AimsWe investigated the role of src family kinases (srcFK) in agonist-mediated Ca2+-sensitization in pulmonary artery and whether this involves interaction with the rho/rho-kinase pathway.Methods and resultsIntra-pulmonary arteries (IPAs) and cultured pulmonary artery smooth muscle cells (PASMC) were obtained from rat. Expression of srcFK was determined at the mRNA and protein levels. Ca2+-sensitization was induced by prostaglandin F2α (PGF2α) in α-toxin-permeabilized IPAs. Phosphorylation of the regulatory subunit of myosin phosphatase (MYPT-1) and of myosin light-chain-20 (MLC20) and translocation of rho-kinase in response to PGF2α were also determined. Nine srcFK were expressed at the mRNA level, including src, fyn, and yes, and PGF2α enhanced phosphorylation of three srcFK proteins at tyr-416. In α-toxin-permeabilized IPAs, PGF2α enhanced the Ca2+-induced contraction (pCa 6.9) approximately three-fold. This enhancement was inhibited by the srcFK blockers SU6656 and PP2 and by the rho-kinase inhibitor Y27632. Y27632, but not SU6656 or PP2, also inhibited the underlying pCa 6.9 contraction. PGF2α enhanced phosphorylation of MYPT-1 at thr-697 and thr-855 and of MLC20 at ser-19. This enhancement, but not the underlying basal phosphorylation, was inhibited by SU6656. Y27632 suppressed both basal and PGF2α-mediated phosphorylation. The effects of SU6656 and Y27632, on both contraction and MYPT-1 and MLC20 phosphorylation, were not additive. PGF2α triggered translocation of rho-kinase in PASMC, and this was inhibited by SU6656.Conclusions
srcFK are activated by PGF2α in the rat pulmonary artery and may contribute to Ca2+-sensitization and contraction via rho-kinase translocation and phosphorylation of MYPT-1.
Purpose Because of the anticipated surge in cases requiring intensive care unit admission, the high aerosolgenerating risk of tracheal intubation, and the specific requirements in coronavirus disease (COVID-19) patients, a dedicated Mobile Endotracheal Rapid Intubation Team (MERIT) was formed to ensure that a highly skilled team would be deployed to manage the airways of this cohort of patients. Here, we report our intubation team experience and activity as well as patient outcomes during the COVID-19 pandemic. Methods The MERIT members followed a protocolized early tracheal intubation model. Over a seven-week period during the peak of the pandemic, prospective data were collected on MERIT activity, COVID-19 symptoms or diagnosis in the team members, and demographic, procedural, and clinical outcomes of patients. Results We analyzed data from 150 primary tracheal intubation episodes, with 101 (67.3%) of those occurring in men, and with a mean (standard deviation) age of 55.7 (13.8) yr. Black, Asian, and minority ethnic groups accounted for 55.7% of patients. 91.3% of tracheal intubations were performed with videolaryngoscopy, and the first pass success rate was 88.0%. The 30-day survival was 69.2%, and the median [interquartile range] length of critical care stay was 11 [6-20] days and of hospital stay was 12 [7-22] days. Seven (11.1%) MERIT healthcare professionals self-isolated because of COVID-19 symptoms, with a total 41 days of clinical work lost. There was one reported incident of a breach of personal protective equipment and multiple anecdotal reports of doffing breaches. Conclusion We have shown that a highly skilled designated intubation team, following a protocolized, early tracheal intubation model may be beneficial in improving patient and staff safety, and could be considered by other institutions in future pandemic surges.
A transgender female patient, who had previously undergone gender-confirming feminisation surgery to the face and larynx, was scheduled for thoracic surgery requiring one-lung ventilation. We encountered unexpected difficult airway management and difficulty inserting an appropriately-sized double-lumen tube. A size 41Fr double-lumen tube, which is selected commonly for biological males, was used eventually for lung isolation and subsequently exchanged for a size 6.5 single-lumen tracheal tube at the end of the case, before successful extubation with a staged extubation set. It is important to highlight the challenges faced, as the care of transgender patients is likely to be unfamiliar to most anaesthetists, despite the increase in the number of gender-confirming procedures performed. Many of these procedures involve the face and airway and can result in significant challenges for airway management, including appropriate sizing of tracheal tubes and their correct placement. It is also possible that patients may not volunteer a history of these procedures and it should be enquired about specifically as part of the anaesthetic pre-assessment.
The authors present a case report of a previously healthy 15-year-old male who experienced global weakness in the presence of profound hypokalaemia following a high-voltage electrical arc injury. The clinical picture is discussed in the context of our evolving understanding of electrical injuries and potassium homeostasis.
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