Selenide protects heart muscle in the wake of cardiac arrest

Damage to heart muscle from insufficient blood supply during cardiac arrest and reperfusion injury after blood flow is restored can be reduced by nearly 90 percent if selenide, a form of the essential nutrient selenium, is administered intravenously in the wake of the attack, according to a new preclinical study by researchers at Fred Hutchinson Cancer Research Center. Mark Roth, Ph.D., and colleagues in the Fred Hutch Basic Sciences Division have published their findings online ahead of the July print edition of Critical Care Medicine.

"We found that administration of selenide after the heart has been deprived of blood flow and before blood flow is restored significantly protects the heart tissue in a mouse model of acute myocardial infarction and reperfusion injury," Roth said.

Ischemia, or insufficient blood supply, as occurs during a heart attack or stroke, causes tissues to become starved of oxygen. In the highly oxygenated tissues of the heart and brain, ischemia can cause irreversible damage in as little as three to four minutes at normal body temperature.

Reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen. The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and oxidative damage through the induction of oxidative stress rather than restoration of normal function.

Using two different mouse models of ischemia reperfusion injury, Roth and colleagues found that selenium is specifically taken up by injured tissues following temporary loss of blood flow while blood selenium levels simultaneously decrease.

"These results suggest there is a natural mechanism that targets selenide to recently reperfused tissue and protects it from injury," Roth said.

To assess the role of the body's naturally occurring selenide in tissue repair, the researchers conducted a series of experiments in a mouse model.

First, they induced ischemia by temporarily blocking the left anterior descending coronary artery for 60 minutes. Blood flow was then restored and selenium levels in the blood and heart were measured two hours later. "We observed that the greater the injury, the greater the loss of selenium in the blood and the greater amount of selenium was found in the heart," Roth said.

To determine whether the buildup of selenium in injured tissues could happen elsewhere in the body and not just in the heart, Roth and colleagues repeated the experiment in a mouse model in which blood flow was temporarily stopped in one of two hind limbs. In the first five minutes after blood flow was restored, they observed a five-fold increase in the amount of selenide in the injured limb as compared to the untreated limb.

"These results, along with prior understanding of selenium biology, show that endogenous, or naturally occurring, selenium is rapidly mobilized from the blood to help protect injured tissue after blood flow is restored," Roth said. "This led us to wonder whether supplementing the body's naturally occurring selenide with an infusion of selenide might further protect tissues after a heart attack once blood flow is restored."