International Study Seeks to prevent Heart Bypass Hazards

The heart-lung bypass machine that stills the heart while surgeons bypass clogged arteries or repair a malformed heart can also trigger a potentially deadly inflammatory response.

Medical College of Georgia surgeons are participating in an international study of a drug that may block the most deadly of these responses during coronary bypass surgery.

“Blood is a very complex fluid with many components,” says Dr. Kevin P. Landolfo, chief of the MCG Section of Cardiothoracic Surgery. Like the heart, three to six liters of blood run through the heart-lung bypass machine per minute, which means total blood volume goes through the machine many times in the hours it takes to perform bypass surgery. “It’s a massive physiologic insult, so our body comes alive with an inflammatory response to (blood) circulating through this unit.”

The response helps prevent infection, but it can cause blood clots that lead to serious complications--including lung or kidney injury, a heart attack or stroke--in 7 percent to 10 percent of patients.

MCG is part of a study to determine whether giving the complement blocker pexelizumab intravenously before, during and after bypass surgery blocks the worst aspect of the inflammatory response. “The immune system is still revved up but we block the most dangerous component of it,” says Dr. Landolfo.

 Surgeons have long recognized the ill effects of bypass. They have changed the way they do surgery, even doing cases without bypass when possible, and the machine itself has been improved, says Dr. Landolfo. “We are pretty good at having patients survive, but it’s all the morbidity related to heart surgery. Much of what remains is related to the heart-lung machine.”

The study of 5,000 heart bypass patients in about 40 states and three foreign countries is looking at this drug in at-risk patients, including those who have had a previous stroke or heart attack or have diabetes. Women are also at risk for serious complications, possibly because their smaller size causes their blood to pass through the machine even more times, Dr. Landolfo says, noting treatment protocols already take this risk into consideration.

He’s optimistic all bypass patients may one day benefit from some form of short-term suppression of the protective immune response, but for purposes of the study--sponsored by Alexion Pharmaceuticals Inc. and P&G Pharmaceuticals--it’s easier to show results in high-risk patients.

His colleague, Pediatric Cardiothoracic Surgeon James D. St. Louis, is trying to understand this potentially lethal inflammatory response in children. “Their response can be profoundly different and profoundly more intense than adults. Children die from it,” Dr. St. Louis says. “We have at least one or two children a year where the operation goes fine then the children will have this spiraling set of circumstances where there is nothing you can do. It’s an immune response,” he says of systemic inflammatory response syndrome following bypass.

“Remember, the vast majority of children do fine,” says Dr. St. Louis. But he thinks some children, particularly those with low oxygen levels before surgery, have trouble activating a natural mechanism that could correct some cell damage caused by bypass.

As blood moves through the machine where carbon dioxide is removed and oxygen is added, oxygen-carrying red blood cells literally get beat up. “It’s a lot better than it was 15 or 20 years ago but it still causes hemolysis,” says Dr. St. Louis. Oxygen-carrying, iron-rich hemoglobin is supposed to be carried by red blood cells. But it can escape from bypass-battered cells, generating oxygen-free radicals that destroy tissue. Macrophages, scavenger-like cells that roam the body, have a surface receptor called CD 163 which binds the protein haptoglobin. Haptoglobin in turn binds free-floating hemoglobin so the macrophages can eliminate it. “One of the theories we have is that in some children, CD 163 may be deficient or not up-regulated as much as it should be,” says Dr. St. Louis.

To better understand the action of CD 163 in these children, Dr. St. Louis is measuring levels in newborns before, during and after surgery and looking at the expression of macrophages in heart tissue.

He’s also looking at the complement system activated by bypass which in children can cause leaking of endothelial cells that line blood vessels. “One of the biggest problems after surgery is the kids swell,” Dr. St. Louis says, a result of this leaking that can pull the blood vessel wall lining apart. “We are trying to figure out why at this point,” he says, noting that children already receive steroids beforehand to up-regulate CD 163 and suppress the immune response.

 He believes the ‘why’ may again be an issue of mal-regulation. One of his clinical studies is looking at expression of factors that regulate immunity, such as NFkappaBeta, in hypoxic and non-hypoxic children. He’s also looking at the contributions of NFkappaBeta to cell leakiness that occurs in some children. “We want to figure out what causes leakiness so we can stop it,” says Dr. St. Louis, who says it’s likely a signaling process that goes back to the oxygen-free radicals released by battered red blood cells.

