Definitions
Ischemia:
Inadequate blood supply (circulation) to a local area due to complete or partial blockage of the blood vessels to the region.
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.
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 (figure 1).
Figure 1: Ischemia
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 due to the release of oxygen radicals and the generation of cellular calcium overload, leading to an acceleration of cellular apoptosis (figure 2).
Figure 2: Reperfusion
Activation of proteins in the Reperfusion Injury Salvage Kinase (RISK) pathway can provide cardioprotection during myocardial reperfusion. Ischemix has developed compounds that act through the PI3 kinase pathway to increase phosphorylation of Akt, thus activating the RISK pathway. Activation of the RISK pathway reduces cellular calcium overload and other manifestations of ischemia reperfusion.
The known active natural component of CMX-2043 itself is a potent anti-oxidant with the ability to enhance recycling of intracellular oxygen-radical regulators. CMX-2043 appears to have greater potency as an antioxidant than the natural component.