Dr. Xie, a molecular biologist, is a basic scientist. He approached heart failure by looking at the behavior of a tiny doorway found in cell surfaces - a pump, actually, that controls the levels of calcium in the cell, and thereby controls the strength of each heart beat.
Dr. Xie found that the pump is more than a pump. It has a second, completely distinct role in the cell. It is a commander. It can issue instructions to the rest of the cell, and get all kinds of processes moving.
As Dr. Xie looked at how the pump also sends signals, he realized that this meant a class of drugs given to heart failure patients for nearly 200 years - digitalis and drugs like it - probably didn't work the way everyone thought.
"When we started to look at the therapeutic effect of digitalis on cardiac cells, we realized the concentration [of digitalis] we used was too low," Dr. Xie said. There wasn't enough digitalis to affect pumping. Dr. Xie discovered that drugs like digitalis actually turn on the pump's command capabilities. Drs. Shapiro and Xie conducted a series of four experiments to look at how digitalislike substances affect the rat heart. In one experiment, they gave healthy rats low doses of a digitalislike drug. Those rats developed fibrous hearts, which worked inefficiently. They were in heart failure. In another experiment, they gave heathy rats an antibody to block digitalislike drugs, then they injected a digitalislike drug into the rat. The antibody proved protective. Those rat hearts had far less fiber. In a third experiment, they induced kidney disease in rats. These rats developed hearts riven with fibrous tissue, incapable of relaxing completely, and therefore inefficient at refilling. Finally, they gave the rats with experimentally induced kidney disease an antibody to block digitalislike substances. Those rats had far less fibrous tissue. "That study was an eye-opener," Dr. Shapiro said. "It was a smoking gun implicating [digitalislike drugs] in fibrosis."
Tags: Heart Failure, digitalis, kidney failure, Kr. Xie, Molecular Biology
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