Alberta Innovates- Health Solutions

Sepsis, the spread of infection through the body, is one of the biggest killers in North American intensive care units. Despite treatment, 40-60% of sepsis patients die. New technologies and drugs offer hope of improving survival rates, but complicating factors include hospital-acquired infections and rising resistance to traditional antibiotics.

University of Alberta Heritage researcher, Dr. Richard Schulz, investigates the basic biochemical functioning of cells, in particular heart cells, in cases of sepsis. By developing therapies to alter the responses to infection at the cellular level, it might be possible to alter the body's reaction to the biochemical processes of infection.

During an infection, the body mounts defense forces such as white blood cells in the immune system. “White blood cells, in response to immune activation, start making huge amount of NO (this nitric oxide also regulates blood-vessel and heart function) which is used to kill off the pathogen. Heart cells, too, appear to have this ability to produce massive amounts of NO. But one of the properties of NO is that, in excessive amounts, it damages tissue. This is the lesser of two evils. On one hand, without NO, a heart-cell-attacking virus would completely destroy the heart. On the other, with the extra NO production, the heart is trying to fight back, even if it gets damaged by the very weapon it is using,” says Dr. Schulz.

By blocking NO production during sepsis, experiments showed dangerously low blood pressure was restored to normal within minutes. “But sepsis isn't just a problem of low blood pressure. It's a situation where the heart's function as a pump is depressed.” Dr. Schulz introduced sepsis-like toxins into the heart and discovered that the form of NO produced, contributed to depressing heart function.

Dr. Schulz applied his knowledge to an investigation with Dr. Ruth Collins-Nakai into the causes of heart tissue injury after bypass surgery. Reperfusion, the term for diverting warm blood back to the heart after it's stopped during surgery, can cause temporary or permanent injury to heart tissue. Excess NO production was the culprit along with other free-radical compounds like superoxide.

Superoxide is not toxic by itself but when combined with NO results in a substance called peroxynitrite. Peroxynitrite decomposes within the body to form destructive oxidant molecules which target the membranes, proteins, and genetic machinery of cells.

Dr. Schulz can reduce reperfusion injury by:

• stopping excess production of NO with drugs
• blocking superoxide production

He believes peroxynitrite also depresses heart function during septic shock. Dr. Schulz must now find out how peroxynitrite works in hope of developing therapies to target proteins affected by it.

For more information on heart health, check the