Bypassing failure with a good workout

The human heart chugs along 24 hours a day, running a relentless lifelong marathon. Modern medicine has extended the race for many people, and coronary artery bypass surgery is one reason why — more than 400,000 people a year undergo some version of the life-prolonging procedure in the U.S. alone.

John Eberth, an assistant professor of cell biology and anatomy in the School of Medicine, is working to ensure that as many of those patients as possible never experience a serious and not uncommon complication — the failure of the bypass itself.

Although complex in practice, a heart bypass procedure is simple in theory. When an artery that keeps heart muscle supplied with oxygen-rich blood starts to clog, a surgeon will harvest a healthy blood vessel from elsewhere in the body and graft it into place to provide an alternate path for blood to flow.

Those newly grafted vessels, however, can become occluded and fail. Eberth is using a biomechanical approach to understand why — and develop ways to prevent failure.

“Historically, about 15 percent of grafts fail in the first year,” Eberth says. “But more recently surgeons started to harvest vessels from a different source, with better success.”

Originally, the primary source for coronary artery grafts was the saphenous vein, which comes from the leg. For many years, it was the blood vessel of choice for heart bypass surgery.

Over the past two decades, a vessel taken from the chest, the internal thoracic artery, has largely supplanted the saphenous vein as the blood vessel of choice for a bypass. Better long-term results is the major reason for the change. The 15 percent failure rate with the leg’s saphenous vein contrasts with about a five percent rate with the artery from the chest.

For an engineer with Eberth’s background — doctoral degree in biomedical engineering and bachelor’s and master’s degrees in mechanical engineering — the difference in results immediately begs a number of questions. To Eberth, the entire heart bypass enterprise seems to work a lot better than it might be expected to from a mechanical point of view.

“I was asking the question, ‘How do these vessels work, either of them?’” Eberth says. “How do saphenous veins even work 85 percent of the time? Because a vein is not an artery — it’s from a completely different environment.”

Arteries deliver blood from the heart to the extremities, whereas veins return blood to the heart. By virtue of being further downstream from the pump, veins operate under more steady-flow, lower pressure conditions than arteries.

Trying to get a vein to work in an arterial environment — particularly in one as demanding as that experienced by a coronary artery — would likely fail a lot more often if the grafted vessel remained unchanged. But, fortunately for bypass patients, blood vessels have an inherent adaptability.

The vasculature is able to ‘remodel’ its structure in response to new stresses. Generalized high blood pressure, for example, can bring about biomechanical changes in blood vessels that help ameliorate the overall effect. A vein placed in an arterial environment doesn’t stay the same in a cellular and biomechanical sense — it adapts.

Eberth and colleague Tarek Shazly, an assistant professor in the Department of Mechanical Engineering, have begun looking carefully at the biomechanical makeup of grafted veins and arteries before and after placement. They’ve built and patented what they call the Descartes Perfusion BioreactorTM, a device that can gradually change the pulsatile pressure and flow on a harvested vessel over the course of weeks to achieve mechanical objectives.

With it, they can assess how microstructure both correlates with mechanical conditions and changes when a vessel encounters new environmental conditions. Eberth has established that a saphenous vein and a thoracic artery have distinct baseline differences in the quantity and placement of fibrous, muscular, and elastic tissue, and the Descartes Perfusion Bioeactor can be used to guide the remodeling processes.

Their device is more than just a research tool: The ultimate goal is to develop a way for physicians to condition blood vessels so that they’re ready to be grafted into entirely new environments.

“Sometimes surgeons can’t use their first choice for a graft,” Eberth says. “Maybe the thoracic artery is compromised or it’s a quadruple bypass and you need to use more than one vessel. We want to develop a system where you can take the first, second or third option and condition it for the new environment.”

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