Nitrite may have a place in rescuing heart muscle cells after a heart attack, according to research by medical student Felix Gonzalez and his NIH mentors.

After fleeing Cuba, this medical student tested a new treatment for heart attack.

Cuban-born Felix Gonzalez decided early that he wanted to be a doctor. At age 16, he entered medical school. Three weeks into his studies, however, soldiers burst into his classroom, lined up all the young men, and took them to be enlisted in the Army.

“I had been training how to save lives,” says Gonzalez, “and now they were training me to take lives.”

Fast-forward 12 years. Gonzalez is close to earning his U.S. medical degree. During two years as an HHMI-NIH Research Scholar, the tenacity that helped him recover his dream led to findings that may yield a new therapy for heart attack patients.

With lead investigators Mark T. Gladwin and Andrew E. Arai at the National Heart, Lung, and Blood Institute, NIH, Gonzalez showed that a ubiquitous chemical, nitrite, can prevent cellular damage in dogs after a heart attack, and the treatment has moved into human studies.

During a heart attack, when blood supply to the heart muscle is blocked, the lack of oxygen kills some heart muscle cells through necrosis, a process in which the cells' internal parts break apart. Treatments such as drugs, stents, and balloons aim to open blocked arteries to improve blood flow after a heart attack. The return of oxygenated blood (reperfusion), however, can cause a second round of damage. Remaining cells become stressed and begin the process of apoptosis (cell suicide) instead. Apoptosis may be triggered by reactive oxygen species—unstable molecules containing oxygen—which deliver a final blow.

This study confirmed that nitrite improved the percent of heart muscle that was salvaged by restoring blood supply to the heart. Nitrite also dilates veins and arteries, which helps restore blood flow to cells at the center of the affected area. Additionally, nitrite seems to protect the cells from reactive oxygen species, reducing apoptosis.

The researchers used magnetic resonance imaging to observe dog hearts before, during, and after a simulated heart attack in which blood flow in the coronary arteries was blocked and then restored. About 70 percent of heart cells deprived of blood died in the untreated control animals. In dogs treated with nitrite for an hour before reperfusion, however, fewer than a quarter of the heart cells died. The results of the study were published June 10, 2008, in the journal Circulation.

Photo: Christopher Jones

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