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After Shock –
Team Looks at Common Cause of Death

$8 million grant supports Trauma Research Center's study of GI tract's role in multiple organ failure

 

No intervention that's regularly performed in the Shock Trauma Intensive Care Unit (ICU) is immune from the scrutiny of Frederick A. Moore, M.D.

Why? "We look hard at what is routinely done in the Shock Trauma ICU and ask, 'How does this treatment affect the gut function?' We are finding that when a person is critically ill, the gastrointestinal (GI) tract doesn't work. If we can make the gut work better, then we can prevent a lot of infection," said Moore, director of the Trauma Research Center for the Pathogenesis of Multiple Organ Failure at The University of Texas Medical School at Houston.

The Trauma Research Center's major focus is to clarify the role the gut plays in disease when multiple organs begin to fail as a result of trauma. The National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH) recently renewed funding for a Trauma Center Grant with a five-year $8 million commitment to continue research on multiple organ failure, the most common cause of late Shock Trauma ICU death following major traumatic injury.

A multidisciplinary research unit, the center involves investigative efforts of basic and clinical scientists in the departments of Surgery, Internal Medicine, and Integrative Biology and Pharmacology.

Moore, who is the James H. "Red" Duke Jr., M.D., Professor in Surgery, said, "In the lab, we look into why the gastrointestinal system malfunctions following shock and sepsis, or infection. Our researchers are always examining the critical role gut dysfunction plays in multiple organ failure. We do know the gut becomes progressively dysfunctional, and if we can not feed via the gut, then it becomes the reservoir for bacteria and toxins that cause late sepsis."

The center is widely known for its research in gastrointestinal motility and expertise in the stomach.

"We know that stress can cause significant gastric bleeding and, in the past, we focused on how to prevent this bleeding," Moore said. "Today, stress gastritis bleeding is no longer a common problem. Now, with more knowledge about the molecular events that regulate inflammation of the stomach, we are studying how to limit adverse inflammation to improve gastric function. This will reduce the risk of aspiration pneumonia and improve our ability to feed patients."

He outlined four main areas of research:

• Resuscitation - "Post-traumatic shock and resuscitation activate cell-specific molecular events that can contribute to gut injury and dysfunction. We now are developing computerized decision support in the Shock Trauma ICU to assure more consistent resuscitative efforts. We also are studying the role of artificial hemoglobin solutions and hypertonic saline in ensuring optimal gut resuscitation."
• Sedatives and analgesics - "When people are in a lot of pain, they are often given high doses of morphine. But what about morphine's effects on the gut?"
• Enteral nutrition - "The popular belief is that enteral nutrition (feeding via a tube inserted into the gut) doesn't work. But it does. We are exploring ways in which infection might be prevented via early enteral feeding, and we want to know how that can be done and refined."
• Prevention of inflammation - "We are expanding the scope of early enteral nutrition by exploring what we can administer into the lumen (cavity) of the gut during resuscitation to prevent shockinduced inflammation and injury. Examples include novel phospholipid (special types of fats) solutions and glutamine, a semi-essential amino acid and a preferred nutrient of the gut mucosa. We want to feed the patient earlier than we do now, and this research will help us find out how."

The center also offers the Trauma Research Fellowship Program, funded by a NIGMS training grant. This two-year program is aimed primarily at surgeons who are interested in pursuing academic careers in trauma. The participants perform independent laboratory investigation in collaboration with scientist-mentors to enhance basic understanding of trauma-related disease.

NIGMS emphasizes "translational science," Moore said. "Doing research is important. Taking that research from the lab into the Shock Trauma ICU is essential.

"The nice thing about the Trauma Research Center is that young investigators can come in as junior faculty and take advantage of its resources to generate novel ideas and the preliminary data for NIH young investigator grants," he said. "In the academic setting, they are expected to be clinically active, as well as involved in research in their fields. Through these grants, those young scientists are under less pressure to generate their own income."

Three Department of Surgery faculty members who have received these NIH young investigator grants for work in the Trauma Research Center are: Charles Cox Jr., M.D., associate professor and director of the Pediatric Trauma Program at Hermann Children's Hospital; Rosemary Kozar, M.D., Ph.D., associate professor; and Emily Robinson, M.D., assistant professor. Kozar also has a faculty appointment at the UT Graduate School of Biomedical Sciences at Houston (GSBS).

The Trauma Research Center was founded in 1988 through the collaborative efforts of Frank Moody, M.D., professor and former chairman of the Department of Surgery, and Norman Weisbrodt, Ph.D., professor of integrative biology and pharmacology and of surgery, who are still active participants. Weisbrodt also has a GSBS faculty appointment.

Before the most recent $8 million grant, NIGMS center funding totaled $11.4 million, plus training grants.

While Trauma Research Center investigators are gratified to garner large federal grants, Moore said it is frustrating that of the Big Three diseases - cancer, heart disease and trauma - trauma research gets "precious little philanthropy. In a city of four million people, we have only two Level I trauma centers - Memorial Hermann and Ben Taub. Both are very busy and nationally recognized as centers of excellence. If either were to close, people throughout the region would suffer tremendously."

By Gay Elliott McFarland