Protective effect of sevoflurane on myocardial ischemia-reperfusion injury in rat hearts and its impact on HIF-1α and caspase-3 expression

Abstract

This study was designed to investigate possible protective effects of sevoflurane on myocardial ischemia-reperfusion injury (MIRI) and its impact on expression of HIF-1α and caspase-3 in rats, so as to provide new insights for the treatment of MIRI. Forty SD rats were randomly divided into four groups (n=10) including Sham operation (Sham), ischemia-reperfusion (IR), sevoflurane preconditioning group (Sevo-Pre) and sevoflurane post-conditioning (Sevo-Post) groups. Perfusion was performed using ex vivo heart perfusion. The baseline values of cardiac function were recorded in each group at the end of balanced perfusion and after 60 min of reperfusion. Myocardial infarct size (MIS) was calculated at the end of perfusion using TTC staining. Levels of HIF-1α and caspase-3 protein and HIF-1α (western blotting) and Bcl-2 mRNA (RT-qPCR) were detected at the end of reperfusion. Our results showed no significant differences in cardiac function between the groups at the end of the balanced perfusion. After reperfusion for 60 min, however, the cardiac functions of the Sevo-Pre and Sevo-Post groups were significantly better than those in the IR group, and the MIS at the end of reperfusion was significantly decreased. Western blotting and RT-qPCR showed that expression of HIF-1α protein was significantly increased, expression of caspase-3 protein was significantly decreased and expression of HIF-1α and Bcl-2 mRNA were significantly increased in Sevo-Pre and Sevo-Post groups compared with the levels in the IR group at the end of reperfusion. There were no significant differences in experimental results between Sevo-Pre and Sevo-Post groups. Our data support the idea that sevoflurane can improve MIRI in rats by improving cardiac function and reducing MIS. This protective effect seems to be achieved by activation of HIF-1α and inhibition of caspase-3.

Transcriptomic analysis reveals the molecular mechanism of Alzheimer‐related neuropathology induced by sevoflurane in mice

“…Sev is a volatile anesthetic widely used in clinical practice. Although the efficacy and safety of Sev across the patient populations have been demonstrated and some reports have suggested that it may also have protective effects in other organs 28,29 and a large number of studies and epidemiological investigations during the past two decades have demonstrated that general anesthesia (including exposure to Sev) could be a potential risk factor for the development of cognitive dysfunctions, such as AD and POCD, especially in old people. 7,8,[30][31][32] However, the precise molecular mechanism of cognitive dysfunction induced by Sev is still unclear.…”

Hypoxia signaling in human diseases and therapeutic targets

“…Specific adenosine receptor agonists such as neladenoson (ADORA1 agonist) or regadenoson (ADORA2A agonist) are undergoing clinical trials to better understand the effect they may have in organ protection. Interestingly, sevoflurane (fluoromethyl hexafluoroisopropyl ether), an inhalation anesthetic, which is commonly used in clinical practice, has been reported to have preconditioning effects mediated by an increase in HIF1A and a decrease in caspase-3 99 . Preconditioning by sevoflurane is currently undergoing trials for its effect on cardiac IRI protection.…”

Donor Preconditioning with Inhaled Sevoflurane Mitigates the Effects of Ischemia-Reperfusion Injury in a Swine Model of Lung Transplantation

“…Our study demonstrates that the SEV preconditioning in a pig LTx model exhibits significant protective effects against IRI by means of anti-inflammatory effects. Although in a rat in-vivo model of SEV pre- and postconditioning it has been shown that both strategies provided significant protection against myocardial IRI [ 39 ], it is possible that a preischemic conditioning approach may be more applicable to the setting of lung IRI. Indeed, from a practical point of view, we think that the feasibility of a short application of SEV in the organ donor would be more easily applicable in the clinical setting.…”