New Study Could Lead To Better Treatment Of Septic Shock

A healthy immune system is the first line of defense against bacterial infections in the bloodstream. But in about 200,000 of those cases per year, the immune system runs out of control, turning against the body in an attack known as septic shock. Those afflicted initially may experience flu-like symptoms followed by a drop in blood pressure, which can contribute to tissue and organ damage. Ohio University scientists studying the mechanisms that cause blood pressure to plummet in these patients have found a possible culprit: a dangerous interaction of nitric oxide – a natural compound involved in regulating blood circulation – and free radicals, harmful chemical byproducts created during an immune system response. Both are produced in abundance during septic shock.

Studies suggest that the potent combination produces a substance called peroxynitrite, which causes a normal immune response to go haywire, damaging blood vessels and triggering blood vessel leakage. This lowers blood pressure in patients with septic shock, said Richard Klabunde, lead author of the study and associate professor of biomedical sciences in the College of Osteopathic Medicine, who recently presented the work at the annual meeting of the Microcirculatory Society in Orlando, Fla.

In a normal immune response, cells release platelet activating factor (PAF). The chemical prompts inflamation, isolating invading bacteria so they can be destroyed. But scientists have observed that in septic shock patients, PAF plays a different role – it causes blood vessel leakage.

The new study suggests that a mixture of high levels of nitric oxide and free radicals must be present for PAF to wreak such damage on the circulatory system. Researchers used two drugs to test what impact nitric oxide or free radicals have on PAF-induced vessel leakage. One drug inhibits the formation of nitric oxide; the other scavenges free radicals. The researchers found that by blocking the production of either the nitric oxide or free radicals, they could reduce blood vessel leakage.

"If we block either one, we have this effect," Klabunde said. "This means that both are important and suggests that they are both interacting to produce a substance that causes the vascular leakage."

The drugs used in the animal study are not approved for human use, Klabunde said, so a new therapy would need to be developed for patients with septic shock.

To combat the condition, hospitals currently administer drugs and fluids to patients to maintain blood pressure and use antibiotics to fight the infection. But antibiotics can backfire, Klabunde noted. As the bacteria that cause septic shock die, they may release a toxin into the bloodstream, making the situation worse.

No single drug exists to combat septic shock, and it's not clear why some patients survive it while others don't, he added. In related research, Klabunde is examining how high doses of antioxidants – which scavenge free radicals in healthy bodies – may protect the heart during septic shock.

Co-author of the study is Denise Anderson, a research technician in the university's College of Osteopathic Medicine. The research is funded by the Ohio Valley Affiliate of the American Heart Association.