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Ischemic cardiac injury can be substantially alleviated by exposing the heart to pharmacological agents such as volatile anesthetics before occurrence of ischemia-reperfusion. A hallmark of this preconditioning phenomenon is its memory, when cardioprotective effects persist even after removal of preconditioning stimulus. Since numerous studies pinpoint mitochondria as crucial players in protective pathways of preconditioning, the aim of this study was to investigate the effects of preconditioning agent isoflurane on the mitochondrial bioenergetic phenotype. Endogenous flavoprotein fluorescence, an indicator of mitochondrial redox state, was elevated to 195 [+ or -] 16% of baseline upon isoflurane application in intact cardiomyocytes, indicating more oxidized state of mitochondria. Isoflurane treatment also elicited partial dissipation of mitochondrial transmembrane potential, which remained depolarized even after anesthetic withdrawal (tetramethyl-rhodamine fluorescence intensity declined to 83 [+ or -] 3 and 81 [+ or -] 7% of baseline during isoflurane exposure and washout, respectively). Mild uncoupling, with preserved ATP synthesis, was also detected in mitochondria that were isolated from animals that had been previously preconditioned by isoflurane in vivo, revealing its memory nature. These mitochondria, after exposure to hypoxia and reoxygenation, exhibited better preserved respiration and ATP synthesis compared with mitochondria from nonpreconditioned animals. Partial mitochondrial depolarization was paralleled by a diminished [Ca.sup.2+] uptake into isoflurane-treated mitochondria, as indicated by the reduced increment in rhod-2 fluorescence when mitochondria were challenged with increased [Ca.sup.2+] (180 [+ or -] 24 vs. 258 [+ or -] 14% for the control). In conclusion, isoflurane preconditioning elicits partial mitochondrial uncoupling and reduces mitochondrial [Ca.sup.2+] uptake. These effects are likely to reduce the extent of the mitochondrial damage after the hypoxic stress. cardioprotection; uncoupling doi: 10.1152/ajpcell.00221.2006.

Biallelic missense mutations in the nuclear-encoded, cytosolic isoleucyl-tRNA synthetase (IARS) gene are associated with a rare and complex multisystemic phenotype, including growth retardation, intellectual disability, muscular hypotonia, diabetes mellitus, and deafness. These mutations impact the cytosolic isoform of IARS, which plays a crucial role in protein synthesis. The pathogenesis involves mitochondrial dysfunction, despite IARS being primarily a cytosolic enzyme, potentially linking it to the observed clinical manifestations. The efficacy of cochlear implantation for deafness due to IARS mutations and the safety of general anesthesia in such patients remain unclear. This report describes a rare case of progressive sensorineural hearing loss caused by IARS mutation-associated mitochondrial disease, which was successfully treated with cochlear implantation. Additionally, we discuss the safety of general anesthesia in this patient. A Japanese woman with IARS mutation-associated mitochondrial disease was diagnosed with severe bilateral sensorineural hearing loss at five years of age and immediately received hearing aids. Her hearing progressively deteriorated to profound impairment, necessitating cochlear implantation at 26 years of age, which resulted in satisfactory hearing. Furthermore, no perioperative general anesthesia-related adverse events were reported. Our case demonstrates that cochlear implantation can effectively restore hearing. This suggests that sensorineural hearing loss caused by IARS deficiency is primarily due to cochlear dysfunction. This case demonstrated that hearing loss is a crucial feature of IARS mutation-associated mitochondrial disease, which can be mitigated by cochlear implantation. While general anesthesia can be safely administered, careful consideration of anesthetic choices, such as avoiding depolarizing muscle relaxants and prolonged use of propofol, is essential to prevent complications. In this case, general anesthesia was well tolerated without perioperative events, providing valuable insight into the potential safety of such procedures in similar patients. Nevertheless, further studies are needed to confirm these findings across a broader population., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board Affiliated with Jikei University School of Medicine issued approval 34-232[11383]). The Ethics Committee has reviewed the above application and hereby notifies that it has been approved. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Motegi et al.)

Esmolol and landiolol are ultra-short-acting intravenous beta-blockers. Both drugs have high cardioselectivity (beta1/beta2 selectivity of esmolol : 33, landiolol: 255) and short elimination half time (esmolol : 9 min, landiolol : 4 min). Since the duration of beta-adrenergic blockade is short and cardioselectivity is high compared with traditional intravenous beta-blocker propranolol, both drugs are titrated easily. Its use is particularly suited to critically ill patient and for perioperative period. In clinical settings, both drugs have been used for prevention of perioperative tachycardia after endotracheal intubation or surgical incision and treatment of supuraventricular arrhythmias. Esmolol also has been used for treatment of perioperative hypertension and for reducing cardiac work in patients with ischemic heart disease. Recently, it was reported that prophylactic administration of esmolol may prevent perioperative myocardial ischemia in high risk group. Landiolol is a newer drug compared with esmolol. There are not many clinical trials on landiolol. However, since landiolol has higher cardioselectivity and tends to have less cardiodepressant effect than esmolol, clinical indication of landiolol may be extended. Additional data from large studies are required to evaluate the clinical efficacy and safety of landiolol for a variety of diseases.