Ischaemic preconditioning: mechanisms and potential clinical applications

Purpose: Brief ischaemic episodes, followed by periods of reperfusion, increase the resistance to further ischaemic damage. This response is called "ischaemic preconditioning." By reviewing the molecular basis and fundamental principals of ischaemic preconditioning, this paper will enable the anaesthetic and critical care practitioner to understand this developing therapeutic modality. Source: Articles were obtained from a Medline review (1960-1997: search terms: ischaemia, reperfusion injury, preconditioning, ischaemic preconditioning, cardiac protection). Other sources include review articles, textbooks, hand-searches (Index Medicus), and personal files. Principle finding: Ischaemic preconditioning is a powerful mechanism against ischaemic injury that has been shown to occur in a variety of organ systems, including the heart, brain, spinal cord, retina, liver, lung and skeletal muscle. Ischaemic preconditioning has both immediate and delayed protective effects, the importance of which varies between species and organ systems. While the exact mechanisms of both protective components are yet to be clearly defined, ischaemic preconditioning is a multifactorial process requiring the interaction of numerous signals, second messengers and effector mechanisms. Stimuli other than ischaemia, such as hypoxic perfusion, tachycardia and pharmacological agents, including isoflurane, have preconditioning-like effects. Currently ischaemic preconditioning is used during minimally invasive cardiac surgery without cardiopulmonary bypass to protect the myocardium against ischaemic injury during the anastomosis. Conclusion: Ischaemic preconditioning is a powerful protective mechanism against ischaemic injury in many organ systems. Future clinical applications will depend on the clarification of the underlying biochemical mechanisms, the development of pharmacological methods to induce preconditioning, and controlled trials in humans showing improved outcomes.