News Release

Medicine implants drastically reduce stroke complications

American Stroke Association journal report:

Peer-Reviewed Publication

American Heart Association

DALLAS, April 5 – Implanting tiny rods containing a calcium-channel blocker in brain vessels prevented vasospasm, a complication that can occur after surgical repair of a brain hemorrhage, according to a report in today’s Stroke: Journal of the American Heart Association.

A subarachnoid hemorrhage (SAH) is a type of stroke. It occurs when an aneurysm, a blood-filled pouch, balloons out from a weak spot in the artery wall and bursts. Then the vessel bleeds into the space that covers the surface of the brain with spinal fluid. Surgery is required to repair the vessel. A patch or artificial piece of blood vessel is sewn over the rupture.

A major complication of SAH is vasospasm, a prolonged contraction of the artery walls. “Vasospasm is a major cause of death and disability because it can reduce blood flow enough to kill brain tissue,” says Hidetoshi Kasuya, M.D., lead author of the study and a senior lecturer in the department of neurosurgery at Tokyo Women’s Medical University. “In this study, vasospasm was completely prevented by inserting the pellets of the medication next to the arteries where vasospasm was most likely to occur.” The new drug delivery system, implanted during surgery, uses a calcium-channel blocker, which dilates the blood vessel.

The 20 patients in this study had SAH. “Aneurysmal SAH accounts for approximately 6 percent to 8 percent of all strokes and affects more than 28,000 individuals in North America each year,” he says.

In the current study, two to 10 pellets of nicardipine – a common calcium-channel blocker used to treat high blood pressure – were implanted during brain surgery. They were placed parallel to the arteries and adjacent to thick clots identified during the surgery. The drug has a localized effect in the brain, so the patients’ own blood vessels in distant parts of the brain were used as controls in the current study, he explains.

In the first three days, about 7 percent of the nicardipine was released with 46 percent after the next three days. The amount of nicardipine released within the first nine days was 62 percent of the total amount.

The risk of vasospasm is rarely significant before the fourth day following the initial hemorrhage. It reaches a peak around the eighth day, when about 70 percent of patients have some narrowing in one or more arteries, Kasuya says. The risk of vasospasms decreases substantially two weeks after a SAH.

The subjects’ vessels were examined using angiography at seven and 12 days after surgery. All vessels adjacent to the medication pellets remained free of vasospasm. Eight of the 20 patients experienced vasospasm in arteries remote from the medication site. The contraction was mild in six patients, moderate in one and severe enough to cause disability in one patient. This is far below the rates seen in untreated SAH patients.

No side effects were reported, possibly because such focused, time-released treatment allows doctors to drastically reduce the dose, says Kasuya.

“This drug system is the most promising approach for preventing vasospasm,” he says. The next step would be to develop a treatment based on this technology.

Even when aneurysms are found early and treated with surgery the outlook is cloudy because of vasospasm. The reduced blood flow from a vasospasm can cause an ischemic stroke, he adds.

Physicians don’t know what causes vasospasm, but it seems related to blood clots in the large vessels that run between the two sides of the brain. Current treatments to reduce or prevent vasospasm are either difficult to administer, prone to complications or both, the researcher explains.

“Our results suggest that nicardipine can prevent vasospasm completely if appropriate concentrations are maintained around the broken vessel using the newly-developed drug delivery system,” says Kasuya. “We show that this system is an effective, simple and safe treatment for preventing vasospasm.”

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Co-authors include Hideaki Onda, M.D.; Mikihiko Takeshita, M.D.; Yoshikazu Okada, M.D.; and Tomokastu Hori, M.D.

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