An animal model he developed is enabling even more detailed studies of both problems.

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Alumnus Receives Outstanding Physician Award

Dr. Jack Butterworth Jr., vice president of medical affairs at Bristol Regional Medical Center and a 1964 graduate of the Medical College of Georgia School of Medicine, has received the Tennessee Medical Association’s 2005 Outstanding Physician Award.

The award is presented annually by the TMA House of Delegates to member physicians who   have made a mark on medicine in Tennessee and on their colleagues.

Dr. Butterworth, a retired urologist, was nominated for the award by the Sullivan County Medical Society. He has been a member of Bristol Regional’s medical staff since 1971. As vice president of medical affairs, he helps identify and implement initiatives that enhance the safety of hospital patients and employees. Areas of emphasis include reducing medical errors, standardizing treatment protocols and efficiently managing hospital resources.

In his ongoing efforts to promote health in the community, Dr. Butterworth spearheaded the Bristol Prostate Screening Program and co-founded the TN-VA Prostate Cancer Support Group. After retiring from Bristol Urological Associates in 2004, he participated in a three-week medical mission trip to the Congo where he treated patients and  provided urology education to local physicians. Dr. Butterworth is certified by the American Board of Urology. He is past president of the Bristol Regional medical staff and a past member of the hospital’s board of directors.

He has served as vice president of the TMA and as a member of the TMA’s Board of Trustees. He is a former president of the Sullivan County Medical Society and former chair of Independent Medicine’s Political Action Committee-Tennessee. He has served on the board of the Volunteer Mutual Insurance Company since 1993 and is a founding member of the Tennessee Urological Association.

Dr. Butterworth is an elder at First Presbyterian Church in Bristol and plays trombone in the Bristol Dixieland Jazz Band.

“Dr. Butterworth is a credit to Bristol Regional Medical Center and a credit to our region,” said Bart Hove, president of the hospital. “He is an accomplished leader and a compassionate professional who is respected throughout the Wellmont Health System. I applaud THA for recognizing his many contributions to quality health care.”

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Dr. Feldman Dies at age 79

Dr. Daniel S. Feldman, Professor Emeritus of Neurology, died June 5 at age 79.

Dr. Feldman earned his medical degree from the University of Pennsylvania and completed a residency and fellowship in neurology at Mt. Sinai Hospital in New York City. He served for 20 years as professor of neurology at MCG, including as residency program director.

Dr. Feldman received a Career Investigator Award from the Health Research Council of the City of New York. He held leadership positions in organizations including the Myasthenia Gravis Foundation, the American Academy of Neurology and the National Multiple Sclerosis Society. He was a senior associate examiner of the American Board of Psychiatry and Neurology.

Survivors include his wife, Dr. Elaine Bossak Feldman, three children and three grandchildren.

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In Appreciation

President and Mrs. Daniel W. Rahn hosted a reception at their home June 16 for Dr. David Stern in appreciation for his tenure as dean of the MCG School of Medicine from 2002 until August 2005. Dr. Steve J. Schwab, chair of the Medical College of Georgia Department of Medicine, is serving as interim dean as a search committee seeks a permanent successor. Dr. Stern joined the University of Cincinnati College of Medicine as dean.

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Dr. Prisant Named Chapter President

Dr. L. Michael Prisant, director of the Hypertension and Clinical Pharmacology Unit at the Medical College of Georgia, has been elected to a two-year term as president of the Carolinas and Georgia Regional Chapter of the American Society of Hypertension.

The chapter works to increase awareness among physicians of hypertension, related diseases  and treatments.

He is a certified American Society of Hypertension Specialist in Clinical Hypertension and has served on the Continuing Medical Education and Nominating Committees of the national society. He has been a member of the regional chapter since 2000 and was elected an at-large member of its board of directors in 2002.

Dr. Prisant, a noninvasive cardiologist, is a 1977 graduate of the MCG School of Medicine and completed his residency and cardiology fellowship at MCG before joining the faculty in 1982.

His first textbook, Hypertension in the Elderly, was just published by Humana Press. He is on the editorial board of Blood Pressure Monitoring, Heart Disease, American Journal of Therapeutics, Journal of Clinical Hypertension and Journal of Clinical Pharmacology. He is a regent of the American College of Clinical Pharmacology and co-chairs the Sphygmomanometer Committee of the Association for the Advancement of Instrumentation.

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