Hopkins Finding Could Lead To Development Of Better Cardioprotective Drugs
Researchers at Johns Hopkins have come one step closer to understanding the chain of events that protects the heart against injury during a heart attack, paving the way for the development of a new class of drugs to treat people at risk.
The team has found that tiny, energy-dependent channels within mitochondria -- the sacs of enzymes that act as powerhouses of cells -- may play a significant role during "preconditioning," a process in which brief coronary blood flow stoppages that precede a major heart event protect the heart against severe damage. Mitochondria convert carbohydrate energy into ATP (adenosine triphosphate), the type of energy needed for such functions as muscle contraction.
Using rabbit heart cells, the researchers found that the blood pressure medicine diazoxide opened up channels in the cell membranes that let potassium flow into the cells. The drug opened the potassium channels in the mitochondria but had no effect on other channels. The team also found that when oxygen supply to the heart cells was stopped, as happens during a heart attack, diazoxide halved the rate of cell death.
Results of the study, supported by the National Institutes of Health, were published in the June 30 issue of Circulation: Journal of the American Heart Association. "During periods of ischemia, or lack of blood flow, cells lose energy and die," says Eduardo Marban, M.D., Ph.D., director of molecular and cellular cardiology at Hopkins and senior author of the study. "If we could keep the energy levels high during heart failure or a heart attack, we could buy time. While we're still not sure how opening these mitochondrial channels might protect heart cells from dying, we know that their role is crucial. This will help in developing a more effective class of cardioprotective drugs.
"There is good reason to believe that, if we were able to recruit the preconditioning process, death and suffering from heart attacks could be cut dramatically -- perhaps by more than 50 percent."
The study's other authors were Toshiaki Sato, M.D., Ph.D., and Brian O'Rourke, Ph.D., of Hopkins; and Yongge Liu, Ph.D., of Otsuka America Pharmaceutical Inc., Rockville, Md.
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