Sci. Aging Knowl. Environ., 19 January 2005
Pay at the Pump
Scans of failing hearts in patients reveal an energy crisis
R. John Davenporthttp://sageke.sciencemag.org/cgi/content/full/2005/3/nf6
Even with a full tank of gas, a car won't run if the fuel doesn't get to the engine. Similarly, a new study reveals that a breakdown in an energy delivery process might spur heart failure. The study uses a new method that tracks metabolism in humans and could provide a novel way to test therapies.
High blood pressure, clogged arteries, and other factors can weaken the heart and sap its power to pump blood throughout the body, a condition known as heart failure. Older people are especially susceptible: 80% of heart failure patients are elderly. Researchers have suspected for decades that heart failure arises because the heart doesn't have enough energy to operate at full strength. Some findings cast blame on defects in creatine kinase. This enzyme crafts adenosine triphosphate (ATP), the cell's energy currency, by stitching a phosphate from phosphocreatine onto another molecule. Crippling the creatine kinase gene in animals depletes their heart energy reserves, and heart tissue sampled from heart failure patients carries reduced amounts of creatine kinase and phosphocreatine. But tissue samples might not accurately reflect the state of a working heart, and researchers would like to watch creatine kinase in action.
Physicist Paul Bottomley of Johns Hopkins University in Baltimore, Maryland, and colleagues had previously developed a new form of magnetic resonance imaging sensitive enough to detect phosphate-containing compounds in the body. (Traditional MRI tracks hydrogen in water, which is more abundant.) They have now used the technique to quantify phosphocreatine and ATP and follow the movement of phosphate between the two compounds in 17 heart failure patients, as well as in healthy subjects. From these data, they calculated how much phosphocreatine the enzyme chugs through as a function of time, a measure known as flux. Flux was half as robust in heart failure patients compared with healthy subjects. The patients carried normal quantities of ATP in the heart, which fits with previous studies revealing that heart failure is associated with only a slight reduction in ATP. Creatine kinase helps truck ATP to the cellular regions where it's needed, and the new findings suggest that a decline in this activity might underlie the apparent energy deficit in failing hearts, say the authors.
"It's beautiful work," says cardiologist Andre Terzic of the Mayo Clinic in Rochester, Minnesota. The ability to image energy molecules in living people is a significant advance, he says: "It goes beyond traditional cardiac biology." The study reveals that failing hearts suffer a significant defect in the main route of energy delivery, adds Terzic. Biochemist Joanne Ingwall of Harvard University says that the approach is a better way to classify heart failure than the traditional method of measuring the volume of blood pumped by the heart and could be used to test new drugs. Such efforts could help get ailing hearts running smoothly again.
January 19, 2005
Science of Aging Knowledge Environment. ISSN 1539-6150