Improving Gastrointestinal Tract Healing in Horses after Colic

Cutting-edge research conducted on microscopic tunnels in horses' intestinal walls has revealed that these channels play a key role in helping intestines heal after life-threatening colic episodes.

These tunnels, called chloride channel 2 (ClC-2), are for chloride ions located in the lining of the gastrointestinal tract near tight junctions. These tight junctions form when the outer membranes of two cells, like those of the lining of the intestine, "fuse" together to form an almost impermeable barrier. Together with the chloride channels, tight junctions play an important role in regulating the permeability (leakiness) of the intestinal wall.

Anthony Blikslager, DVM, PhD, professor of equine surgery and gastroenterology in North Carolina State University's Department of Clinical Sciences, and colleagues discovered ClC-2 in 2004 and have tried to establish how they work and, more importantly, how to make them work better when the intestines are injured.

"The subject of tight junctions is a hot area of research," said Blikslager. "The thinking is that injured sections of the gastrointestinal tract--such as the injury that occurs after the intestine twists--heal very much like a skin wound would, except that the tight junctions of the intestine have to be reconstructed to prevent leakiness."

With gastrointestinal diseases such as colic, neither ClC-2 nor the tight junctions are able to stop the absorption of solutes, bacteria/microorganisms, and endotoxins (highly toxic molecules derived from bacteria) into the horses' bloodstream.

"We have shown that after the blood supply has been cut off to the intestines, like when the intestines twist, leaky tight junctions readily allow endotoxins to get across the lining of the intestinal tract," he continued. "Probably most of the endotoxemia we deal with in the bowel after surgery or during a severe medical colic case is absorbed by horses via the tight junctions."

Blikslager's ultimate goal in this research is to devise a targeted way of activating ClC-2 to potentially speed up the intestinal recovery process, ergo minimizing the absorption of endotoxins.

One way to hasten the recovery of injured intestine is via the use of compounds called prostones, which activate the chloride channels.

"Studies in pigs showed that prostones dramatically sped up the recovery process," explained Blikslager. "In horses the hope would be that prostones could be used to speed up the recovery process."

Blikslager and his colleagues patented this idea in 2007 and an oral prostone drug (Lubiprostone) is on the market, which he says is designed to be given during the first 48 hours after colic surgery.

Blikslager and his team currently are conducting research in mice and cell cultures to better understand how ClC-2 help repair the tight junctions.

Disclaimer: Seek the advice of a qualified veterinarian before proceeding with any diagnosis, treatment, or therapy.

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