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Science on ICE. Searching for new, safer ways to approach cryotherapy

R. Matt Brothers isn’t an M.D., but he’s tweaking a medical procedure that could save life and limb.

Brothers, an assistant professor in the College of Education’s Department of Kinesiology and Health Education, along with Kenneth Diller, professor of biomedical engineering at UT’s Cockrell School of Engineering, has received a four-year grant to explore how a procedure called cryotherapy can be used to treat patients without causing them injuries or leading to amputation.

Cryotherapy is the treatment of a physical ailment through the use of cold temperatures, and it can be as basic as having a football player dunk his leg in an ice bath after a game or the procedure can be employed in complex orthopedic surgeries.

While the number of people who have benefited from cryotherpay is immeasurable, the procedure has significant downsides.

“Currently, there are about 1,500 to 2,000 incidences of cryotherapy induced injury a year in the U.S. alone,” said Brothers, who specializes in cardiovascular physiology. “On the surface you might say, well, what’s the significance? It may seem like a trivial number, but you break that down and you have five, six, seven injuries a day.”

Brothers lab group shot

Pictured (left to right): Janee Terwoord, Kevin Christmas, Dr. R. Matt Brothers, Chansol Hurr, Jordan Patik

These injuries range from tissue necrosis (the death of cells due to lack of blood flow) to neuropathy (damage to the peripheral nervous system) and, in extreme cases, amputation.

Most simple applications of cryotherapy carry little or no danger, but when someone has sustained cryotherapy treatment, such as with knee surgery, there is a distinct risk of harm, according to Brothers.

The reason? In an extended cryotherapy treatment, during which a patient may have a limb submerged in icy water for several hours, blood flow in the treatment area reduces by 90 percent. When the limb is removed from the ice bath skin temperature returns to normal fairly quickly, but blood flow in the affected area remains at 10 percent of its baseline value for up to two or three hours post-treatment.

According to Brothers, this restriction of blood and oxygen supply to tissues – called “ischemia” – can have disastrous consequences.

“Currently, there are about 1,500 to 2,000 incidences of cryotherapy induced injury a year in this country alone.” – R. Matt Brothers, a cardiovascular physiologist specialist

“It’s this state of pronounced and sustained ischemia that is likely causing many of the injuries,” said Brothers. “You’re not watching out for the metabolites that are being produced, not providing new blood, and not providing oxygen. All of this creates an internal environment that makes people more susceptible to injuries.”

Thanks to the National Institutes of Health (NIH) grant, Brothers and Diller have teamed up as co-principal investigators in a new study that may solve that problem.

“Ken’s engineering background and expertise in device design nicely compliments my background in integrative physiology and vascular control, and those two areas of expertise are what this research project demands,” said Brothers.

According to Brothers, the research has three main aims. The first is to identify the core issues – find out how much blood flow decreases and if there is a temperature response to the water that’s applied, for example.

The second aim, which is to mechanistically identify the main source of the blood constriction, is more difficult. Using a delicate process that involves small gauge hollow needles, sterile membranes, and a laser Doppler probe, various drugs that impact blood pressure and heart rate are infused just below the surface of the skin.

A host of antioxidants will be tested to block the response of sympathetic nerves that are most likely causing the stricture. “The beauty of this protocol is that whatever we infuse stays local. There’s really no harm, from a risk standpoint, to the subject because the effect washes out very rapidly,” said Brothers.

The final goal of the study is to design a new cryotherapy device that can overcome the negative complications of the procedure.

“We don’t want to completely inhibit the vaso constriction or the ischemic response,” said Brothers. “There are very real clinical benefits from those in terms of reducing pain and swelling, so there is a need for it. We’re just trying to identify how we can prevent it from being so pronounced for so long.”

Device design could take a variety of directions, but for now Brothers envisions a cryotherapy apparatus that will stimulate enough blood flow to clean out old metabolites and reintroduce fresh blood and oxygen.

“We’re tinkering with different ways to inflate the cuff ever so briefly,” said Brothers. “This will cause pressure to build up that squeezes the blood vessels, washes out what was sitting in there all this time, and re-infuses life.”

Brothers and Diller are just beginning the research project, so hard data and final results are still a long way off.

“With this kind of work, very rarely do you answer a question and consider the investigation definitely done,” said Brothers. “You find information that has an effect and then you build on that and build on the next thing. I see who-knows-how-many subprojects resulting from this grant. Even considering all of the uncertainties, I’m very optimistic that the outcome will deliver widespread benefits.”

-Video by Christina S. Murrey