Ischemia:

Inadequate blood supply (circulation) to a local area due to complete or partial blockage of the blood vessels to the area.

Reperfusion:

The restoration of blood flow to an organ or tissue. After a heart attack, an immediate goal is to quickly open blocked arteries and reperfuse the heart muscles. Early reperfusion minimizes the extent of heart muscle damage and preserves the pumping function of the heart. Paradoxically, reperfusion also leads to new damage.

Our Focus: Ischemia-Reperfusion Therapy

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.

These events may lead to cell death either by necrosis (i.e., directly from injury to the cells) or by apoptosis (i.e., from an energy dependent cell suicide process) and the formation of an infarct--a region of dead tissue (below). This process may be partially blocked by appropriate therapy.

Re-establishment of blood flow (reperfusion) and re-oxygenation of the affected area is critical to limit irreversible damage. However, reperfusion also brings potentially damaging consequences. This can actually increase the amount of dead tissue (below) due to the release of oxygen radicals and the generation of cellular calcium overload, leading to an acceleration of cellular apoptosis. Again, appropriate therapies may reduce the amount of this "reperfusion injury".

Ischemix has developed cardio protective drugs with dual functions to reduce both pathological calcium entry and oxidation injury, thereby limiting unnecessary cell death. These compounds act through the PI3 kinase pathway to increase phosphorylation of Akt, thus activating a number of downstream pathways that promote cell survival in pro-apoptotic conditions. They are highly effective in validated animal models of cardiac ischemia.