BackgroundVascular congestion of the renal medulla—trapped red blood cells in the medullary microvasculature—is a hallmark finding at autopsy in patients with ischemic acute tubular necrosis. Despite this, the pathogenesis of vascular congestion is not well defined.MethodsIn this study, to investigate the pathogenesis of vascular congestion and its role in promoting renal injury, we assessed renal vascular congestion and tubular injury after ischemia reperfusion in rats pretreated with low-dose LPS or saline (control). We used laser Doppler flowmetry to determine whether pretreatment with low-dose LPS prevented vascular congestion by altering renal hemodynamics during reperfusion.ResultsWe found that vascular congestion originated during the ischemic period in the renal venous circulation. In control animals, the return of blood flow was followed by the development of congestion in the capillary plexus of the outer medulla and severe tubular injury early in reperfusion. Laser Doppler flowmetry indicated that blood flow returned rapidly to the medulla, several minutes before recovery of full cortical perfusion. In contrast, LPS pretreatment prevented both the formation of medullary congestion and its associated tubular injury. Laser Doppler flowmetry in LPS-pretreated rats suggested that limiting early reperfusion of the medulla facilitated this protective effect, because it allowed cortical perfusion to recover and clear congestion from the large cortical veins, which also drain the medulla.ConclusionsBlockage of the renal venous vessels and a mismatch in the timing of cortical and medullary reperfusion results in congestion of the outer medulla’s capillary plexus and promotes early tubular injury after renal ischemia. These findings indicate that hemodynamics during reperfusion contribute to the renal medulla’s susceptibility to ischemic injury.

We tested the hypothesis that oral NaHCO intake stimulates splenic anti-inflammatory pathways. Following oral NaHCO loading, macrophage polarization was shifted from predominantly M1 (inflammatory) to M2 (regulatory) phenotypes, and FOXP3CD4 T-lymphocytes increased in the spleen, blood, and kidneys of rats. Similar anti-inflammatory changes in macrophage polarization were observed in the blood of human subjects following NaHCO ingestion. Surprisingly, we found that gentle manipulation to visualize the spleen at midline during surgical laparotomy (sham splenectomy) was sufficient to abolish the response in rats and resulted in hypertrophy/hyperplasia of the capsular mesothelial cells. Thin collagenous connections lined by mesothelial cells were found to connect to the capsular mesothelium. Mesothelial cells in these connections stained positive for the pan-neuronal marker PGP9.5 and acetylcholine esterase and contained many ultrastructural elements, which visually resembled neuronal structures. Both disruption of the fragile mesothelial connections or transection of the vagal nerves resulted in the loss of capsular mesothelial acetylcholine esterase staining and reduced splenic mass. Our data indicate that oral NaHCO activates a splenic anti-inflammatory pathway and provides evidence that the signals that mediate this response are transmitted to the spleen via a novel neuronal-like function of mesothelial cells.

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Background: Monitoring blood glucose concentrations is common in critically ill neonatal foals, especially septic foals and those receiving naso-esophageal feedings or IV parenteral nutrition. Glucose typically is measured using a point-of-care (POC) glucometer but requires repeated restraint and blood collections, which may cause irritation at venipuncture sites and increased demands on nursing staff. Continuous glucose monitoring systems (CGMS) may provide an accurate alternative for monitoring blood glucose concentration.Objectives: To determine the correlation and accuracy of a CGMS to monitor neonatal foals' blood glucose concentrations as compared to a POC glucometer and laboratory chemistry analysis (CHEM).Animals: Samples from 4 healthy and 4 ill neonatal foals.Methods: A CGMS was placed on each foal, and glucose measurements acquired from this device were compared to simultaneous measurements of blood glucose concentration using a POC glucometer and CHEM.Results: Two-hundred matched glucose measurements were collected from 8 neonatal foals. The mean bias (95% limits of agreement) between CGMS and CHEM, CGMS and POC glucometer, and POC glucometer and CHEM was 3.97 mg/dL (À32.5 to 40.4), 18.2 mg/dL (À28.8 to 65.2), and 22.18 mg/dL (À9.3 to 53.67), respectively. The Pearson's correlation coefficient (r) was significantly correlated among all devices: GCMS and CHEM (r = 0.81), CGMS and POC glucometer (r = 0.77) and POC glucometer-CHEM (r = 0.92).Conclusions and Clinical Importance: Within the blood glucose concentration ranges in this study (78-212 mg/dL), CGMS measurements were significantly correlated with CHEM, suggesting that it is an acceptable method to provide meaningful, immediate, and continuous glucose concentration measurements in neonatal foals while eliminating the need for repeated restraint and blood collection.

We tested the hypothesis that ‘Oral NaHCO3 intake stimulates splenic anti‐inflammatory pathways. Following oral NaHCO3 loading, macrophage polarization was shifted from predominantly M1 (inflammatory) to M2 (regulatory) phenotypes in the spleen and kidneys of rats, and in the blood of human subjects. Surprisingly, we found that gentle manipulation to visualize the spleen at midline during surgical laparotomy (sham splenectomy) was sufficient to abolish the response and resulted in hypertrophy/hyperplasia of the capsular mesothelial cells. Thin collagenous connections lined by mesothelial cells were found to connect to the capsular mesothelium. Mesothelial cells in these connections stained positive for the pan‐neuronal marker PGP9.5 and acetylcholine esterase and contained many ultrastructural elements which visually resembled neuronal structures, including synaptic ribbons (the presence of which was confirmed by immunohistochemistry). Both disruption of these fragile connections or transection of the vagal nerves below the diaphragm, resulted in loss of capsular mesothelial acetylcholine esterase staining and a significant reduction in splenic mass, which was not additive. Our data indicate that oral NaHCO3 activates the cholinergic anti‐inflammatory pathway and provides evidence that the signals that mediate this response are transmitted to the spleen via a novel neuronal like function of mesothelial cells.Support or Funding InformationThis work was supported by grants to Paul O'Connor (NIH DK099548 and 1P01HL134604)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.