Angina drug potentially useful against heart rhythm disorders

In a carefully controlled setting, and with informed consent, researchers gave five patients with the LQT3 mutation an 8-hour intravenous infusion of ranolazine, with ECG and ECHO evaluation before, during, and after treatment. Over the infusion period, the mean reduction in QTc from baseline was 26 +/- 3ms (p<0.0001). This represents about a five percent reduction in the QTc duration, researchers said.

In addition, researchers observed a significant 13 percent shortening in left ventricular isovolumic relaxation time and a significant 25 percent increase in mitral E-wave velocity during the infusion. Both are measures of how well an important chamber of the heart, the left ventricle, relaxes after each heartbeat, enabling it to fill with blood before the next contraction. Past studies have shown that the ability of the ventricle to relax is lessened, not just in Long QT, but also in more common post-heart attack arrhythmias and in conditions including hypertension, coronary artery disease and diabetes. Researchers said that ranolazine was the first treatment to bring about improved ventricular relaxation. No adverse effects of ranolazine were observed.

Cell Circuitry

Atoms and molecules have an undefined property called charge that explains how they behave. Like charges repel each other and opposites attract. Pulling apart two particles that are attracted to each other (separation of charge) creates potential energy that can be put to work. Cells have harnessed charge and potential energy to drive life processes by pumping charged particles into or out of cells.

The buildup of charged particles on one side of a cell membrane (membrane potential) means those particles will rush back if given the chance. That chance comes, under carefully regulated circumstances, with the opening of channel proteins that enable charged particle flow. The flow serves as a switch, kicking on cell functions. In heart muscle cells, for instance, signaling mechanisms coordinate the flow of sodium, potassium and calcium ions to create the potential energy needed for the cells to contract. By contracting in unison, many heart muscle cells bring about the heartbeat. After each heart muscle cell contracts in response to a rush of charged particles, those particles must be pumped back across the membrane to re-create separation of charge (repolarize it), and get it ready for the next contraction, all within milliseconds.

Changes to ion channels, whether caused by disease, aging or LQTS, can cause channel proteins to leak charged particles, which alters the timing of the heartbeat. Ranolazine was found to block late sodium ion current in those patients with mutations of the LQT3 type examined in the current study. The net effect was a significant shortening/improvement of repolarization as measured by QTc duration.