Effect of esketamine vs dexmedetomidine adjunct to propofol sedation for pediatric 3Tesla magnetic resonance imaging: a randomized, double-blind, controlled trial.

BACKGROUND: Adequate sedation is essential for pediatric patients undergoing 3Tesla (T) magnetic resonance imaging (MRI). Using propofol alone is associated with patient arousing and adverse airway events. This study aimed to assess esketamine vs dexmedetomidine adjunct to propofol sedation for pediatric 3 T MRI. METHODS: In this randomized, double-blind, controlled trial, 114 pediatric patients aged between 6 months and 8 years were randomly assigned, in a 1:1 ratio, to the esketamine-propofol group or the dexmedetomidine-propofol group. Sedation was provided with esketamine or dexmedetomidine in combination with propofol titration. The primary outcome was the total dose of propofol. Secondary outcomes included propofol infusion dose, adverse events, time to emergence from sedation, and time to discharge from recovery room. RESULTS: A total of 111 patients completed this study (56 in the esketamine-propofol group and 55 in the dexmedetomidine-propofol group). All MRI procedures were successfully performed under sedation. The total median (IQR) dose of propofol was significantly lower in the esketamine-propofol group (159.8 [121.7, 245.2] µg/kg/min) than that in the dexmedetomidine-propofol group (219.3 [188.6, 314.8] µg/kg/min) (difference in medians [95% CI] = - 66.9 [- 87.8 to - 43.0] µg/kg/min, P < 0.0001). The use of esketamine resulted in a lower dose of propofol for titration (difference in medians [95% CI] = - 64.3 [- 75.9 to - 51.9] µg/kg/min), a shorter time to emergence (difference in means [95% CI] = - 9.4 [- 11.4 to - 7.4] min), and a reduced time to recovery room discharge (difference in means [95% CI] = - 10.1 [- 12.1 to - 8.2] min). In the dexmedetomidine-propofol group, 2 patients experienced upper airway obstruction and 6 patients had bradycardia. No episodes of oxygen desaturation or other adverse events were observed. CONCLUSIONS: Although both regimens provided effective sedation for pediatric 3 T MRI, the esketamine-propofol sedation reduced propofol requirement and facilitated recovery, without detection of increased adverse effects in the studied population. Trial registration Chinese Clinical Trial Registry (identifier: ChiCTR2100048477).

Dexmedetomidine Attenuates Ferroptosis-Mediated Renal Ischemia/Reperfusion Injury and Inflammation by Inhibiting ACSL4 via α2-AR.

Ischemia-reperfusion (I/R) injury is a serious clinical pathology associated with acute kidney injury (AKI). Ferroptosis is non-apoptotic cell death that is known to contribute to renal I/R injury. Dexmedetomidine (Dex) has been shown to exert anti-inflammatory and organ protective effects. This study aimed to investigate the detailed molecular mechanism of Dex protects kidneys against I/R injury through inhibiting ferroptosis. We established the I/R-induced renal injury model in mice, and OGD/R induced HEK293T cells damage in vitro. RNA-seq analysis was performed for identifying the potential therapeutic targets. RNA-seq analysis for differentially expressed genes (DEGs) reported Acyl-CoA synthetase long-chain family member 4 (ACSL4) related to ferroptosis and inflammation in I/R mice renal, which was validated in rodent renal. Liproxstatin-1, the specific small-molecule inhibitor of ferroptosis, significantly attenuated ferroptosis-mediated renal I/R injury with decreased LPO, MDA, and LDH levels, and increased GSH level. Inhibiting the activity of ACSL4 by the Rosiglitazone (ROSI) resulted in the decreased ferroptosis and inflammation, as well as reduced renal tissue damage, with decreasing LPO, MDA and LDH level, increasing GSH level, reducing COX2 and increasing GPx4 protein expression, and suppressing the TNF-α mRNA and IL-6 mRNA levels. Dex as a α2-adrenergic receptor (α2-AR) agonist performed renal protective effects against I/R-induced injury. Our results also revealed that Dex administration mitigated tissue damage, inhibited ferroptosis, and downregulated inflammation response following renal I/R injury, which were associated with the suppression of ACSL4. In addition, ACSL4 overexpression abolishes Dex-mediated protective effects on OGD/R induced ferroptosis and inflammation in HEK293T cells, and promotion of ACSL4 expression by α2-AR inhibitor significantly reversed the effects on the protective role of Dex. This present study indicated that the Dex attenuates ferroptosis-mediated renal I/R injury and inflammation by inhibiting ACSL4 via α2-AR.

Interaction between COX-2 and ER stress is involved in the apoptosis-induced myocardial ischemia/reperfusion injury.

PURPOSE: Apoptosis induced by excessive endoplasmic reticulum (ER) stress is accompanied by the occurrence and progression of myocardial ischemia/reperfusion (I/R) injury. COX-2 is also known to affect the development of I/R damage in myocardium. However, the interaction between COX-2 and ER stress in aggravating myocardial I/R lesion is not well characterized. Therefore, the purpose of our research was to explore the interaction between COX-2 and ER stress on myocardial apoptosis. METHODS: The left anterior descending (LAD) coronary artery was ligatured with a 6-0# suture for 0.5 hours and subsequently subjected to reperfusion for 3 hours to simulate myocardial I/R in mice. Oxygen glucose deprivation/reoxygenation (OGD/R) was performed on H9c2 cells to construct an in vitro model of this experiment. NS398 (COX-2 specific inhibitor) and Salubrinal (Sal, ER stress inhibitor) were administered to assess the function of COX-2 and ER stress in myocardial I/R impairment. CCK-8 assay was used to evaluate the viability of H9c2 cells under different treatment conditions. TUNEL and Hoechst staining were used to detect the occurrence of apoptosis. Infarct area/area at risk and Hematoxylin-eosin stained sections were assessed after I/R. Protein expressions of glucose-regulated protein 78 (GRP78), COX-2, phosphorylation of eukaryotic translation initiation factor 2 alpha (p-eIF2α), CCAAT/enhancer-binding protein homologous protein (CHOP), and Cleaved caspase 3 in the myocardium were examined using Western blotting. Changes in Cleaved caspase 3 expression in myocardial slices were measured by immunohistochemistry. RESULTS: Sal or NS398 partly reduced I/R-induced damage as testified by the apparent decrease in infarct size after I/R and reduced cell viability following OGD/R. Sal distinctly increased p-eIF2α, but caused decreased expression of COX-2, Cleaved caspase 3, and ER stress-associated proteins after I/R, suggesting that Sal effectively inhibited ER stress, apoptosis, and COX-2. Pretreatment with NS398 blocked I/R or OGD/R-induced upregulation of COX-2, Cleaved caspase 3, and ER stress-related marker proteins. CONCLUSIONS: Interaction of COX-2 and ER stress regulates apoptosis and contributes to Myocardial lesion induced by I/R.