Common Drug is Re-engineered to Improve Surgery Outcomes

A Northwestern University research team potentially has found a safer way to keep blood vessels healthy during and after surgery.

When patients undergo vascular procedures, they run the risk of experiencing injuries to their blood vessels, leading to cellular overgrowth that can dangerously restrict blood flow. These complications potentially can be prevented by the delivery of nitric oxide.

“Nitric oxide is a very protective molecule for vasculature,” said Guillermo Ameer, professor of biomedical engineering at the McCormick School of Engineering and surgery at the Feinberg School of Medicine. “Normally, all of the cells inside blood vessels constantly secrete this molecule. It inhibits blood clotting, prevents cell overgrowth that contributes to scarring, and keeps the inside of the vessel healthy.”

Now, Ameer and his team have revamped the long-established drug protamine sulfate into a nitric oxide-releasing drug by exposing it to highly pressurized nitric oxide gas.

“Protamine is a natural compound that has been used in surgeries for many decades,” said Robert van Lith, a postdoctoral fellow in Ameer’s lab. “During open-heart procedures, physicians administer a blood-thinning drug called heparin to prevent clot formation. When given too much heparin, patients can develop complications from excessive bleeding. A common antidote is the compound protamine sulfate, which binds to heparin to reverse its effects.”

While other nitric oxide-releasing drugs do exist, most become toxic after the gas is expelled. Nitrosamine, for example, has been known to cause cancer. Ameer’s team was able to convert protamine into a nitric oxide donor without changing its natural structure. Because protamine already naturally occurs in the body, it did not leave behind toxic byproducts.

“After protamine releases the nitric oxide, it reverts back to its natural form and still works as a heparin antidote,” van Lith said. “This is a much safer alternative.”

Supported by the American Heart Association, the research is now available online and will be published in the May 2015 issue of Free Radical Biology and Medicine. Van Lith is first author of the paper.

Ameer’s team also showed that their new drug could inhibit cell overgrowth to keep vessels open. Next, they plan to mix this new drug with a hydrogel that can be applied directly to the outside of an injured blood vessel to provide long-lasting prevention of cell overgrowth that leads to scarring and obstruction of blood flow.

“We showed that the potential negative effects of nitric oxide donors can be prevented by using this new drug,” Ameer said. “This could be a more effective and safer alternative to a common drug that is widely used.”