Pancreatic enzymes may play role in shock

Among its duties, the pancreas produces digestive enzymes and dumps them into the small intestine. These chemicals are strong enough to break down meats and other foods, yet they don’t normally damage bodily tissues. The inner lining of the intestine forms a barrier that keeps the enzymes in their place.

A normal human white blood cell (left) contrasts in shape with a white blood cell (right) that has been activated as if during shock. In rats, inhibiting pancreatic enzymes keeps the cell in the robust, round shape. Scale bar is about 1 micrometer. University of California, San Diego

Scientists now suggest that when pancreatic enzymes leak out of the intestinal tract, they set off the devastating chain reaction known as shock. Marked by confusion, clammy skin, plummeting blood pressure, a weak heartbeat, and organ failure, shock can be induced by trauma, blood loss, or deep anesthesia. By blocking the effects of pancreatic enzymes, researchers at the University of California, San Diego in La Jolla prevented shock in rats prone to get it—the first solid evidence that points to enzymes as catalysts for this condition.

Biomedical engineer Geert W. Schmid-Schönbein and his colleagues studied rats in which the researchers had shut off the intestinal blood supply for several hours. Five of these rats were otherwise untreated, whereas the scientists injected an enzyme blocker called 6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfate (ANGD) directly into the intestinal cavity of five others.

The trauma of the blood cutoff sent the untreated rats into shock, while the treated rats remained healthy, Schmid-Schönbein and his colleagues report in the Feb. 15 Proceedings of the National Academy of Sciences.

The researchers used ANGD because studies have shown that it interferes with certain enzymes in the protease family, which includes pancreatic enzymes. In Japan, physicians prescribe such protease inhibitors—different from those used to treat AIDS—for pancreas infections. “This is quite an interesting study,” says physiologist Ronald J. Korthuis of Louisiana State University Health Sciences Center in Shreveport. “It will lead, hopefully, to some therapeutic intervention that blocks these enzymes.”

In response to a lack of blood flow, the pancreatic enzymes leak into the walls of the intestine and then gain access to the bloodstream, Korthuis says. However, this does not seem to be sufficient to explain shock.

Schmid-Schönbein suggests the seepage leads to formation of a still-unidentified substance that—once set loose in the bloodstream—activates cells making up the inner lining of blood vessels.

The normal gatekeeper function of these cells then fails, allowing white blood cells—which are also revved up by the activator substance—to leave the bloodstream and get trapped in vital organs, he says. There, they cause inflammation and tissue damage that can lead to organ failure.

In the study, the untreated rats had high concentrations of white blood cells in their lungs and liver. The enzymes themselves are unlikely to activate white blood cells, however. When the researchers exposed tissue from healthy rats to the enzymes, they saw little inflammatory reaction. When plasma from the rats in shock flooded such tissue, however, it became inflamed. Thus, some unknown activator substance appears to circulate in the blood of rats in shock, Schmid-Schönbein and his colleagues conclude.

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