Cardioprotection by remote ischemic conditioning and its signal transduction

Cardioprotective strategies aim to salvage myocardium from ischemia/reperfusion injury and to reduce infarct size and its consequences. Different stimuli, acting at sites remote from the heart (remote conditioning), activate molecular self-defense mechanisms at the target organ heart as well as in other parenchymal organs. Remote conditioning of the heart has been established in many experimental studies and successfully translated to patients. Remote ischemic conditioning by short repetitive cycles of ischemia/reperfusion on an extremity reduces infarct size and improves the prognosis of patients with reperfused myocardial infarction. The present review focuses on three levels of remote conditioning and its resulting cardioprotection: I) at the stimulus level, electrical stimulation, chemical/pharmacological substances, mechanical trauma and cycles of ischemia/reperfusion act at sites remote from the heart, II) at the transfer level, neuronal and humoral mediators transfer the protective signal from the periphery to the heart, and III) at the target level, receptor activation and intracellular signal transduction ultimately affect protection of the myocardium and other organs, as established in different animal models and humans/patients. Remote conditioning is obviously a systemic response. Further mechanistic understanding is mandatory to translate the protection by remote conditioning more successfully to patients with cardiovascular disease.