Molecular defect found that may cause heart failure

A new study has identified a molecular defect in cardiac cells that may be a fundamental cause of heart failure, a progressive weakening of the heart that leaves the organ unable to pump blood through the body.

The findings, by researchers at the Ohio State University Dorothy M. Davis Heart and Lung Research Institute, show that specialized proteins called ryanodine receptors (RyRs) malfunction in the failing heart. The RyRs form channels that become leaky, leading to calcium imbalances that prevent the heart from contracting effectively and relaxing adequately. The condition worsens until the heart can no longer work as a pump.

The root causes of heart failure are not known.

"We found some drastic changes in the way muscle cells in the failing heart handle calcium," says principal investigator Sandor Gyorke, professor of physiology and cell biology at the OSU Davis Heart and Lung Research Institute. "Discovery of this mechanism suggests at least one potential target for treating the causes of this disease in a rational manner."

Heart failure, also called congestive heart failure, is a disorder in which the heart loses its ability to pump blood efficiently. The term "heart failure" should not be confused with cardiac arrest, a situation in which the heart actually stops beating.

Causes, incidence, and risk factors

Heart failure is almost always a chronic, long-term condition, although it can sometimes develop suddenly. This condition may affect the right side, the left side, or both sides of the heart.

As the heart's pumping action is lost, blood may back up into other areas of the body:
More information: Congestive heart failure

Currently, the only way to correct heart failure is by heart transplantation.

About 4.9 million Americans are currently living with heart failure, and an estimated 265,000 of them die of it yearly. Those with the condition are at six to nine times greater risk of experiencing sudden cardiac death than someone in the general population. From 1992 to 2002, deaths from heart failure rose 35% and the incidence is expected to keep rising.

Calcium plays a fundamental role in muscle contraction, particularly in heart muscle. A heart contraction begins when the heart's pacemaker sends an electrical signal to heart-muscle cells. The electrical signal triggers the release of calcium from a large storage site within each muscle cell. The released calcium activates the muscle cell's contractile machinery, which causes the cell, and the heart as a whole, to contract.

This calcium storage site is known as the sarcoplasmic reticulum (SR), and it resembles a convoluted, flattened sack within the cell. The delicate, membrane-bound walls of the SR are penetrated with thousands of RyR channels. These serve as gate keepers that allow calcium to flood into the cell to initiate contraction.