Esketamine accelerates emergence from isoflurane general anaesthesia by activating the paraventricular thalamus glutamatergic neurones in mice.

BACKGROUND: Delayed emergence from general anaesthesia poses a significant perioperative safety hazard. Subanaesthetic doses of ketamine not only deepen anaesthesia but also accelerate recovery from isoflurane anaesthesia; however, the mechanisms underlying this phenomenon remain elusive. Esketamine exhibits a more potent receptor affinity and fewer adverse effects than ketamine and exhibits shorter recovery times after brief periods of anaesthesia. As the paraventricular thalamus (PVT) plays a pivotal role in regulating wakefulness, we studied its role in the emergence process during combined esketamine and isoflurane anaesthesia. METHODS: The righting reflex and cortical electroencephalography were used as measures of consciousness in mice during isoflurane anaesthesia with coadministration of esketamine. The expression of c-Fos was used to determine neuronal activity changes in PVT neurones after esketamine administration. The effect of esketamine combined with isoflurane anaesthesia on PVT glutamatergic (PVTGlu) neuronal activity was monitored by fibre photometry, and chemogenetic technology was used to manipulate PVTGlu neuronal activity. RESULTS: A low dose of esketamine (5 mg kg-1) accelerated emergence from isoflurane general anaesthesia (474 [30] s vs 544 [39] s, P=0.001). Esketamine (5 mg kg-1) increased PVT c-Fos expression (508 [198] vs 258 [87], P=0.009) and enhanced the population activity of PVTGlu neurones (0.03 [1.7]% vs 6.9 [3.4]%, P=0.002) during isoflurane anaesthesia (1.9 [5.7]% vs -5.1 [5.3]%, P=0.016) and emergence (6.1 [6.2]% vs -1.1 [5.0]%, P=0.022). Chemogenetic suppression of PVTGlu neurones abolished the arousal-promoting effects of esketamine (459 [33] s vs 596 [33] s, P<0.001). CONCLUSIONS: Our results suggest that esketamine promotes recovery from isoflurane anaesthesia by activating PVTGlu neurones. This mechanism could explain the rapid arousability exhibited upon treatment with a low dose of esketamine.

Demonstration of a fully integrated superconducting receiver with a 2.7 THz quantum cascade laser.

We demonstrate for the first time the integration of a superconducting hot electron bolometer (HEB) mixer and a quantum cascade laser (QCL) on the same 4-K stage of a single cryostat, which is of particular interest for terahertz (THz) HEB/QCL integrated heterodyne receivers for practical applications. Two key issues are addressed. Firstly, a low power consumption QCL is adopted for preventing its heat dissipation from destroying the HEB's superconductivity. Secondly, a simple spherical lens located on the same 4-K stage is introduced to optimize the coupling between the HEB and the QCL, which has relatively limited output power owing to low input direct current (DC) power. Note that simulation techniques are used to design the HEB/QCL integrated heterodyne receiver to avoid the need for mechanical tuning. The integrated HEB/QCL receiver shows an uncorrected noise temperature of 1500 K at 2.7 THz, which is better than the performance of the same receiver with all the components not integrated.