An animal study published in the February 2008 issue of Anesthesiology has found that inhibiting specific enzymes during mechanical ventilation of the lungs reduces the amount of potential damage to the lungs and even helps to protect the kidneys.

According to Arthur S. Slutsky, M.D., a critical care specialist at St. Michael's Hospital and the University of Toronto, the mechanical ventilators that are used to help certain patients with their breathing can sometimes be harmful to them.

"Very sick patients sometimes need prolonged mechanical ventilation, and besides the originating disease that is causing problems with the lungs, the ventilator can add to that injury," he said. "Prolonged mechanical ventilation alters the physiology and chemistry of the lungs."

In Dr. Slutsky's study, rats were subjected to mechanical ventilation while receiving a potent drug called PJ-34. As expected, the animals receiving ventilation experienced an increase in activity of an enzyme referred to as PARP. The primary role of PARP is to sense DNA damage, repair that DNA when it is damaged, and maintain stability in the body's cells.

However, when severe DNA injury occurs because of oxidative stress, such as during mechanical ventilation, excessive PARP production can actually disrupt cellular stability and cause cell dysfunction and death. In a nutshell, excessive PARP during mechanical ventilation can cause lung damage and contribute to poor lung function, said Dr. Slutsky.

In the last decade, doctors and researchers have made significant progress in the treatment of patients with severe lung diseases. A study published in the year 2000 by a group of NIH-sponsored investigators demonstrated that a gentler ventilating procedure decreased mortality by 22 percent and led to changes in the way acute lung disease and injury are treated today.

Dr. Slutsky's study is the first, though, to demonstrate that targeting PARP using pharmacological therapy with PJ-34 might be a protective measure during mechanical ventilation.

"After treatment with PJ-34, we found that PARP activity was blocked and ventilator-induced damage in the lungs was decreased," he said. "We also found that the same treatment protected the kidneys from cellular death."

The clinical effects of ventilator-induced injury may extend beyond the lungs, Dr. Slutsky said. Lung injury caused by mechanical ventilation can result in the release of substances in the body called inflammatory mediators that lead to what is called "biotrauma," which has been suggested to cause kidney and other organ dysfunctions.

"Biotrauma may be the missing link between treatment for acute respiratory problems and kidney dysfunction," Dr. Slutsky said. "Therapy with PJ-34 for ventilator-induced lung injury is based on regulating biotrauma using anti-inflammatory interventions to help limit the consequences of ventilator-associated organ injury."

Although Dr. Slutsky's study offers scientists new and exciting insights for further research into a problem that continues to challenge physicians and patients, he noted that more study is needed before use of PJ-34 can be translated to humans in any significant way.

Founded in 1905, the American Society of Anesthesiologists is an educational, research and scientific association with 43,000 members organized to raise and maintain the standards of the medical practice of anesthesiology and improve the care of the patient.

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