El Rasheid Zakaria, Paul J Matheson, Ryan T Hurt, Richard N Garrison
{"title":"Chronic infusion of sterile peritoneal dialysis solution abrogates enhanced peritoneal gene expression responses to chronic peritoneal catheter presence.","authors":"El Rasheid Zakaria, Paul J Matheson, Ryan T Hurt, Richard N Garrison","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Chronic exposure to sterile peritoneal dialysis (PD) solutions is associated with microvascular and interstitial changes within the blood-peritoneal barrier (peritoneum). These changes are commonly linked to loss of peritoneal function over time, presumably because of angiogenesis-related increased vascular area. However, the effects on peritoneal microvascular function of chronic peritoneal exposure to PD solutions are unknown. The present study examined peritoneal microvascular function after chronic exposure to sterile PD solution. Six rats underwent permanent catheter insertion under anesthesia. Three rats were treated with approximately 16 mL conventional PD solution daily for 6 weeks; catheter insertion controls received 1 mL saline daily. At 6 weeks, visceral peritoneal microvascular function was assessed in vivo using intravital microscopy. Endothelial cell functions were assessed using messenger RNA (mRNA) gene microarray analysis. In both groups, significant angiogenesis was seen, predominantly in the base of the mesentery. Sensitivity and reactivity of the intestinal visceral peritoneal pre-capillary arterioles (A3 arterioles, 8 - 15 microm in diameter) were decreased in the catheter controls, but not in the chronic PD infusion rats. Chronic catheter presence increased the expression of 18 genes in the controls as compared with 12 genes in the chronic infusion rats. In both groups, expression of fibronectin, integrin-beta, integrin-alpha5, collagen type XVIII-alpha1, and matrix metalloproteinase was enhanced. Endothelial expression of proinflammatory genes (interleukin-1beta, tissue pathway inhibitor, chemokine ligand 2) was enhanced by chronic catheter insertion, but not after chronic PD fluid infusion. Increased expression of genes encoding proteins involved in inflammation and tissue remodeling results from peritoneal catheter-related endothelial cell activation. Chronic exposure of the nonuremic peritoneum to sterile PD solutions overrides the catheter-related endothelial cell proinflammatory phenotype to restore peritoneal microvascular function.</p>","PeriodicalId":520853,"journal":{"name":"Advances in peritoneal dialysis. Conference on Peritoneal Dialysis","volume":"24 ","pages":"7-15"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2596713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
El Rasheid Zakaria, Chester J Mays, Paul J Matheson, Ryan T Hurt, Richard N Garrison
{"title":"Plasma appearance rate of intraperitoneal macromolecular tracer underestimates peritoneal lymph flow.","authors":"El Rasheid Zakaria, Chester J Mays, Paul J Matheson, Ryan T Hurt, Richard N Garrison","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The magnitude of peritoneal lymph flow is an issue of great controversy in peritoneal dialysis (PD) research. Because no single lymphatic duct drains the entire peritoneal cavity, peritoneal lymph flow is indirectly measured as lymphatic removal of intraperitoneal macromolecular tracer. In rats, the peritoneal clearance (K) of such a tracer is 5 times the approximately 8 microL/min determined from the tracer appearance rate in blood (Cl). The fractional contribution of tissues bordering the peritoneal cavity to the overall Cl was determined to be diaphragm, 55%; viscera, 30%; and abdominal wall, 15%. The present study determines whether direct measurement of visceral peritoneal lymph flow matches the 30% (approximately 2.5 microL/min) contribution of the visceral peritoneal lymph flow as measured indirectly by the Cl method. The mesenteric lymph duct that exclusively drains lymph from the gut, liver, and mesentery was cannulated in 15 rats, and lymph flow from the duct was collected at hourly intervals up to 6 hours under near-normal physiologic conditions and under conditions of simulated PD. Changes in mesenteric lymph flow that resulted from a challenge with 3 mL intravenous saline were captured using real-time video. We observed no significant differences between the hourly lymph volumes collected over 6 hours in naïve animals (n = 5, p > 0.05). Under conditions of simulated PD with dialysis fluid in the peritoneal cavity, the mesenteric duct lymph flow averaged 8.67 +/- 1.41 microL/min (n = 10). That flow is similar to reported data on total peritoneal Cl in rats; and 4 times the 2.5 microL/min visceral peritoneal contribution to the total peritoneal Cl. The intravenous saline challenge significantly increased mesenteric lymph duct output to 30.9 +/- 1.6 microL/min (n = 5, p < 0.01) and reduced the lymph-to-plasma concentration ratio (L/P) by 43%. The reflection coefficient for total proteins (sigma(prot)) across the intestinal capillaries as calculated from the filtration rate-dependent L/P ratio when the transcapillary fluid escape rate and the mesenteric lymph flow were both high was more than 0.87. We concluded that (A) under near-normal physiologic conditions, the mesenteric lymph duct flow is steady, but quite low; (B) under conditions of simulated PD, the mesenteric lymph duct flow increases significantly from the physiologic norm; (C) mesenteric lymph duct flow is sensitive to the peritoneal fill volume; (D) during simulated PD, the fractional visceral peritoneal lymph flow measured indirectly from plasma appearance of intraperitoneal tracer underestimates the directly measured mesenteric duct lymph flow; and (E) the increased transcapillary fluid escape rate is rapidly buffered by augmentation of mesenteric lymph duct output.</p>","PeriodicalId":520853,"journal":{"name":"Advances in peritoneal dialysis. Conference on Peritoneal Dialysis","volume":"24 ","pages":"16-21"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2596618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}