Activation of prosurvival signaling pathways during the memory phase of volatile anesthetic preconditioning in human myocardium: a pilot study

Abstract

According to a compelling body of evidence anesthetic preconditioning (APC) attenuates the deleterious consequences of ischemia-reperfusion and protects the heart through a mechanism similar to ischemic preconditioning. The present study was purported to investigate the intracellular signaling pathways activated in human myocardium in response to a preconditioning protocol with two different volatile anesthetics, namely isoflurane and sevoflurane. To this aim, phosphorylation of PKCα and -δ, ERK1/2, Akt, and GSK3β was determined at the end of the APC protocol, in human atrial samples harvested from patients undergoing open-heart surgery. The results demonstrate that preconditioning with volatile anesthetics triggers the activation of PKCδ and -α isoforms and of prosurvival kinases, ERK1/2, and Akt, while inhibiting their downstream target GSK3β during the memory phase.

Ischemic preconditioning in pigs: a causal role for signal transducer and activator of transcription 3

“…Volatile anesthetics can protect from infarction and increase the phosphorylation of Akt (12,23). We cannot exclude that the use of volatile anesthetics contributes to the increased phosphorylation of Akt at early reperfusion in both I/R and IPC.…”

Possibilities of Pharmacological Preconditioning

“…Ингибирование фосфо-ERK1/2 (центральной MAP-киназы) частично отменя-ет индуцированные изофлураном накопление HIF-1α и нейропротекцию. Изофлуран увеличивает уровень мРНК индуцибельной NO-синтазы [19,20].…”

Exploring the Modulation of Hypoxia-Inducible Factor (HIF)-1α by Volatile Anesthetics as a Possible Mechanism Underlying Volatile Anesthetic-Induced CNS Injury

“…While this has yet to be further explored, the regulation of protein kinase C activity is a potential candidate. Isoflurane and sevoflurane activate multiple isoforms of protein kinase C [58], which itself has been identified as an up-regulator of HIF-1α via inhibition of HIF-1α degradation [59]. Therefore, isoflurane could be regulating HIF-1α via indirectly inhibiting HIF-1α degradation through the translation of protein kinase C. Interestingly, exposure to the intravenous anesthetic propofol results in a reduction of HIF-1α protein levels, possibly via the suppression of HIF-1α accumulation [60] or by inhibiting HREs [61].…”

“…Preconditioning with isoflurane ameliorates neuronal loss from ischemia in rats [65] and, interestingly, dose-dependently prevents neurotoxicity from subsequent prolonged exposure to volatile anesthetics in rat primary cortical neurons and pheochromocytoma neurosecretory cells with overexpression of Alzheimer's mutated presenilin-1 [67]. Importantly, animal research has suggested a role of HIF-1α up-regulation in the mechanisms underlying isoflurane and sevoflurane preconditioning protection in rabbits [57] and rats [58], respectively. Taken together with the aforementioned research, it appears that volatile anesthetics, via the up-regulation of HIF-1α, can be either neuroprotective or neurotoxic, depending on the context in which they are given.…”

“…While the mechanisms by which volatile anesthetics may produce long term alterations in brain functioning have not been established, Jiang and colleagues suggest that mediation of endogenously expressed hypoxia-inducible factor (HIF)-1α may be involved [3]. Indeed, research suggests that volatile anesthetics "hijack" the regulation of HIF-1α pathway [4], which is normally activated under physiological conditions of oxygen deprivation. Therefore, this review explores research in this area in order to demonstrate that the regulation of HIF-1α by volatile anesthetics should be further explored as a possible mechanism underlying volatile anesthetic-induced adverse effects on the CNS.…”