Ischaemic Preconditioning Protects Against Ischaemia/Reperfusion Injury: Emerging Concepts

Abstract

IP utilises endogenous mechanisms in skeletal muscle, liver, lung, kidney, intestine and brain in animal models to convey varying degrees of protection from I/R injury. To date there are few human studies, but recent reports suggest that human liver, lung and skeletal muscle acquire similar protection after IP. Specifically, preconditioned tissues exhibit reduced energy requirements, altered energy metabolism, better electrolyte homeostasis and genetic re-organisation, giving rise to the concept of 'ischaemia tolerance'. IP also induces 'reperfusion tolerance' with less reactive oxygen species and activated neutrophils released, reduced apoptosis and better microcirculatory perfusion compared to non-preconditioned tissue. Systemic I/R injury is also diminished by preconditioning. IP is ubiquitous but more research is required to fully translate these findings to the clinical arena.

Pré-condicionamento isquêmico por oclusão seletiva da artéria pulmonar em ratos

“…This protective effect is due to what has been designated I/R tolerance. (11) Since the results of various studies in those studies, IPC was performed using total hilar clamping. In a model of isolated perfusion, another group of authors (24) observed the effect of IPC on lung compliance and on gas exchange by stopping the perfusion (for 5 or 10 min) with or without simultaneous respiratory arrest.…”

“…This appears to confer protection against later, longer ischemic episodes and the resulting reperfusion injury. This strategy has been studied in many organs and tissues, such as the heart, kidney, liver, intestine, brain, skeletal muscle and lung, (11) in animal models as well as in clinical studies. (12) In most lung studies, IPC was achieved through total hilar clamping, which does not correspond to the clinical reality of transplantation, in which the pulmonary artery is isolated for clamping separately from the other hilar structures.…”

From the S.P. Botkin’s idea of “preexposure” to preconditioning phenomenon. Perspectives for use of phenomena of ischemic and pharmacological preconditioning

“…Первоначально к защитному действию ИП от-носили только уменьшение размеров инфаркта, впоследствии оно было распространено на вос-становление в постишемическом периоде функ-циональной активности органов [66]. Уменьшение реперфузионных повреждений миокарда на фоне ишемического прекондиционирования еще называ-ют посткондиционированием [83]. Гипоксическое посткондиционирование по сути является новым способом реабилитации функционального состоя-ния органов (мозга, сердца) после тяжелых повреж-дающих воздействий гипоксического генеза.…”

Harnessing the preconditioning phenomenon: does remote organ ischaemia provide the answer?

“…There is an early ''classical'' period of protection occurring almost immediately after the ischaemic stimulus, followed by a ''late preconditioning'' phase, starting 12-42 hours later. 6 The exact mechanisms by which these adaptive changes are mediated remain unknown. Early preconditioning appears to be conducted through a pathway activated by a variety of substances released during ischaemia and reperfusion, such as adenosine, bradykinin, and opioids.…”