Glycine improves peritoneal vasoreactivity to dialysis solutions in the elderly.

Background: Peritoneal dialysis solution (PDS) dilates peritoneal microvessels predominantly by the activation of the endothelial nitric oxide (NO) pathway. We made an incidental observation of decreased PDS-induced, NO-dependent peritoneal microvascular vasoreactivity in elderly rats naïve to PDS exposure. We hypothesized that this subordinate NO-mediated peritoneal microvascular vasoreactivity is caused by increased oxidative stress in the aged endothelium, which compromises NO bioavailability in the elderly, and that peritoneal microvascular vasoreactivity can be improved by the supplementation of antioxidant glycine to PDS. Methods: We studied PDS-mediated vasoreactivity of four intestinal visceral arterioles of different orders by in vivo intravital microscopy in weaned, adult, and elderly rats to (i) confirm subordinate vasoreactivity to PDS in elderly rats; (ii) restore vasoreactivity by glycine supplementation; and (iii) establish age as an independent risk factor for endothelial cell dysfunction. Results: In a crossover series, peritoneal microvascular vasoreactivity to PDS exposure was remarkably decreased in elderly rats. This subordinate vasoreactivity was completely restored by the supplementation of glycine to PDS. In a separate series, we assessed in situ endothelial cell function in weaned and adult rats using the cumulative acetylcholine concentration-response curves. Unlike the adults, the weaned rats demonstrated remarkable sensitivity and reactivity to cumulative acetylcholine concentrations, suggesting the dependency of endothelial cell function on age. Conclusion: Aging is an independent risk factor for peritoneal microvascular endothelial cell dysfunction. Endothelial function in the elderly can be recovered by reinforcing the bioavailability of endothelial-derived NO through glycine. Dietary glycine supplementation is a potential therapeutic strategy to decrease the burden of oxidative stress on the aged endothelium.

Corneal Confocal Microscopy detects a Reduction in Corneal Endothelial Cells and Nerve Fibres in Patients with Acute Ischemic Stroke.

Endothelial dysfunction and damage underlie cerebrovascular disease and ischemic stroke. We undertook corneal confocal microscopy (CCM) to quantify corneal endothelial cell and nerve morphology in 146 patients with an acute ischemic stroke and 18 age-matched healthy control participants. Corneal endothelial cell density was lower (P < 0.001) and endothelial cell area (P < 0.001) and perimeter (P < 0.001) were higher, whilst corneal nerve fibre density (P < 0.001), corneal nerve branch density (P < 0.001) and corneal nerve fibre length (P = 0.001) were lower in patients with acute ischemic stroke compared to controls. Corneal endothelial cell density, cell area and cell perimeter correlated with corneal nerve fiber density (P = 0.033, P = 0.014, P = 0.011) and length (P = 0.017, P = 0.013, P = 0.008), respectively. Multiple linear regression analysis showed a significant independent association between corneal endothelial cell density, area and perimeter with acute ischemic stroke and triglycerides. CCM is a rapid non-invasive ophthalmic imaging technique, which could be used to identify patients at risk of acute ischemic stroke.

Corneal Confocal Microscopy Detects Corneal Nerve Damage in Patients Admitted With Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Corneal confocal microscopy can identify corneal nerve damage in patients with peripheral and central neurodegeneration. However, the use of corneal confocal microscopy in patients presenting with acute ischemic stroke is unknown. METHODS: One hundred thirty patients (57 without diabetes mellitus [normal glucose tolerance], 32 with impaired glucose tolerance, and 41 with type 2 diabetes mellitus) admitted with acute ischemic stroke, and 28 age-matched healthy control participants underwent corneal confocal microscopy to quantify corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length. RESULTS: There was a significant reduction in corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length in stroke patients with normal glucose tolerance (P<0.001, P<0.001, P<0.001), impaired glucose tolerance (P=0.004, P<0.001, P=0.002), and type 2 diabetes mellitus (P<0.001, P<0.001, P<0.001) compared with controls. HbA1c and triglycerides correlated with corneal nerve fiber density (r=-0.187, P=0.03; r=-0.229 P=0.01), corneal nerve fiber length (r=-0.228, P=0.009; r=-0.285; P=0.001), and corneal nerve branch density (r=-0.187, P=0.033; r=-0.229, P=0.01). Multiple linear regression showed no independent associations between corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length and relevant risk factors for stroke. CONCLUSIONS: Corneal confocal microscopy is a rapid noninvasive ophthalmic imaging technique that identifies corneal nerve fiber loss in patients with acute ischemic stroke.