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(Last updated 7/10/06)

Previous stories pertaining to Professor Kuppusamy's research:

"Twist On Chest Pain Drug Improves Heart Attack Outcome," 2/15/06.

TWIST ON CHEST PAIN DRUG IMPROVES HEART ATTACK OUTCOME

COLUMBUS , Ohio – 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.

Periannan Kuppusamy
Vijay Kutala

“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).


“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. Both the blood pressure and flow of the nutrient solution were greatly improved."


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-FNH.

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- FNH. 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-FNH 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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Contact: Periannan Kuppusamy, (614) 292-8998; Kuppusamy.1@osu.edu

Written by Holly Wagner, (614) 292-8310; Wagner.235@osu.edu