Normative intercapillary distance and vessel density data in the temporal retina assessed by wide-field spectral-domain optical coherence tomography angiography

A limitation of conventional optical coherence tomography angiography (OCTA) is the limited field of view normally used in data acquisition. As the technology improves, larger fields of view that capture information away from the macular are being explored in order to provide an enhanced ability to detect pathology. However, normative measurements for important OCTA metrics like vessel density and intercapillary distance are not currently well-characterized in the peripheral retina. In this prospective study, we measured vessel density and intercapillary distance of the superficial vascular complex, ganglion cell layer plexus, and deep capillary plexus in montaged macular/temporal scans from 53 (33 men) healthy volunteers. Vessel density and intercapillary distance were also compared across different regions of the retina, including along arcs at separate distance from the fovea. Compared to the central macular region, the temporal retina had significantly lower vessel density, decreased thickness, and greater intercapillary distance in the superficial vascular complex, GCLP ganglion cell layer plexus, and deep capillary plexus (Wilcoxon rank sum test P < 0.001), with each of the plexuses examined here showing a general decrease in vessel density and an increase in intercapillary distance towards the temporal region. No significant difference was noted comparing corresponding vessel density and intercapillary distance regions above and below the macula, and multiple linear regression showed that age and intraocular pressure were not associated with vessel density and intercapillary distance in most models. Repeatability analysis reported as intraclass correlation coefficients demonstrated moderate to excellent reliability of vessel density and intercapillary distance in all OCTA layers. These results should help provide an enhanced baseline to help identify vascular pathology in the peripheral retina.

Multiscale homogenization for fluid and drug transport in vascularized malignant tissues

A system of differential equations for coupled fluid and drug transport in vascularized (malignant) tissues is derived by a multiscale expansion. We start from mass and momentum balance equations, stated in the physical domain, geometrically characterized by the intercapillary distance (the microscale). The Kedem–Katchalsky equations are used to account for blood and drug exchange across the capillary walls. The multiscale technique (homogenization) is used to formulate continuum equations describing the coupling of fluid and drug transport on the tumor length scale (the macroscale), under the assumption of local periodicity; macroscale variations of the microstructure account for spatial heterogeneities of the angiogenic capillary network. A double porous medium model for the fluid dynamics in the tumor is obtained, where the drug dynamics is represented by a double advection–diffusion–reaction model. The homogenized equations are straightforward to approximate, as the role of the vascular geometry is recovered at an average level by solving standard cell differential problems. Fluid and drug fluxes now read as effective mass sources in the macroscale model, which upscale the interplay between blood and drug dynamics on the tissue scale. We aim to provide a theoretical setting for a better understanding of the design of effective anti-cancer therapies.

Dipyridamole-induced capillary growth in normal and hypertrophic hearts

Chronic increases in myocardial blood flow have been shown to stimulate capillary proliferation in normal growing hearts. It is unknown, however, if elevated myocardial blood flow stimulates precapillary and/or capillary growth in hearts undergoing hypertrophy. Accordingly, renal hypertension was produced in rabbits (Page, 1-kidney, 1-wrap model) in which one group of Page (n = 9) and one group of normotensive sham (n = 10) rabbits were given dipyridamole (4.0 mg/kg sc) twice daily for 2 mo. Another group of Page (n = 7) and sham (n = 12) rabbits received vehicle injections. In separate acute studies performed on conscious rabbits, this does of dipyridamole increased myocardial blood flow 35-60% over time without altering transmural distribution of flow or systemic blood pressure. Two months later, minimal coronary vascular resistance (MCVR/100 g) was calculated from perfusion during maximal coronary vasodilation in conscious animals. Histomorphometric methods were then utilized to evaluate various indexes of capillarity in perfuse-fixed hearts. Systolic pressure and left ventricle weight-to-body weight ratios were significantly higher in Page vs. sham rabbits; dipyridamole treatment did not alter these parameters within either group. Similarly, dipyridamole treatment did not significantly alter MCVR/100 g values in either normotensive or hypertensive rabbits. In contrast, dipyridamole treatment increased endomyocardial capillary length density by 33% in the hypertensive group (P less than 0.05) and 11% in the sham group (P not significant) compared with the respective vehicle-treated rabbits. In addition, intercapillary distance was significantly reduced in the endomyocardial region of both groups receiving dipyridamole injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Capillary growth and geometry during long-term hypertension and myocardial hypertrophy in dogs

