Treating the Deadliest Part of Cardiac Arrest

The idea grew out of ongoing research involving hemoglobin-based oxygen carriers, known as HBOCs, which are designed to transport oxygen throughout the body. Dr. Wollocko and Dr. Shah believe those compounds, combined with antioxidants, may help address what physicians call the metabolic phase of cardiac arrest.

“Cardiac arrest is one of the world's leading causes of death,” Dr. Wollocko said. “There are at least 400,000 cardiac arrests that occur outside the hospital, and the treatment outcome is still not great.”

According to Dr. Wollocko, treatment for cardiac arrest generally falls into three phases. Defibrillation can restore heart rhythm during the earliest phase, while CPR helps restore circulation during the second. The third phase, the metabolic phase, occurs after prolonged oxygen deprivation.

“Perfectly done resuscitation in a perfectly prepared medical facility can increase the oxygen in the tissue by about 30 percent,” Dr. Wollocko said. “For some people that's enough and they survive. Patients that need more oxygen enter the metabolic phase where we really don't have any treatment options, and it's an unmet medical need.”

Working in a laboratory setting, the team uses a bioreactor to recreate conditions similar to cardiac arrest. The system allows researchers to remove oxygen from a hemoglobin solution and measure how effectively different treatments restore oxygen-carrying capacity.

“We want to mimic the circulatory system,” Dr. Wollocko said. “We are creating a situation where there is no oxygen delivered to the tissue and then testing how quickly we can reverse that situation.”

The project has evolved through years of experiments, and the research team tested a range of antioxidants, including vitamin C and N-acetylcysteine, while studying how each affects hemoglobin's ability to carry oxygen.

“We tried vitamin C in five different doses,” Dr. Wollocko said. “Vitamin C is a peculiar thing. At different doses it works as a reducer or an oxidative agent.”

At higher concentrations, Dr. Wollocko explained, vitamin C appeared to promote oxidation rather than prevent it. “People are usually taking vitamin C like candy,” she said. “But at some point, when it's five times more than the daily dose, it works not as an antioxidant, but it causes oxidation of hemoglobin.”

Finding the right treatment combination has proven challenging. Researchers tested several doses of N-acetylcysteine and continue evaluating additional compounds. One area of particular interest is magnesium, which Dr. Shah had been studying for more than two decades.

“We are trying to improve oxygen delivery to hypoxic tissue that is dying in a short time frame,” Dr. Shah said. “The idea is to optimize the effect of the oxygen carrier.”

Unlike donated blood, hemoglobin-based oxygen carriers do not contain red blood cells. Dr. Wollocko said their smaller size may allow them to reach areas where circulation is restricted. “The advantage of hemoglobin-based oxygen carriers is that they are tiny and can go around occlusions and deliver oxygen where blood cells cannot,” she said.

Although the current work focuses on cardiac arrest, Dr. Shah sees broader possibilities if oxygen delivery can be improved. “Any hypoxic tissue,” he said. “Stroke, chronic renal failure, liver disease, sickle cell disease and neurodegenerative diseases.”

Dr. Wollocko estimates that the team will need at least another year of work as they continue refining treatment combinations and analyzing results. “We are hoping this project will result in saving lives,” Dr. Wollocko said.