The Association Between Ventilatory Ratio and Mortality of Adult Patients with ARDS: Systematic Review and Meta-Analysis

Background: Ventilatory ratio is a simple bedside index of impaired efficiency of ventilation and correlates well with physiological dead space fraction in patients with ARDS. So it was regarded as a dead-space marker associated with mortality in mechanically ventilated adults with ARDS. However, the association between VR and outcome of patients with ARDS remains largely unknown. Methods: We searched articles in three electronic databases including PubMed, EMBASE and Web of Science. All the English publications up to 1 st Oct. 2021 will be searched without any restriction of countries. All the observational study that investigated the association between ventilatory ratio and the mortality of ARDS patients were identified in this meta-analysis. The main outcome was mortality. Summary estimates of effect using odds ratio (OR) for dichotomous outcomes with accompanying 95% confidence interval (CI) were expressed. Results: A total of 9 trials enrolling 5638 patients were finally included in this meta-analysis. The results revealed that the use of ventilatory ratio could be significantly related to the mortality in adult ARDS (OR=1.27; 95% CI 1.10 to 1.47; P=0.001). Ventilatory ratio may have the capability of predicting the mortality of NON- COVID-related patients (OR 1.39, 95% CI 1.12 to 1.73 P = 0.003) while it has no predictable significance in patients with COVID (OR 1.18, 95% CI 0.94 to 1.48 P = 0.16). Importantly, the dynamic changes of VR adds more predictable value (OR 1.21 vs 1.19). Conclusion: Our study suggests that ventilatory ratio can be regarded as a valuable marker to predict the mortality of adult patients with ARDS. Compared to patients with COVID, ventilatory ratio is more predictable in patients with NON-COVID. What’s more, the dynamic changes of VR may have the potential to improve the prognostic value.

Transepithelial flux of early and advanced glycation compounds across Caco-2 cell monolayers and their interaction with intestinal amino acid and peptide transport systems

Maillard products arise from condensation reactions between amino acids or proteins with reducing sugars during food processing. As ubiquitous components of human food, these early or advanced glycation products may be subject to intestinal absorption. The present study was performed to investigate the intestinal uptake of Maillard products and to determine whether they are substrates for peptide and amino acid transporters expressed at the apical membrane of Caco-2 cells. At a concentration of 10mm, Nɛ-(carboxymethyl)-L-lysine, Nα-hippuryl-Nɛ-(1-deoxy-d-fructosyl)-l-lysine,Nα-hippuryl-Nɛ-(carboxymethyl)-L-lysine and Nɛ-(1-deoxy-d-fructosyl)-l-lysine inhibited the [14C]glycylsarcosine uptake mediated by the H+–peptide co-transporter PEPT1 by 13 to 45%.For Nɛ-(1-deoxy-d-fructosyl)-l-lysine, an inhibitory constant of 8·7mm was determined, reflecting a low affinity to PEPT1 in comparison with natural dipeptides. Uptake of l-[3H]lysine was weakly affected by Nɛ-(carboxymethyl)-L-lysine, Nα-hippuryl-l-lysine and Nα-hippuryl-Nɛ-(carboxymethyl)-L-lysine but strongly inhibited by Nɛ-(1-deoxy-d-fructosyl)-l-lysine (81%). None of the Maillard products was able to inhibit the uptake of l-[3H]leucine by more than 15%. We also studied the transepithelial flux of Maillard productsacross Caco-2 cell monolayers cultured on permeable filters. The flux rates of Maillard products ranged from 0·01 to 0·3%/cm2 per h and were shown to be muchlower than those of carrier substrates such as glycylsarcosine, l-proline and the space marker 14C]mannitol. We conclude that the Maillard products investigated in the present study are neither transported by PEPT1 nor by carriers for neutral amino acids. The low transepithelial flux measured for these compounds most probably occurs by simple diffusion.

Basolateral transport of taurine in epithelial cells of isolated, perfused Mytilus californianus gills.

