Dexmedetomidine improves cardiac function and protects against maladaptive remodeling following myocardial infarction

Abstract

Dexmedetomidine (DEX), a highly specific and selective α2 adrenergic receptor agonist, has been demonstrated to possess potential cardioprotective effects. However, the mechanisms underlying this process remain to be fully illuminated. In the present study, a myocardial infarction (MI) animal model was generated by permanently ligating the left anterior descending coronary artery in mice. Cardiac function and collagen content were evaluated by transthoracic echocardiography and picrosirius red staining, respectively. Apoptosis was determined by the relative expression levels of Bax and Bcl-2 and the myocardial caspase-3 activity. Additionally, nicotinamide adenine dinucleotide phosphate oxidase (NOX)-derived oxidative stress was evaluated by the relative expression of Nox2 and Nox4, along with the myocardial contents of malondialdehyde (MDA) and superoxide dismutase (SOD) activity. It was demonstrated that intraperitoneal DEX treatment (20 µg/kg/day) improved the systolic function of the left ventricle, and decreased the fibrotic changes in post-myocardial infarction mice, which was paralleled by a decrease in the levels of apoptosis. Subsequent experiments indicated that the restoration of redox signaling was achieved by DEX administration, and the over-activation of NOXs, including Nox2 and Nox4, was markedly inhibited. In conclusion, this present study suggested that DEX was cardioprotective and limited the excess production of NOX-derived ROS in ischemic heart disease, implying that DEX is a promising novel drug, especially for patients who have suffered MI.

Brown adipose tissue-derived FGF21 mediates the cardioprotection of dexmedetomidine in myocardial ischemia/reperfusion injury

“…To investigate the cardioprotective effects of DEX against MI/RI, we established a mouse model of MI/RI to assess cardiac function and infarct sizes. Consistent with previous reports [33], the DEX-administered group exhibited preserved left ventricular systolic function compared to the vehicle-treated group subjected to MI/RI, as monitored by cardiac ultrasound (Fig. 1A-B).…”

“…Besides, other studies have revealed that DEX preconditioning protects the hearts against I/R injury via alleviating myocardial in ammation and apoptosis [41], downregulation of the endoplasmic reticulum stress signaling pathway [42],or exerting antioxidant stress through the activation of the Keap1/Nrf2/ARE signal pathway [43]. In particular, DEX pretreatment prevents maladaptive remodeling from myocardial infarction [33].…”

PAGln, an Atrial Fibrillation-Linked Gut Microbial Metabolite, Acts as a Promoter of Atrial Myocyte Injury

“…Next, we evaluated the effect of PAGln on atrial myocytes. Compared with the control group, PAGln (100 μM, 24 h) intervention significantly increased ROS generation (1.44 ± 0.18 vs. 0.80 ± 0.17 fold change; p = 0.011), NOX activity, a major source of excess ROS in the cardiovascular system [ 24 ], and apoptosis (56.25 ± 1.18 vs. 49.76 ± 0.93%, p = 0.002) in mouse HL-1 cells ( Figure 4 A–C). Moreover, treating HL-1 cells with PAGln for 24 h induced a striking decrease in SOD activity, a myocardial endogenous antioxidant [ 24 ], and the MTT values ( Figure 4 D,E), showing that PAGln could dramatically impair atrial myocyte viability.…”

Dexmedetomidine combined with propofol attenuates myocardial ischemia/reperfusion injury by activating the AMPK signaling pathway

“…AST, CK-MB, cTnl, and LDH are common factors that can reflect myocardial function damage. Dex and PPF are known to have cardioprotective effects according to previous research[ 36 , 41 ]. In the present study, Dex or/and PPF down-regulated the levels of cTnl, CK-MB, AST, and LDH, especially Dex combined with PPF.…”