Impaired Layer Specific Retinal Vascular Reactivity Among Diabetic Subjects

PurposeTo investigate layer specific retinal vascular reactivity (RVR) in capillaries of diabetic subjects with no or mild non-proliferative diabetic retinopathy (NPDR).MethodsA previously described nonrebreathing apparatus was used to deliver room air, 5% CO2, or 100% O2 to 41 controls and 22 diabetic subjects (with mild or no NPDR) while simultaneously acquiring fovea-centered 3×3mm2 Swept-Source Optical Coherence Tomography Angiography. Vessel skeleton density (VSD) and vessel diameter index (VDI) were calculated for each gas condition for the superficial retinal layer (SRL) and deep retinal layer (DRL). The superficial layer analysis excluded regions of arterioles and venules. Data analysis was performed using mixed factorial analysis of covariance stratified by diabetic status. All models were adjusted for age, gender, and hypertension.ResultsAmong controls, there was a significant difference in capillary VSD between all gas conditions (p<0.001). This difference was present in both the SRL and DRL. Among diabetics, there was no significant difference in response to CO2 conditions in the SRL (p=0.072), and a blunted response to both CO2 and O2 in the DRL. A significant gas effect was detected in the capillary VDI in the SRL of controls (p=0.001), which was driven by higher VDI in the oxygen condition compared to that of carbon dioxide.ConclusionsImpairment in RVR in diabetic subjects is driven largely by a decrease in the magnitude of the capillary response to O2 in the DRL as well as almost complete attenuation of capillary CO2 response in all layers. These layer and gas specific impairments in diabetics seem to occur early in the disease and to be driven primarily at the capillary level.

Endotelium in Turner syndrome with capillaroscopy

OBJECTIVE: The aim of this study was to assess the endothelium function in patients with Turner syndrome using videocapillaroscopy and to compare the results with healthy control. METHODS: Subjects and controls were studied in a temperature-controlled room, 20 days after no nailfold manipulations. The capillaries were visualized by a microscope connected to a television and a computer. The test of post-occlusive reactive hyperemia was performed using a sphygmomanometer attached to the fourth left finger, 20mmHg above maximum arterial pressure during 1 minute, and the following patterns were studied: area of transverse segment, maximal post-ischemia area and time to reach maximal post-ischemia area. RESULTS: The value of measure of transverse segment projected area , the maximal postischemia area of hand nailfold capillary loops using computerized videophotometry and the time to reach maximal post ischemia area were studied in 40 patients with Turner syndrome and 26 healthy women controls of comparable age (20±7.5 versus 18±8.1 years old; p=0.57). There were differences between transverse segment area (706.8±139.1 versus 548.8±117.2; p=0.001). Maximal post-ischemia area (891.3±226.1 versus 643.5±134.3; p=0.001) and the time to reach it (10.8±4.3 versus 5.5±2.5; p=0.001) were different between patients and controls. CONCLUSIONS: Changes of capillary response to ischemia could be observed in patients with Turner syndrome using videocapillaroscopy when they were compared to a healthy control group.

Limitations of Collateral Flow after Occlusion of a Single Cortical Penetrating Arteriole

Occlusions of penetrating arterioles, which plunge into cortex and feed capillary beds, cause severe decreases in blood flow and are potential causes of ischemic microlesions. However, surrounding arterioles and capillary beds remain flowing and might provide collateral flow around the occlusion. We used femtosecond laser ablation to trigger clotting in single penetrating arterioles in rat cortex and two-photon microscopy to measure changes in microvessel diameter and red blood cell speed after the clot. We found that after occlusion of a single penetrating arteriole, nearby penetrating and surface arterioles did not dilate, suggesting that alternate blood flow routes are not actively recruited. In contrast, capillaries showed two types of reactions. Capillaries directly downstream from the occluded arteriole dilated after the clot, but other capillaries in the same vicinity did not dilate. This heterogeneity in capillary response suggests that signals for vasodilation are vascular rather than parenchymal in origin. Although both neighboring arterioles and capillaries dilated in response to topically applied acetylcholine after the occlusion, the flow in the territory of the occluded arteriole did not improve. Collateral flow from neighboring penetrating arterioles is neither actively recruited nor effective in improving blood flow after the occlusion of a single penetrating arteriole.

Neutrophil enhancement of reperfusion-induced capillary fluid filtration associated with hypercholesterolemia

Fluid filtration rate (Jv/S) from individual mesenteric capillaries in normocholesterolemic and hypercholesterolemic rats was measured before and after 30 min each of ischemia and reperfusion (I/R). The median I/R-induced increase in Jv/S (I/R vs. baseline) was 44% in normocholesterolemic rats (n = 11) and 97% in hypercholesterolemic rats (n = 11). A positive correlation slope of 0.20% per mg/dl resulted when the percent Jv/S increase vs. plasma cholesterol concentration (P = 0.02) was plotted, demonstrating that hypercholesterolemia enhances the capillary response to I/R. Because microvascular pressure did not change significantly after I/R in either group of rats, the increments in Jv/S likely reflect increased capillary permeability. In hypercholesterolemic rats rendered neutropenic with antineutrophil serum, I/R did not elicit a significant increase in Jv/S, suggesting that activated neutrophils mediate the exaggerated endothelial barrier dysfunction associated with hypercholesterolemia.