Safety of Popular Clot Buster Questioned

Researchers at Weill Cornell Medical College (New York, NY, USA) examined genetically engineered mice whose cardiac nerve cells did not generate t-PA. The mice had greatly subdued sympathetic nervous systems when stimulated by an electrical field, and their hearts also failed to produce the spike in norepinephrine seen in normal mice when they were placed under electrical field stimulation. Significantly, mice without functioning t-PA also had much lower rates of arrhythmia when subjected to ischemia and reperfusion compared to normal mice.

The researchers noted that the results may explain the excess risk for dangerous and even fatal arrhythmias in heart attack patients who have received t-PA, and also support the notion that t-PA release by cardiac nerve cells is a prime culprit in cardiac arrhythmias associated with heart attack. The findings were published in the September 2006 edition of the Journal of Experimental Medicine.

"In some cases, using this drug might make matters worse,” said lead author Dr. Roberto Levi, a professor of pharmacology at Weill. "Still, our finding does raise intriguing new questions about this therapy. It also opens a new window into the mechanisms behind arrhythmia, suggesting possible new therapeutic targets.”

T-PA is a secreted serine protease, which converts the proenzyme plasminogen to plasmin, a fibrinolytic enzyme that is secreted by the endothelial cells lining blood vessels and by nerve cells in and around the heart. T-PA remains one of the few effective, widely available weapons emergency room teams have when battling stroke and heart attack.



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