The mechanisms of cardio-protective effects of desflurane and sevoflurane at the time of reperfusion: anaesthetic post-conditioning potentially translatable to humans?

Abstract

Myocardial conditioning is actually an essential strategy in the management of ischaemia-reperfusion injury. The concept of anaesthetic post-conditioning is intriguing, its action occurring at a pivotal moment (that of reperfusion when ischaemia reperfusion lesions are initiated) where the activation of these cardio-protective mechanisms could overpower the mechanisms leading to ischaemia reperfusion injuries. Desflurane and sevoflurane are volatile anaesthetics frequently used during cardiac surgery. This review focuses on the efficacy of desflurane and sevoflurane administered during early reperfusion as a potential cardio-protective strategy. In the context of experimental studies in animal models and in human atrial tissues in vitro, the mechanisms underlying the cardio-protective effect of these agents and their capacity to induce post-conditioning have been reviewed in detail, underlining the role of reactive oxygen species generation, the activation of the cellular signalling pathways, and the actions on mitochondria along with the translatable actions in humans; this might well be sufficient to set the basis for launching randomized clinical studies, actually needed to confirm this strategy as one of real impact.

Cardioprotection with halogenated gases: how does it occur?

“…The mechanism by which this effect is produced is directly related to drug PreC and PostC 59,62,89. The pathways involved in both types of conditioning have numerous points in common 115.…”

“…During reperfusion, the calcium overload, massive production of free ROS, by the mitochondria and destruction of the capacity of cellular oxidative phosphorylation induce the opening of MPTPs 88,89. During ischemia, the reduction in ATP concentrations and increase in phosphate concentrations sensitize the mitochondria to the opening of MPTPs, which is usually compensated by the reduction in intracellular pH, which prevents its opening.…”

“…These receptors are coupled with G proteins, and their stimulus generates an intracellular cascade through second messengers, which ultimately leads to cell protection through an end effector 89. The intracellular pathways of the second messengers involved are the reperfusion injury-salvage kinase (RISK) pathway and the survivor-activating factor-enhancement (SAFE) pathway, and the end effector in which both converge is the mitochondria (mitochondrial permeability transition pore [MPTP]) 91.…”

“…The p70s6K protein inhibits the activation of GSK3β. NO (produced by NOS), and GSK3β inhibits the opening of the MPTP 89. NO has a double-cardioprotective effect, due to its direct effects of vasodilation and anti-inflammation and its indirect effects of inhibiting GSK3β and opening K ATP channels, which stabilizes the mitochondrial membrane, decreasing cellular Ca 2+ overload and inhibiting the opening of the MPTP 103…”

“…Moreover, PostC induced by desflurane and sevoflurane has antiapoptotic effects, due to the preservation of mitochondrial integrity through the inhibition of the opening of the MPTP 89. The activation of PI3K/Akt and ERK1/2 regulates expression of SUR2A, which seems to be a crucial cardioprotective protein 104…”