Dexmedetomidine – ABC CARDIOL

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Editorial

Pharmacological Conditioning is Salvageable by Dexmedetomidine: How a Sedative Can Mitigate I/R Injuries?

Acute myocardial infarction (AMI) is a severe condition affecting millions worldwide.During AMI, the blood supply to the heart muscle is interrupted, reducing the availability of nutrients and oxygen. Restoring blood flow is essential to save the heart muscle; paradoxically, reperfusion is not an entirely benign mechanism, and it induces reperfusion injuries.Therefore, treatments to mitigate ischemia-reperfusion (I/R) injuries are necessary. So far, there are no entirely effective pharmacological treatments to relieve I/R injuries in patients under AMI. However, pharmacological conditioning with Dexmedetomidine, a medication primarily used as a sedative and analgesic, has been reported as a promising cardioprotective agent against I/R injuries.

Due to its sedative and analgesic effects, Dexmedetomidine is a selective agonist of the alpha-2 adrenergic receptor (α2-AR) commonly used in hospitals, especially in intensive care units and surgery rooms. Although its association with cardiac protection has been suggested in previous studies,^–the work of Chen et al.,the topic of this short editorial, delved into understanding Dexmedetomidine’s underlying mechanism of cardioprotection. Thus, in addition to demonstrating that pharmacological preconditioning with Dexmedetomidine improves cardiac function and reduces the myocardial infarct area after I/R, one of the most significant findings of this study was the relationship between Dexmedetomidine and mitophagy.

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Original Article

Dexmedetomidine Preconditioning Attenuates Myocardial Ischemia/Reperfusion Injury in Rats by Suppressing Mitophagy Via Activating Α2-Adrenergic Receptor

YaHua Chen et al. Hui Chen YuJiao Chen ZaiQun Yang … Tao Zhou Wei Xu

Abstract

Background

Dexmedetomidine (DEX), a specific α2-adrenergic receptor agonist, is protective against myocardial ischemia/reperfusion injury (MIRI). However, the association between DEX preconditioning-induced cardioprotection and mitophagy suppression remains unclear.

Objective

Hence, we aimed to investigate whether DEX preconditioning alleviates MIRI by suppressing mitophagy via α2-adrenergic receptor activation.

Method

Sixty isolated rat hearts were treated with or without DEX before inducing ischemia and reperfusion; an α2-adrenergic receptor antagonist, yohimbine (YOH), was also administered before ischemia, alone or with DEX. The heart rate (HR), left ventricular diastolic pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), maximal and minimal rate of left ventricular pressure development (±dp/dtmax), and myocardial infarction size were measured. The mitochondrial ultrastructure and autophagosomes were assessed using transmission electron microscopy. Mitochondrial membrane potential and reactive oxygen species (ROS) levels were measured using JC-1 and dichloride hydrofluorescein diacetate assays, respectively. The expression levels of the mitophagy-associated proteins Beclin1, LC3II/I ratio, p62, PINK1, and Parkin were detected by western blotting.

Results

Compared with the control group, in the ischemia/reperfusion group, the HR, LVDP, and ±dp/dtmax were remarkably decreased (p< 0.05), whereas LVEDP and infarct sizes were significantly increased (p< 0.05). DEX preconditioning significantly improved cardiac dysfunction reduced myocardial infarction size, maintained mitochondrial structural integrity, increased mitochondrial membrane potential, inhibited autophagosomes formation, and decreased ROS production and Beclin1, LC3II/I ratio, PINK1, Parkin, and p62 expression(p< 0.05). When DEX and YOH were combined, YOH canceled the effect of DEX, whereas the use of YOH alone had no effect.

Conclusion

Therefore, DEX preconditioning was cardioprotective against MIRI in rats by suppressing mitophagy via α2-adrenergic receptor activation.

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Original Article

Dexmedetomidine Preconditioning Reduces Myocardial Ischemia-Reperfusion Injury in Rats by Inhibiting the PERK Pathway

YuJiao Chen et al. Song Cao Hui Chen CunZhi Yin … XinPeng Xu ZaiQun Yang

Abstract

Background

Ischemic heart disease has attracted much attention due to its high mortality rates, treatment costs and the increasing morbidity in the young population. Strategies for reperfusion have reduced mortality. However, reperfusion can lead to cardiomyocyte death and subsequent irreversible myocardial damage. At present, the timely and targeted treatment of ischemia-reperfusion (I/R) injury is often lacking.

Objectives

To evaluate if dexmedetomidine (DEX) has a protective effect in myocardiual I/R and explore the possible mechanism behind it.

Methods

Rat hearts were perfused with a Langendorff perfusion system, and randomly assigned to five groups: control group, perfused with Krebs-Henseleit (K-H) solution for 205 minutes without ischemia; and four test groups that underwent 40 minutes of global ischemia and 120 min of reperfusion. The DEX group, the yohimbine (YOH) group and the DEX + YOH group were perfused with DEX (10 nM), YOH (1 μM) or the combination of DEX and YOH prior to reperfusion, respectively. Cardiac hemodynamics, myocardial infarct size, and myocardial histology were evaluated. The expression of glucose-related protein 78 (GRP78), protein kinase R-like ER kinase (PERK), phosphorylated PERK, eukaryotic initiation factor 2α (eIF2α), phosphorylated eIF2α, activating transcription factor 4 (ATF4), and CCAAT/enhancer-binding protein homologous protein (CHOP) were assessed. P<0.05 was considered to indicate a statistically significant difference.

Results

DEX preconditioning improved the cardiac function of I/R hearts, reduced myocardial infarction, myocardial apoptosis, and the expression of GRP78, p-PERK, eIF2α, p-eIF2α, ATF4 and CHOP.

Conclusions

DEX pretreatment reduced myocardial I/R injury by suppressing apoptosis, which was induced by the PERK pathway.

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Pharmacological Conditioning is Salvageable by Dexmedetomidine: How a Sedative Can Mitigate I/R Injuries?

Dexmedetomidine Preconditioning Attenuates Myocardial Ischemia/Reperfusion Injury in Rats by Suppressing Mitophagy Via Activating Α2-Adrenergic Receptor

Abstract

Background

Objective

Method

Results

Conclusion

Dexmedetomidine Preconditioning Reduces Myocardial Ischemia-Reperfusion Injury in Rats by Inhibiting the PERK Pathway

Abstract

Background

Objectives

Methods

Results

Conclusions

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