Extracardiac approaches to protecting the heart☆

Abstract

Myocardial adaptation to ischemia in the form of ischemic preconditioning is clinically attractive, but not easily usable in cardiac surgery until molecular mimics are discovered. The various forms of pre- and postconditioning, including remote preconditioning, indicate that a 'universal' protection is evoked. A growing body of evidence indicates that events underlying myocardial adaptation to ischemia may either involve, or be parallel to, signaling of the innate immune response. The heart can be protected through giving cytokines or fragments of bacterial walls. A possible role for cytokines, Toll-like receptors, and nuclear factor kappa B for evoking ischemic preconditioning are discussed. Through stimulating innate immunity, there is potential to bring preconditioning into the clinics in a reasonable time frame. Other approaches to myocardial protection, using cell transfer, gene therapy, and microRNA, are briefly commented on.

Remote Transplantation of Mesenchymal Stem Cells Protects the Heart Against Ischemia-Reperfusion Injury

“…Ischemic conditioning is an endogenous way to protect the heart from ischemia‐reperfusion injury using repetitive brief episodes of ischemia, evoking myocardial protection when applied either locally or distantly . Expanding upon the principle of remote therapy to protect the heart, gene therapy through delivery of DNA to peripheral organs has been performed successfully.…”

Protecting the heart through delivering DNA encoding for heme oxygenase-1 into skeletal muscle

“…However, efficient and safe gene delivery to targeted cells in the heart in vivo is still an unresolved enigma. Genes can be injected to the heart directly into the myocardium, delivered through the coronary arteries or veins, or into the pericardium (Valen, 2009). Of those options a direct myocardial injection is the approach most likely to succeed (Valen, 2009).…”

“…Genes can be injected to the heart directly into the myocardium, delivered through the coronary arteries or veins, or into the pericardium (Valen, 2009). Of those options a direct myocardial injection is the approach most likely to succeed (Valen, 2009). However, this is an invasive procedure due to the hearts' protective placement in the thorax and is thus unlikely to represent a large-scale clinical treatment.…”

Cardiac conditioning: a review of evolving strategies to reduce ischaemia-reperfusion injury

“…Early studies involving the anti-C5 complement agent did demonstrate a mortality benefit (1.8% vs 5.9%, p=0.01)26 27; however, the subsequent APEX MI trial found no differences in mortality or composite end points 28. Increased knowledge of cytokine and chemokine pathways in the reperfusion response may identify novel modifiable targets for innovative therapeutic agents aimed at amplifying the benefits of reperfusion therapy 29 30…”