Myocardial preconditioning and cardioprotection by volatile anaesthetics

Abstract

The biological bases and the clinical applications of ischaemic and anaesthetic preconditioning are reviewed. Ischaemic preconditioning is an endogenous defensive phenomenon of the myocardium in which brief periods of ischaemia followed by reperfusion reduce the infarct size induced by longer ischaemic stimuli; both an early and a late phase may be distinguished. In the early phase, the mediators released activate ATP-dependent potassium channels and kinase cascade; these enzymes migrating at the level of various subcellular structures phosphorylate some end-effectors responsible for cardioprotection. Several molecules that are involved in the regulation of cell death during ischaemia-reperfusion injury have been proposed for such a role, including mitochondrial ATP-dependent potassium channels, connexins and cytoskeletal and mitochondrial proteins. In the late phase, the triggers and mediators themselves, plus nitric oxide, are responsible for the genetic reprogramming providing a protective effect via ex-novo synthesis of proteins. Volatile halogenated anaesthetics may induce a particular sort of pharmacological preconditioning, anaesthetic preconditioning, which presents some differences in the biochemical signalling mechanism but is able to give protection comparable to the ischaemic form. Anaesthetic preconditioning presents obvious advantages compared to ischaemic preconditioning, and researchers have tried to take advantage of this in the clinical setting, in cardiac surgical patients, in neuroprotection and to prolong the survival of organs destined for transplantation.

Caveolin-3 expression and caveolae are required for isoflurane-induced cardiac protection from hypoxia and ischemia/reperfusion injury

“…In addition, volatile anesthetics modulate ATP-sensitive potassium channel activity [32,33], the generation of reactive oxygen species, and mitochondrial permeability transition pore opening [36]. Of note, many of those signaling molecules and effector systems can either interact directly with the scaffolding domain of caveolin or are known to localize to caveolae [16,17,37].…”

“…Cardiac myocytes (CM) express the muscle-specific isoform caveolin-3 [12] while other cell types in the heart express caveolin-1 and -2. Recent studies have shown: 1) the presence and interaction of all three caveolin isoforms in adult cardiac myocytes [13,14], 2) a signaling role for caveolin-1 in cardiac myocytes [15], and 3) that caveolins can scaffold proteins associated with cardiac protection [16,17].…”

Brain death and its implications for management of the potential organ donor

“…133 Volatile anesthetics (sevoflurane, isoflurane, and desflurane) have, in several experimental and clinical settings, been shown to protect the heart from I/R injury. [134][135][136][137] Recently, isoflurane was demonstrated to have a similar effect on the rat liver, 138 and sevoflurane, in a prospective randomized study, protected the human liver from I/R injury during liver resection. 139 It is our practice to administer volatile anesthetics at least during the last 30 min before aortic cross clamping.…”

Nuclear factor-κB inhibition provides additional protection against ischaemia/reperfusion injury in delayed sevoflurane preconditioning

“…Delayed anaesthetic preconditioning, defined as an I/R injury limiting effect 24-72 h after the initial anaesthetic exposure, has been demonstrated in multiple models [16,17] and appears to share many of the mechanisms of early anaesthetic preconditioning [18,19]. Although not demonstrated with anaesthetic preconditioning, other models of preconditioning have shown increased activation of NF-kB by a preconditioning stimulus [12,[20][21][22] and decreased NF-kB activity following renal and cardiac I/R [23][24][25][26].…”