Health Sciences Research

Two researchers, one heart

How does one describe the amazing machine that is the human heart? What’s the most appropriate adjective to use? On a gray afternoon this winter, in the airy offices of the Center for Translational Research and Education (CTRE) on Loyola’s Health Sciences Campus, Seth Robia, PhD, and Jonathan Kirk, PhD—professors in Loyola’s department of Cell and Molecular Physiology—batted around some ideas. A month prior, Robia had been named the St. Albert’s Day Senior Scientist of the Year and Kirk named the St. Albert’s Day Junior Scientist of the Year for their research into the mechanics of the heart. Each has made it his professional mission to understand exactly how the organ runs and how to ensure that it keeps running for as many people as possible.

“The heart never gets a chance to rest,” Robia said. “It’s beating 70 beats per minute, every minute.”

From across the desk, Kirk jumped in: “And from an energetic standpoint, a person only ever has enough energy to last three beats or so. Then it’s gone. You’re basically operating on the edge for the entirety of your life.”

 A healthy heart pumps enough blood to fill a bathtub every hour, an Olympic-sized swimming pool every year. It weighs just 11 ounces. The workload, in other words, is formidable. Robia looked up at the ceiling, searching for the right modifier. “If you think about how force is generated by this mushy bag, it’s quite amazing,” he said. “It’s a dynamic muscle, for sure. But it’s very…delicate.”

Kirk couldn’t believe his ears. “Delicate? That makes it sound weak!”

“No, no, no—I mean delicate like a Porsche engine! Finely-tuned.”

“I’ll definitely give you that.”

Because of that delicacy, it’s not surprising that the heart often malfunctions, especially as we age. Some 5 million Americans currently live with congestive heart failure (CHF); symptoms include chest pressure or pain, palpitations, shortness of breath, fatigue, swelling. More than half of people who develop CHF die within five years of their diagnosis. Indeed, heart disease kills more Americans than all forms of cancer combined.

Controlling the motor

Kirk trained as a biological engineer, and he approaches his research with an eye towards structure. (“I’m not as big a fan of squishy stuff,” he said. “My cells are like bricks, perfectly organized.”) On his desktop monitor, otherwise peppered with Post-It notes, Kirk queued up a slide. The title was “Cardiac Myofilament.” Underneath sat a black-and-white photo of a strangely beautiful patchwork. It looked geometric, almost crystalline.

That protein lattice, magnified for the screen, is the instrument that allows heart cells (or myocytes) to contract, producing the force that keeps blood moving. His lab—with the assistance of mass spectrometers and other sophisticated equipment—measures force production at infinitesimal scales. It’s all in an attempt to understand what causes that myofilament to malfunction on the molecular level. The heart, in Kirk’s eyes, resembles a motor. In some cars, that motor has been run too hard for too long. “You’ve got duty cycles and energy costs,” he said. “It lends itself very well to an engineer’s type of thinking.”

11 ounces

Approximate weight of the human heart

360 liters

Amount of blood the heart pumps hourly

5.7 million

Number of Americans affected by heart failure

If Kirk studies the motor, Robia’s lab focuses on the control of that motor. Specifically, the tiny proteins that move ions (sodium, calcium) around individual heart cells, prompting those cells to contract or relax, thereby generating the energy needed to squirt blood toward the body’s far-flung corners. (He calls it “the trigger for cranking up that power.”) The ultimate goal is to figure out how the heart muscle responds to the varying demands of exercise and rest, and how the cells inside become disordered when disease takes hold. Those cellular movements and machinations are largely a mystery, even decades after the embedded proteins were initially identified.

To investigate, Robia and his colleagues employ “typical white lab coat biochemistry,” spreading proteins on gels to “see what size they are and how they change.” Using fluorescence, they also run biophysical experiments, engineering special proteins that light up when blasted with high-intensity pulse lasers. He gets a kick out of watching the cells shift in real-time. “We can actually see the thing glowing in the dark,” he said. “It produces beautiful, vivid colors.”

The heart never gets a chance to rest, it’s beating 70 beats per minute, every minute.
— Seth Robia, PhD

The work continues

Robia is an exercise evangelist. While it’s important to maintain a balanced diet and reduce stress, regular cardio is by far the most effective natural antidote to heart failure. Even minor adjustments in a person’s physical routine—taking the stairs, walking on a treadmill periodically—can have outsized effects. “All through our history as a human race, we’ve had a much more active lifestyle than we do now, with our leisure time and sedentary jobs,” Robia said. “We have to compensate for that deliberately. It’s hard to do enough exercise to treat the human body the way the human body was designed to deal with life.”

As long as heart failure remains prevalent and dangerous, though, scientists at Loyola will continue to investigate what happens when our finely-tuned engines fail to turn over. “In a perfect world,” Kirk said, “a person shouldn’t have to think about her heart at all.”

Inside the three-year-old CTRE headquarters, Loyola has amassed a cluster of decorated scientists interested in cardiac function and disease. Compared to cramped older labs, the building’s open floor plan allows for unplanned scientific interactions, and down the block, Loyola Medicine’s cardiology department opens the door for further clinical collaboration. “We work together to come up with new ideas, things to test, new ways to help patients,” Robia said. “Then the physicians can take the discoveries we make here in the lab and hopefully apply those to treatments.”

At the same time, progress on heart failure remains irritatingly slow, at Loyola and across the country. “Almost everybody knows somebody who has heart problems,” Kirk said. “A lot of people work on this issue. And we’ve sucked at actually curing heart failure! It’s really complex.”

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