Pacing Postconditioning: Recent Insights of Mechanism of Action and Probable Future Clinical Application

Ischemic heart disease, also known as coronary heart disease or coronary artery disease, accounts for >50% of cardiovascular events and is a leading cause worldwide of morbidity and mortality. Hypoperfusion of the heart is the major cause of injury in ischemic heart disease, as it results in the death of cardiomyoctes due to a lack of oxygen and energy. This injury ultimately leads to a dead area in the heart called infarcted area or myocardial infarction. The formation of myocardial infarction leads to a lengthy process of remodeling which causes many changes in the architecture and the electrophysiology of the heart. These changes may eventually lead to death due to arrhythmia or heart failure. Tremendous efforts have been made over the last decades to decrease the burden of ischemic reperfusion (I/R) injury. The first salvage to the ischemic heart is reperfusion; however, this procedure is associated with a subsequent reperfusion injury. In the 1980s, a method known as preconditioning was introduced and showed great potential in combating ischemic heart disease, but this technique is limited by the difficulty of its translation to the clinic as it requires the anticipation of an occurrence of ischemic heart disease. Not long after, a new method, postconditioning, was introduced. This method showed great success, and several studies were performed to investigate its signaling cascades and the possibility of its translation to the clinic. Thereafter, several trials were made, and many methods of postconditioning were developed. One of these is intermittent dyssynchrony, pacing postconditioning (PPC), of the heart, which involves brief episodes of electrical pacing. PPC afforded a pronounced protection to the heart against I/R injury, similar to that afforded by pre- and postconditioning.