Sevoflurane post-conditioning reduces rat myocardial ischemia reperfusion injury through an increase in NOS and a decrease in phopshorylated NHE1 levels

Abstract

The protective effects of sevoflurane post-conditioning against myocardial ischemia/reperfusion (I/R) injury (MIRI) have been previously reported. However, the mechanisms responsible for these protective effects remain elusive. In this study, in order to investigate the molecular mechanisms responsible for the protective effects of sevoflurane post-conditioning on isolated rat hearts subjected to MIRI, Sprague-Dawley rat hearts were randomly divided into the following 6 groups: i) the sham-operated control; ii) 2.5% sevoflurane; iii) ischemia/reperfusion (I/R); iv) 2.5% sevoflurane post-conditioning plus I/R; v) 2.5% sevoflurane post-conditioning + NG-nitro-L-arginine methyl ester (L-NAME) plus I/R; and vi) L-NAME plus I/R. The infarct size was measured using 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Additionally, the myocardial nitric oxide (NO), NO synthase (NOS) and nicotinamide adenine dinucleotide (NAD+) levels were determined. Autophagosomes and apoptosomes in the myocardium were detected by transmission electron microscopy. The levels of Bcl-2, cleaved caspase-3, Beclin-1, microtubule-associated protein light chain 3 (LC3)-I/II, Na+/H+ exchanger 1 (NHE1) and phosphorylated NHE1 protein were measured by western blot analysis. NHE1 mRNA levels were measured by reverse transcription-quantitative polymerase chain reaction. Compared with the I/R group, 15 min of exposure to 2.5% sevoflurane during early reperfusion significantly decreased the myocardial infarct size, the autophagic vacuole numbers, the NHE1 mRNA and protein expression of cleaved caspase-3, Beclin-1 and LC3-I/II. Post-conditioning with 2.5% sevoflurane also increased the NO and NOS levels and Bcl-2 protein expression (P<0.05 or P<0.01). Notably, the cardioprotective effects of sevoflurane were partly abolished by the NOS inhibitor, L-NAME. The findings of the present study suggest that sevoflurane post-conditioning protects the myocardium against I/R injury and reduces the myocardial infarct size. The underlying protective mechanisms are associated with the inhibition of mitochondrial permeability transition pore opening, and with the attenuation of cardiomyoctye apoptosis and excessive autophagy. These effects are mediated through an increase in NOS and a decrease in phopshorylated NHE1 levels.

Suppression of Long Non-Coding RNA LINC00652 Restores Sevoflurane-Induced Cardioprotection Against Myocardial Ischemia-Reperfusion Injury by Targeting GLP-1R Through the cAMP/PKA Pathway in Mice

“…Previous studies showed that sevoflurane could completely prevent the neuronal eosinophilic damage of the brain in incomplete cerebral ischemia and improve neurological outcomes after severe cerebral ischemia in rats compared with animals anesthetized with Zoletil [29,30]. A previous study conducted by Cao et al demonstrated that sevoflurane post-conditioning could significantly attenuate myocardial I/R injury and inhibit cardiac cell apoptosis and excessive autophagy [31]. However, compared with the Sevo + I/R group, the LVEF and LVFS of the si-LINC00652 + Sevo + I/R group increased, whereas the LVEF and LVFS of the mice in the H89 + Sevo + I/R group decreased and returned to the level of the I/R group compared with the Sevo + I/R group, suggesting that interfering with the expression of LINC00652 could alleviate the degree of myocardial I/R injury, while inhibiting the cAMP/PKA signaling pathway could strengthen the degree of myocardial I/R injury in mice.…”

Deferoxamine-activated hypoxia-inducible factor-1 restores cardioprotective effects of sevoflurane postconditioning in diabetic rats

“…Sevoflurane, a commonly used inhalation anaesthetic agent in clinical practice, is considered the cornerstone of this drug class because of its favourable characteristics, including smooth induction of anaesthesia, rapid post-operative recovery and minimal impact on hemodynamics. Several studies have demonstrated that SpostC can protect healthy myocardium from I/R injury, [6][7][8][9]28 but the underlying mechanism remains unclear. Interestingly, our previous studies found that the protective effects of SpostC on isolated myocardial mitochondria can be attributed to the upregulation of HIF-1a.…”

“…5 Sevoflurane is an ideal inhaled anaesthetic agent that is widely used in peri-operative anaesthesia. [6][7][8][9] Unfortunately, diabetes abolishes the cardioprotective effects of SpostC, [10][11][12] and the underlying mechanism remains unclear. [6][7][8][9] Unfortunately, diabetes abolishes the cardioprotective effects of SpostC, [10][11][12] and the underlying mechanism remains unclear.…”

“…On normal myocardium, sevoflurane postconditioning (SpostC) has cardioprotective effects that are similar to ischaemic preconditioning, and SpostC is a potentially important approach for the prevention of perioperative cardiac ischaemia/reperfusion (I/R) injury. [6][7][8][9] Unfortunately, diabetes abolishes the cardioprotective effects of SpostC, [10][11][12] and the underlying mechanism remains unclear. Therefore, it is of great significance to improve or restore SpostC cardioprotection under diabetic conditions and thereby reduce the incidence of adverse peri-operative cardiac events.…”

Sevoflurane ameliorates doxorubicin-induced myocardial injury by affecting the phosphorylation states of proteins in PI3K/Akt/mTOR signaling pathway

“…Akt signaling pathway plays an important role in cardiac growth, contractile function, and coronary angiogenesis [3]. A previous study demonstrated that sevoflurane reduced DOX-induced rat cardiac injury [4]. Thus, sevoflurane improves DOX-induced cardiac injury perhaps by affecting Akt signaling pathway.…”