“This is a useful therapeutic approach and should be easy to translate,” said Jay L. Zweier, senior study author, working at Ohio State University’s Medical Center. In examining isolated hearts, the research team observed that in hearts subjected to a lack of blood flow, or the ischemia that occurs during a heart attack, the ability of the vessels to remain dilated is impaired because production of the nitric oxide molecule that dilates the vessel stops. This stoppage can be traced to depletion during ischemia of a molecule that is a critical cofactor required to activate the enzyme nitric oxide synthase (NOS), which produces the potent vasodilator nitric oxide. This critical cofactor is a molecule called tetrahydrobiopterin, or BH4.

In fact, the loss of BH4 during ischemia not only prevents production of nitric oxide and the dilation it causes, but actually causes the enzyme NOS to completely reverse course and instead produce an oxidant called superoxide that leads to constriction of the vessels. Because depletion of BH4 during ischemia is irreversible, the heart and coronary vessels cannot generate their own repair – which has important consequences for efforts to restore blood flow. So the scientists also developed a way to package the molecule and deliver it directly to the vessels. They discovered that the treatment was effective in partially restoring the process that opens and dilates the vessels with improved coronary flow.

Zweier said that because this approach controls blood vessel function at the cellular level, BH4 infusion could be used not just for acute heart attack treatment, but also to help prevent new blockages of coronary arteries after procedures such as angioplasty or bypass surgery.

MEDICA.de; Source: Ohio State University