The negative chronotropic action and the time to peak effect (t(p)) of ATP and its related analogs [2-methylthio-ATP (2-MeSATP), alpha,beta-methylene-ATP (alpha,beta-mATP), and beta,gamma-methylene-ATP (beta,gamma-mATP)] as well as ADP, AMP, and adenosine were determined in anesthetized dogs. Intra-right atrium (RA) and intra-left main coronary artery (LM) ATP markedly suppressed sinus node automaticity. ATP induced a much greater response when administered into the LM than into the RA. The t(p) of ATP administered at the former site was much shorter than that at the latter site. Intra-LM adenosine had either no effect or a relatively very small effect, and its t(p) was significantly longer than that of intra-LM ATP. Bilateral cervical vagotomy either abolished or markedly attenuated the effect of intra-RA and intra-LM ATP; under these conditions, the actions of ATP and adenosine and their t(p) values became similar. The structure-function cascade of intra-LM ATP and its analogs was alpha,beta-mATP > 2-MeSATP > ATP > or = beta,gamma-mATP > ADP >> AMP = 0. The P2X-purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid markedly attenuated the negative chronotropic action of all purine nucleotides. It was concluded that 1) ATP triggers a cardiocardiac vagal depressor reflex by stimulating vagal afferent nerve terminals in the LV myocardium and 2) this action is mediated by P2X-purinoceptors.
In response to pressure on United Kingdom healthcare services due to the COVID-19 pandemic, a decision was made to pre-emptively awake-prone hypoxic patients with COVID-19 pneumonitis in a non intensive care unit (ICU) setting, with the aim of improving oxygenation and patient outcomes. This approach was trialled over 30 days from 30th March 2020, awake-proning patients for up to 15 hours a day in the first 72 hours of commencement. This case series was retrospectively analysed to characterise patients who tolerated the intensive regime (group A) versus those who ceased awake-proning early (group B). Additionally, length of stay in days was evaluated in the two groups. In total, 36 patients were proned – with an average of 2% point increase in oxygen saturations. Of these, 21 patients tolerated the intensive regime (average 1878 minutes/72 hours). Of the 15 people who ceased early (971 minutes/72 hours), only 4 were due to intolerable side effects. There were no major significant differences in baseline clinical characteristics between the two groups. Length of stay was significantly reduced in group A over group B even when adjusted for confounding of ICU stay (7.2 compared to 15.2 days p = 0.049). In conclusion awake-proning was successfully delivered in a level 1 setting, requiring the addition of 2 extra physiotherapy staff only. Further exploration is needed to explore the association of intensive regimes with reduced length of stay.
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