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Shock Block: Preventing Deaths in the ICU

We're all going to die, but some ways are more preferable than others. For instance, a woman in Washington State is suspected of smothering her boyfriend to death with her breasts. Me? I'd prefer that an anvil fall on my head (a la Wile E. Coyote) after my 100th birthday: quick and (probably) painless.

But, most of us won't be that lucky. In fact, each year in the U.S., hundreds of thousands of people die in intensive care units from circulatory shock, a condition in which insufficient oxygen and nutrients are delivered to the body's tissues. Left unchecked, shock can lead to organ dysfunction, which is often followed by that ultimately irreversible symptom: Death.

Intestinesbeforeaftertreatment.jpgShock has multiple causes. Two common types include hemorrhagic shock, which occurs following traumatic blood loss, and septic shock, which occurs following systemic bacterial infection. Both lead to hypovolemia (low blood volume) and hypotension (low blood pressure), which cause organ dysfunction.

Additionally, the intestines play a major role in shock, and it is thought that proteases (digestive enzymes) secreted by the pancreas break through the intestine's mucosal barrier, digesting the intestinal wall. Even worse, the enzymes can enter systemic circulation and damage other organs, greatly exacerbating the problem.

Researchers from UC-San Diego wanted to determine if blocking these enzymes could help rescue rats suffering from shock induced by blood loss, peritonitis (abdominal inflammation due to infection) or endotoxin (a bacterial membrane molecule which causes septic shock). They found that injecting enzyme inhibitors directly into the small intestine greatly increased survival and decreased organ damage. (See figure. Top panel: Normal intestines; middle panel: shock; bottom panel: shock + enzyme inhibitors.) Damage to the lungs and heart was also reduced when the rats were treated with enzyme inhibitors.

Given the success observed in the rat model, the authors hope to see the same in human patients.

Source: F. A. DeLano, D. B. Hoyt, G. W. Schmid-Schönbein. "Pancreatic Digestive Enzyme Blockade in the Intestine Increases Survival After Experimental Shock." Sci Transl Med 5, 169ra11 (2013).

Source and image source: "Blocking Digestive Enzymes May Reverse Shock, Stop Multiorgan Failure." UCSD press release. January 23, 2013.

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