Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Ways to avoid hazards of heart bypass under study

29.08.2005


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



That unfortunate fact has Medical College of Georgia surgeons participating in an international study of a drug that may block the most deadly of these responses in adults who have coronary bypass surgery.

It also has them trying to better understand the process in children whose complex heart defects often mean they spend hours or even days on heart-lung bypass.


“We have to remember that 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 like a major trauma, so our body comes alive with an inflammatory response to circulating through this unit,” Dr. Landolfo says.

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 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 cause 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 than 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.

Toni Baker | EurekAlert!
Further information:
http://www.mcg.edu

More articles from Health and Medicine:

nachricht New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>