Sevoflurane Preconditioning Limits Intracellular/Mitochondrial Ca2+ in Ischemic Newborn Myocardium

Abstract

The results of this study support the hypothesis that sevoflurane preconditioning protects newborn hearts from calcium overload and ischemic injury via a mechanism dependent on mitochondrial KATP channels.

Sevoflurane preconditioning improves mitochondrial function and long-term neurologic sequelae after transient cerebral ischemia

“…Alternatively, as noted above, opening of mPTP is triggered by the bursts of ROS and calcium, especially during reperfusion. SPC has been demonstrated to significantly decrease mitochondrial ROS accumulation (this study) and calcium overload (44,45). Thus it is possible to account for the SPC-mediated inhibition of mPTP opening merely through its indirect effects, without having to invoke phosphorylation of regulatory protein.…”

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

“…There may be several reasons for this additive effect. One possibility is that delayed SPC caused reduced NF-kB activation on reperfusion, as seen with early SPC [7] and other delayed preconditioning models [23][24][25][26], and that the additional inhibitory effect of parth on NF-kB activation with I/R resulted in an even lower NF-kB activation and resultant reduction in cytokine production [7,10]. Another possibility is that delayed SPC had protective effects via other mechanisms (e.g.…”

“…Delayed SPC, defined as I/R occurring 24-72 h after anaesthetic exposure, appears to have common elements with early SPC [10,16,18,[33][34][35]. Although a reduction in NF-kB activation on reperfusion following ischaemia has not been demonstrated with delayed SPC, it has been shown in other models of preconditioning [23][24][25][26].…”

“…Another possibility is that delayed SPC had protective effects via other mechanisms (e.g. Bcl-2 expression, mitoK ATP channel opening) [10,14,[37][38][39], and that parth had the complementary effect of NF-kB inhibition.…”

“…This is followed by activation of nuclear factor-kB (NF-kB) that leads to synthesis of inflammatory mediators such as tumour necrosis factor-a (TNF-a) and interleukin-1(IL-1) [4][5][6][7][8][9]. Early sevoflurane anaesthetic preconditioning (SPC), defined as brief exposure to the inhalational anaesthetic sevoflurane immediately prior to I/R, is protective against myocardial I/R showing limitation of infarct size and/or reduction in intracellular and mitochondrial Ca 2þ accumulation [10] and lower levels of inflammatory cytokines and NF-kB activation on reperfusion [7]. Although the mechanism of SPC protection is unknown, studies of ischaemic and morphine preconditioning suggest that SPC may result in reactive oxygen species (ROS)-mediated activation of NF-kB prior to I/R, with consequent expression of proteins that are protective following I/R [11,12].…”