We found that the basolateral surface of the gill epithelium of the marine mussel Mytilus californianus possesses a carrier-mediated process capable of concentrating taurine within epithelial cells. We used retrograde perfusion of gill sections to demonstrate the kinetics, specificity and ion-dependence of taurine transport. [3H]taurine was concentrated relative to a space marker ([14C]mannitol); this accumulation was blocked by the inclusion of 10 mmol l-1 unlabeled taurine in the perfusate. The drop in [3H]taurine uptake at increasing concentrations of unlabeled taurine was fitted to Michaelis-Menten kinetics and indicated a basolateral process with a taurine concentration at which transport is half-maximal (Kt) of 35.3 mumol l-1 and a maximal flux (Jmax) of 0.35 mumol g-1 wet mass h-1. Taurine accumulation on the apical surface had a higher affinity (Kt = 9.5 mumol l-1) and a higher maximum rate of transport (Jmax = 1.23 mumol g-1 h-1). Basolateral transport was inhibited by inclusion in the perfusate of 1 mmol l-1 of another beta-amino acid (beta-alanine), but not by inclusion of alpha-alanine, glutamic acid or betaine. The dependence of basolateral taurine transport on Na+ (when replaced with N-methyl-D-glucamine) was sigmoidal with an apparent Hill coefficient of 2.3, indicating that more than one Na+ is necessary for the transport of each taurine molecule. Complete substitution of Cl- in bathing media reduced taurine accumulation by 90% and 70% on the apical and basolateral surfaces, respectively. Taurine accumulation on both surfaces was reduced by only 20% when Cl- was reduced from 496 to 73 mmol l-1, suggesting that taurine uptake is not significantly influenced by the changes in Cl- concentration accompanying the salinity fluctuations normally encountered by mussels. We estimate that the various Na+ and Cl- gradients naturally encountered by epithelial cells are capable of providing ample energy to maintain a high intracellular concentration of taurine. We suggest that the ability of epithelial cells to accumulate taurine across the basolateral surface from the hemolymph plays a significant role in the intracellular regulation of this important osmolyte and may effect osmolality-dependent changes in the intracellular concentration of taurine.

Light-dependent hydration of the space surrounding photoreceptors in the cat retina

We have studied the effect of retinal illumination on the concentration of the extracellular space marker tetramethylammonium (TMA+) in the dark-adapted cat retina using double-barreled ion-selective microelectrodes. The retina was loaded with TMA+ by a single intravitreal injection. Retinal illumination produced a slow decrease in , which was maximal in amplitude in the most distal portion of the space surrounding photoreceptors, the subretinal space. The light-evoked decrease in was considerably slower and of a different overall time course than the light-evoked decrease in , also recorded in the subretinal space. decreased to a peak at 38 s after the onset of illumination, then slowly recovered towards the baseline, and transiently increased following the offset of illumination. It resembled the light-evoked decreases previously recorded in the in vitro preparations of frog (Huang & Karwoski, 1990, 1992) and chick (Li et al., 1992, 1994) but was considerably larger in amplitude, 22% compared with 7%. As in frog, where it was first recorded, the light-evoked decrease is considered to originate from a light-evoked increase in the volume of the subretinal space (or subretinal hydration). A mathematical model accounting for diffusion predicted that the volume increase underlying the response was 63% on average and could be as large as 95% and last for minutes. The estimated volume increase was then used to examine its effect on K+ concentration in the subretinal space. We conclude that a light-dependent hydration of the subretinal space represents a significant physiological event in the intact cat eye, which should affect the organization of the interphotoreceptor matrix, and the concentrations of all ions and metabolites located in the subretinal space.

Origins of endogenous noradrenaline overflow during reperfusion of the ischaemic rat heart

1. Reperfusion of the globally ischaemic isolated rat heart is associated with an enhanced overflow of endogenous noradrenaline (NA) after ischaemic periods of 20, 40 or 60 min but not of 10 min. 2. Reperfusion NA overflow, after 40 min of ischaemia, is suppressed by desipramine and increased when ischaemia follows a period of substrate deprivation. 3. Reperfusion after 40 min of ischaemia is associated with a significant rise in NA concentration despite a simultaneous 20-fold increase in flow. This increase in concentration is abolished by treatment with desipramine or if ischaemia follows a period of substrate deprivation. 4. Reperfusion NA overflow correlates with the reperfusion overflow of an extracellular space marker infused before the ischaemic episode. 5. These results suggest that ischaemia is heterogeneous and that NA is released into regions of particularly profound ischaemia from which it is subsequently eluted during reperfusion.