Arrhythmia:

A disturbance of the normal heart rhythm. Atrial fibrillation is an arrhythmia which frequently occurs after cardiac surgery.

Anoxia:

The absence or near absence of oxygen.

Infarction:

Region of dead muscle cells tissue resulting from ischemia and reperfusion injury.

Atherosclerotic plaque:

A buildup of cholesterol and mineral calcium inside the wall of an artery.

 

The Heart Failure Cycle

A heart attack is usually caused by blockage of an artery. The heart muscle beyond the block is then deprived of oxygen and essential nutrients. This ischemia (literally "lack of blood flow") leads to many damaging changes, including calcium buildup in cells, high levels of reactive oxygen species ("ROS"), buildup of waste products such as lactic acid, and general energy depletion.

Narrowing of a coronary artery slows blood flow to the muscle beyond. A clot or bit of loosened atherosclerotic plaque may completely block the vessel (top of cycle).

The slowed blood flow (ischemia) leads to oxygen and nutrient depletion. Cellular calcium overload and oxidative damage follow. Muscle cells begin to die with attendant arrhythmia and myocardial infarction. The reduced pumping action further limits blood supply to the muscle and the heart failure cycle continues in a downward spiral, with more calcium overload and more oxidative damage.

Bypass surgery and the heart-lung machine requires clamping of vessels on the heart, resulting in ischemia. Further, plaque may be dislodged, leading to blockage of flow both in the heart and distant organs. These surgical risks can lead to new myocardial infarction and cardiac arrhythmias. Prevention requires targeting both calcium overload and oxidative damage. Unlike traditional single target drugs, Ischemix leading compound CMX-2043 has been designed as a dual-function hybrid molecule with both calcium-regulating and anti-oxidant properties.