Preconditioning - endogenous defence mechanisms of the heart

The term 'preconditioning' refers to the paradoxical phenomenon that pretreatment with a potential noxious stress-stimulus can increase cellular tolerance to subsequent noxious stress-stimuli. This was first described in an experimental model in dogs in which short-lasting periods of myocardial ischemia resulted in reduced infarction during a subsequent long-lasting coronary artery occlusion. Similar observations have also been made in other species and in other organs. During the last few years, the term preconditioning has been expanded to include pretreatment with other physical stress-stimuli or pharmacological agents that can increase cellular resistance to injury. The phenomenon probably represents a general adaptive response to cellular stress, but mechanisms involved are not fully clarified. This review focuses on preconditioning in the heart. Firstly, we want to address the observation that activation of endogenous defence mechanisms can increase cellular tolerance to several potentially noxious stimuli. Based on results from experimental research, we will give an overview of intracellular mechanisms that is currently in focus. Secondly, we want to address the potential role of preconditioning in clinical practice. We will present results from studies in patients with coronary artery disease and discuss possible clinical implications. Results show that the phenomenon probably exists in the human myocardium. In the future, this might be exploited in patients with acute coronary syndromes, especially since advanced techniques are now available for acute revascularization. Additionally, identification of possible mechanisms involved may influence the choice of medical treatment in high-risk patients with stable coronary artery disease. Preconditioning can also be exploited during elective surgical procedures. This should be of great interest, as the extent of elective surgery in patients at high-risk for coronary events is increasing. In this respect it is important to note that opioid-receptors are probably involved in preconditioning in humans. The last part of this review will address the possible relation between preconditioning and different anesthetic agents and sedatives.