New Findings Point To Use Of Antioxidant Vitamins To Improve Cardiac Patient Outcomes

June 07, 1997

Recent headlines have trumpeted the research news that antioxidant vitamins -- notably vitamin E -- appear to protect against many of the diseases associated with aging, including cardiovascular diseases and some types of cancer. The power of the antioxidant compounds is thought to lie in their ability to quell the activity of volatile molecules called free radicals, limiting the corrosive damage they inflict on tissues of the body.

Now, scientists at the University of Pennsylvania Medical Center have shown that free-radical injury also likely occurs following heart bypass surgery or treatment for a heart attack during the critical period of reperfusion, when blood flow is restored to the heart muscle. Paradoxically, serious dysfunction or failure of the heart often occurs in this period of renewed blood supply, a fact that has frustrated doctors and surgeons caring for these patients. The findings appear in the June 3 issue of Circulation.

Using a new noninvasive, quantitative test developed at Penn and first reported last year, the researchers precisely documented sharp spikes in free-radical activity following reperfusion, suggesting oxidant stress as a cause for the heart's negative response during this phase of cardiac treatment. Such a link has been long been suspected, but has never before been conclusively demonstrated. The same test will allow the investigators to develop specific pre- operative therapies with antioxidant vitamins or drugs to see if these mitigate the process.

"Using this approach, we can rationally evaluate precise doses of antioxidant vitamins or drugs with the aim of suppressing the free-radical mechanism during reperfusion and then seeing whether there are benefits for patients," explains Garret A. FitzGerald, MD, chairman of the department of pharmacology and senior author on the study. "Once we've defined the appropriate doses, we will be able to assess whether giving these compounds before surgery leads to improved outcomes."

The test developed by FitzGerald and his colleagues use gas chromatography and mass spectrometry to measure urinary levels of a biochemical called 8-epi PGF2-alpha, which is a stable end product resulting from free-radical-catalyzed attack on arachidonic acid. Arachidonic acid is a fatty acid, a kind of specialized lipid, that is a normal constituent of cell membranes throughout the body.

Several experiments are described in the current paper, including a set of three clinical studies conducted at Mater Hospital in Dublin, Ireland, during FitzGerald's time there, and at the Hospital of the University of Pennsylvania. In the first, urinary levels of 8-epi PGF2-alpha were characterized in groups of normal volunteers. In the second, 20 healthy volunteers and 20 patients with stable angina were compared with 12 patients presenting with acute myocardial infarction who were then treated with the clot- busting drug streptokinase. In the heart-attack patients, urinary levels of 8-epi PGF2-alpha jumped immediately following this thrombolysis treatment -- i.e., during the period of reperfusion -- to more than 2-1/2 times those of the other two groups, whose levels were similar to each other. In the third clinical study, urinary levels of 8-epi PGF2- alpha were assessed in five patients prior to, during, and after elective coronary artery bypass graft surgery. During reperfusion, levels of 8-epi PGF2-alpha nearly tripled over the preoperative baseline. Twenty-four hours after surgery, levels had returned to normal.

"What we found is that, in clinical settings of reperfusion, specifically in people undergoing bypass surgery and in people given thrombylitic drugs to treat myocardial infarction, we see a pronounced elevation of this biochemical marker of oxidant stress," FitzGerald says.

Funding for the study was provided by the Wellcome Trust, the Health Research Board of Ireland, the Irish Heart Foundation, and the National Institutes of Health.

The University of Pennsylvania Medical Center's sponsored research ranks fifth in the United States, based on grant support from the National Institutes of Health, the primary funder of biomedical research in the nation -- $149 million in federal fiscal year 1996. In addition, for the second consecutive year, the institution posted the highest growth rate in its research activity -- 9.1 percent -- of the top ten U.S. academic medical centers during the same period. Penn news releases are available to reporters by direct e-mail, fax, or U.S. mail, upon request. They are also posted electronically to EurekAlert! (http://www.eurekalert.org), an Internet resource sponsored by the American Association for the Advancement of Science.
-end-


University of Pennsylvania School of Medicine

Related Heart Attack Articles from Brightsurf:

Top Science Tip Sheet on heart failure, heart muscle cells, heart attack and atrial fibrillation results
Newly discovered pathway may have potential for treating heart failure - New research model helps predict heart muscle cells' impact on heart function after injury - New mass spectrometry approach generates libraries of glycans in human heart tissue - Understanding heart damage after heart attack and treatment may provide clues for prevention - Understanding atrial fibrillation's effects on heart cells may help find treatments - New research may lead to therapy for heart failure caused by ICI cancer medication

Molecular imaging identifies link between heart and kidney inflammation after heart attack
Whole body positron emission tomography (PET) has, for the first time, illustrated the existence of inter-organ communication between the heart and kidneys via the immune system following acute myocardial infarction.

Muscle protein abundant in the heart plays key role in blood clotting during heart attack
A prevalent heart protein known as cardiac myosin, which is released into the body when a person suffers a heart attack, can cause blood to thicken or clot--worsening damage to heart tissue, a new study shows.

New target identified for repairing the heart after heart attack
An immune cell is shown for the first time to be involved in creating the scar that repairs the heart after damage.

Heart cells respond to heart attack and increase the chance of survival
The heart of humans and mice does not completely recover after a heart attack.

A simple method to improve heart-attack repair using stem cell-derived heart muscle cells
The heart cannot regenerate muscle after a heart attack, and this can lead to lethal heart failure.

Mount Sinai discovers placental stem cells that can regenerate heart after heart attack
Study identifies new stem cell type that can significantly improve cardiac function.

Fixing a broken heart: Exploring new ways to heal damage after a heart attack
The days immediately following a heart attack are critical for survivors' longevity and long-term healing of tissue.

Heart patch could limit muscle damage in heart attack aftermath
Guided by computer simulations, an international team of researchers has developed an adhesive patch that can provide support for damaged heart tissue, potentially reducing the stretching of heart muscle that's common after a heart attack.

How the heart sends an SOS signal to bone marrow cells after a heart attack
Exosomes are key to the SOS signal that the heart muscle sends out after a heart attack.

Read More: Heart Attack News and Heart Attack Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.