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Ischaemic preconditioning: mechanisms and potential clinical applications

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Abstract

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 protective 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.

Résumé

Objectif

De brefs épisodes d’ischémie, suivis de périodes de reperfusion, accroissent la résistance à un dommage ischémique ultérieur. C’est ce qu’on appelle le «préconditionnement ischémique». En faisant un retour sur la base moléculaire et les principes fondamentaux du préconditionnement ischémique, le présent article fera mieux comprendre à l’anesthésiste et au praticien des soins intensifs les modalités de cette thérapeutique en évolution.

Sources documentaires

Des articles ont été obtenus à partir d’une recherche Medline (1960–1997; recherche de termes: ischémie, lésion de reperfusion, préconditionnement, préconditionnement ischémique, protection cardiaque). Les autres sources comprennent des articles de revues, des monographies, des recherches manuelles (Index Medicus) et une documentation personnelle.

Données principales

Le préconditionnement ischémique est un mécanisme protecteur puissant contre la lésion ischémique qui se produit, selon l’expérience, dans divers systèmes organiques, incluant le coeur; le cerveau, la moelle épinière, la rétine, le foie, les poumons et les muscles squelettiques. Le préconditionnement présente deux effets protecteurs, l’un immédiat et l’autre différé, dont l’importance varie entre les espèces et les systèmes organiques. Quoique les mécanismes exacts des deux composantes protectrices n’aient pas encore été clairement définis, on sait que le préconditionnement ischémique est un processus multifactoriel nécessitant l’interaction de nombreux signaux, de seconds messagers et de mécanismes effecteurs. Des stimuli différents de l’ischémie, comme la perfusion hypoxique, la tachycardie et des agents pharmacologiques, comprenant l’isoflurane, ont des effets similaires au préconditionnement. Le préconditionnement ischémique est actuellement utilisé pendant la chirurgie cardiaque mini-effractive, sans circulation extracorporelle pour protéger le myocarde contre une lésion ischémique lors de l’anastomose.

Conclusion

Le préconditionnement ischémique est un mécanisme protecteur puissant contre les lésions ischémiques dans de nombreux systèmes organiques. Les applications cliniques éventuelles vont dépendre de la clarification des mécanismes biochimiques sous-jacents, de l’évolution des méthodes pharmacologiques d’induction du préconditionnement et des essais contrôlés chez les humains démontrant de meilleurs résultats.

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Correspondence to Eric Jacobsohn.

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Hawaleshka, A., Jacobsohn, E. Ischaemic preconditioning: mechanisms and potential clinical applications. Can J Anaesth 45, 670 (1998). https://doi.org/10.1007/BF03012100

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Keywords

  • Ischemic Precondition
  • Rabbit Heart
  • Ischaemic Precondition
  • Ischaemic Injury
  • Cardiac Protection