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Combining antioxidants with a severe chest pain drug
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PostPosted: Tue Jul 11, 2006 6:10 pm    Post subject: Combining antioxidants with a severe chest pain drug Reply with quote

Source: Ohio State University Released: Tue 11-Jul-2006, 09:00 ET

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Twist on Chest Pain Drug Improves Heart Attack Outcome
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HEART ATTACK BLOOD FLOW TRIMETAZIDINE TMZ
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A new study in rat hearts suggests that combining antioxidants with a
drug used to treat severe chest pain may help improve how a heart
recovers from a heart attack.



Newswise - A new study in rat hearts suggests that combining
antioxidants with a drug used to treat severe chest pain may help
improve how a heart recovers from a heart attack.

The primary goal after a heart attack is to return blood flow to
blocked arteries as quickly as possible. But that sudden blood flow, or
reperfusion, could further damage the tissue surrounding those
arteries.

"This sudden rush of blood through vessels that are used to little or
no blood flow creates a burst of cell-damaging free radicals," said
Periannan Kuppusamy, a study co-author and a professor of internal
medicine at Ohio State University.

Results showed that the rat hearts pre-treated with antioxidant-laced
medications actually functioned better and had less tissue damage
during reperfusion.

"That's because antioxidants scavenge free radicals that flourish
during reperfusion," Kuppusamy said.

The results appear in a recent issue of The Journal of Pharmacology and
Experimental Therapeutics. The study's lead author, Vijay Kutala, is
a research scientist at the Davis Heart and Lung Research Institute at
Ohio State.

The researchers treated rat hearts with trimetazidine (TMZ), a drug
given to people with angina, or severe, chronic chest pain. TMZ is an
anti-ischemic drug, meant to decrease oxygen use and reduce tissue
damage caused by the blockage of blood flow, or ischemia, in vessels.

Kuppusamy said that while TMZ is used extensively throughout Europe,
the drug is not approved for use in the United States. Yet very similar
drugs are used to treat angina in this country, including propranalol
(brand name Inderal) and nifedipine (Procardia).

The researchers created two new forms, or derivatives, of TMZ by
combining the drug with one of two types of chemical-based
antioxidants. They called the derivatives TMZ-NH and TMZ-?NH.

Hearts were surgically removed from the rats. The researchers then
placed each heart in its own small glass tube, and continuously
injected, or perfused, a solution of nutrients through the hearts to
keep them pumping.

Rat hearts were separated into four groups: one group received TMZ
only, another group received TMZ-NH, and the hearts in the last
treatment group were treated with TMZ- ?NH. Rat hearts used as controls
weren't treated with any medication.

TMZ or one of its antioxidant derivatives was injected into a heart for
one minute. After the injection, the researchers stopped the flow of
the nutrient solution. After 30 minutes of blocked blood flow, the
solution injections were started again, and continued for 45 minutes.

The researchers had measured the flow of solution through each rat
heart before the blood flow was halted and again during reperfusion.

Results showed that pre-treatment with the derivatives TMZ-NH and
TMZ-?NH was most effective at protecting hearts from injury by
subsequent reperfusion. TMZ alone offered some protection from tissue
damage during reperfusion, but not to the degree of the antioxidant
derivatives.

Free-radical levels were about 50 percent higher in both the control
hearts and rat hearts treated with TMZ, compared to the level in hearts
treated with the antioxidant derivatives. Also, the area of
irreversible tissue damage, called an infarct, was substantially
smaller - about half the size - in the hearts treated with the
antioxidants.

"These hearts were stronger and healthier overall - they were
better able to contract and therefore better able to accommodate the
flow of the solution during reperfusion," Kuppusamy said. "Both the
blood pressure and flow of the nutrient solution were greatly improved.

"Several studies have shown that it is possible to prevent much of
the free-radical damage caused by reperfusion," Kuppusamy said.
"Combining antioxidants with a drug already used to treat ischemia
could be an efficient way to improve the outcome of a heart attack."

Kuppusamy and Kutala co-authored the study with colleagues from the
Davis Heart and Lung Research Institute at Ohio State, and with the
Institute of Organic and Medicinal Chemistry at the University of
Pécs, in Pécs, Hungary.




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