Study Shows Pharmacological Therapy May Protect Ventilator Patients

February 15, 2008

A study published in the February issue of Anesthesiology is the first to demonstrate that targeting the enzyme PARP using pharmacological therapy with PJ-34 might be a protective measure during mechanical ventilation.

In the study, rats were subjected to mechanical ventilation while receiving a potent drug called PJ-34. The animals receiving ventilation experienced an increase in activity of PARP, which senses DNA damage, repairs damaged DNA and maintains stability in the body's cells.

When severe DNA injury occurs because of oxidative stress, such as during mechanical ventilation, excessive PARP production can disrupt cellular stability and cause cell dysfunction and death. Excessive PARP during mechanical ventilation can cause lung damage and contribute to poor lung function, said Dr. Arthur Slutsky, a critical care specialist at St. Michael's Hospital and the University of Toronto, and study author.

"After treatment with PJ-34, we found that PARP activity was blocked and ventilator-induced damage in the lungs was decreased," Slutsky 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, Slutsky said. Lung injury caused by mechanical ventilation can result in the release of substances in the body called inflammatory mediators that lead to 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," 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."

Slutsky noted that more research is needed before use of PJ-34 can be translated to humans in any significant way.