Portland, Ore.

Improved design of recently patented device reflects vision of Charles Dotter

In the mid-1990s, when medical device manufacturer Cook Group Inc. was shown a square stent and a square stent-based occluder developed at Oregon Health & Science University, the company had an idea.

A Cook engineer asked one of the stent's developers, Dusan Pavcnik, M.D., Ph.D., if he could build a venous valve from the stent and the large-vessel occluder. Only one mantra came to Pavcnik's mind: "Never say never."

His determination paid off. The device, a bioprosthetic bicuspid venous valve, which began as a square stent conceived in 1992 by scientists at the Dotter Interventional Institute, OHSU School of Medicine, is expected to be patented in the near future. Successfully tested in more than a dozen sheep and already licensed to Bloomington, Ind.-based Cook, the scaffold-like apparatus could be in clinical trials this year.

"It's definitely satisfaction," says Pavcnik, research professor at the Dotter Institute. "It proves that dreams can become reality, that what you planned can come true, that the hypothesis actually works."

The artificial bioprosthetic venous valve is a sturdier, second-generation version of a device invented several years ago at the Dotter Institute in collaboration with Cook. The valve can be placed in the deep veins of the legs percutaneously - with a catheter thread through a small puncture in the skin - without surgery.

The old valve consisted of a thin, flexible piece of FDA-approved biomaterial called small intestinal submucosa, a connective tissue-based product derived from the small intestines of pigs. The material was sutured to a square stent made from stainless steel wire that served as a frame, and a slit was cut diagonally in the membrane.

When the stent was folded at opposite corners, the membrane became a one-way valve. During testing in sheep, the valve functioned well in 88 percent of cases, but occasional tilting of the valve was a problem.

The new valve improved at Cook Inc. solves the tilting issue. It now has two overlapping stents made from nitinol, a nickel and titanium alloy, providing four extra points where the device contacts the inner wall of the vessel.

The new double-stent design "will always center perfectly. It cannot tilt," Pavcnik says. "We had no tilting at placement into the jugular veins in sheep, and valves exhibited good function in more than 90 percent of cases."

The biomaterial is a connective tissue that becomes the framework for cells after its placement into a vein. It becomes "remodeled" by host tissue cells, a process that takes only three months.

"Cells go in and take it over," Pavcnik says. The biomaterial also can be stored for long periods and simply rehydrated before use.

Pavcnik says advanced chronic venous disease can be crippling. Deep venous insufficiency is a clinical condition characterized by hypertension in the lower extremity due to incompetent or destroyed valves. Symptoms range from tiny, spider-like veins and large, blue, rope-like varicose veins to skin discoloration, ulcers and swollen, painful legs.

Patients with "incompetent" or absent venous valves and deep venous insufficiency syndrome can benefit from the artificial valve.

"We believe replacing the incompetent valves will improve the condition," Pavcnik says.

Frederick S. Keller, M.D., professor and chairman of diagnostic radiology in the OHSU School of Medicine, and director of the Dotter Institute, says the venous valve's development epitomizes the creativity and drive of Dotter Institute scientists.

"Our research has been directed toward developing new, and improving existing, interventional devices and image-guided surgical procedures, and this venous valve is a revolutionary new device which has the potential to benefit tens of millions of patients," says Keller, also a professor of surgery in the School of Medicine.

The valve also is a good example of the kinds of life-saving devices and techniques Charles Dotter, M.D., envisioned when he pioneered angioplasty at OHSU in 1964.

"He predicted there would be percutaneously placed heart valves and that angioplasty would be extended to every artery in the body, and that image-guided interventional technique would replace the large part of vascular and oncologic medicine," Keller says.

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