending the body against infection or injury. While targeted inflammation is a good thing, uncontrolled or chronic inflammation can do a lot of damage to healthy tissue. Using a strain of mice that develop high cholesterol and atherosclerosis, Eitzman and other scientists conducted a series of experiments to identify the relationship between atherosclerosis and inflammation in fat.

The answer turned out to be the type of fat the mice received. Mice with transplants of abdominal fat developed inflammation and atherosclerosis. Mice given transplants of subcutaneous fat — the kind found under the skin throughout the body — had inflammation, but no atherosclerosis.

Eitzman believes some interaction between cells involved in inflammation and abdominal fat cells could be triggering the development of atherosclerosis. In future research, he hopes to figure out exactly what happens and how to prevent it. In the meantime, he says eating a balanced diet and exercising to lose excess fat, especially abdominal fat, is still the best way to reduce your risk of heart disease associated with obesity. —SP

More on inflammation and abdominal fat
Patient information on cardiovascular disease