Angiogenic response of the myocardial capillary bed to long-term (7 mo) renovascular hypertension (one-kidney, one-clip) was assessed in eight mongrel dogs and compared with seven control dogs. Image analyses of histological sections from four transmural specimen sites of left ventricular (LV) free wall were performed. While mean cross-sectional cardiocyte area increased in all transmural layers (epi-endo) in dogs with LV hypertrophy (LVH), the greatest increases occurred in the inner layers. Although capillary length density was significantly lower in two of the four transmural regions of LVH dogs, these decrements were much less than the lateral expansion of cardiocytes as indicated by cross-sectional areas. Calculations of total capillary length indicate that approximately one-fifth of the capillary bed in LVH dogs was formed during the 7-mo period of hypertension in hypertrophied hearts. Capillary volume and surface densities in LVH dogs decreased to a greater extent due to a larger population of capillaries with lumen diameters less than 4 microns. Capillary volume density in LVH dogs was remarkably similar across the wall despite large transmural differences in cardiocyte hypertrophy. LVH did not alter the log SD of capillary domains, a measure of the heterogeneity of spacing, or capillary orientation (degree or anisotropy). These data support several important conclusions regarding long-term hypertension-induced LVH in dogs. First, although capillary growth does not fully compensate for the increase in LV mass, a myriad of new capillaries are formed as indicated by a substantial increase in total capillary length. This growth minimizes the increase in intercapillary distance characteristic of LVH.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral regional capillary perfusion and blood flow after carbon monoxide exposure

Alterations in regional cerebral blood flow (rCBF) and percent perfused capillaries (indicative of functional intercapillary distance) were determined in conscious male Long-Evans rats after reducing their blood O2-carrying capacity by exposing them to 1% CO for 12 min. rCBF was determined by the iodoantipyrine method. rCBF increased from a mean of 106 +/- 8 (SE) ml.min-1.100 g-1 before CO exposure to 173 +/- 14 ml.min-1.100 g-1 after CO exposure. There was a greater flow increase (126%) in the cerebral cortex than in the lower brain stem [pons (45%), medulla (39%)]. Presence of fluorescein isothiocyanate-labeled dextran identified the perfused capillaries before and after CO exposure. The volume fraction (Vv) and number/mm2 (Na) of all capillaries (perfused and nonperfused) in a given area of brain were determined after staining for alkaline phosphatase. The percent Vv and percent Na of perfused capillaries increased uniformly (from approximately 50% to approximately 80%) in all parts of the brain after CO exposure. In the presence of tissue hypoxia with undiminished plasma PO2, the brain vasculature allowed greater flow of blood while the microvasculature adjusted to reduce the diffusion distance for O2.

Sympathectomy stimulates capillary but not precapillary growth in hypertrophic hearts

Sympathetic nerves are known to influence vascular growth, but their role in coronary vascular adaptations to pressure-overload left ventricular (LV) hypertrophy is unknown. Accordingly, regional sympathectomy (SYMX) was produced by painting a ring of phenol on the posterior third of the LV in seven renal hypertensive (Page: 1 kidney, 1 wrap) and seven normotensive (sham: 1 kidney, no wrap) rabbits. Two months later, maximal myocardial blood flow (MBF) following dipyridamole-induced coronary vasodilation was determined with microspheres in the intact anterior and the sympathectomized posterior regions of conscious rabbits. Histomorphometric methods were then utilized to evaluate capillary density (CD), intercapillary distance (ICD), and volume density (VD) of subepicardial and endocardial samples of each region of perfused-fixed hearts. The Page procedure significantly increased systolic blood pressure (+29%) and LV wt/body wt (+20%) above sham rabbits. In both sham and Page groups, MBF was not significantly different between intact and sympathectomized regions within either group. SYMX did not significantly alter CD, ICD, or VD between regions in the sham animals. In contrast, SYMX significantly increased CD (+30%) and VD (+26%) and decreased ICD (-21%) in the subendocardial region of Page animals. Regional SYMX did not alter myocyte cross-sectional area in Page animals. We conclude that SYMX neither 1) significantly increases resistance vessel cross-sectional lumen area in either normal or hypertrophic hearts, nor 2) significantly influences capillary growth in normal hearts, but SYMX does 3) promote capillary growth in hearts undergoing hypertrophy in response to hypertension.

Impaired capillary perfusion and brain edema following experimental subarachnoid hemorrhage: a morphometric study

✓ To evaluate microcirculatory disturbance and cerebral edema associated with subarachnoid hemorrhage (SAH), both stereological morphometry on the intraparenchymal capillary network and microgravimetry were performed on a rabbit SAH model. Autologous arterial blood (5 ml) was injected into the cisterna magna, and the animals were sacrificed at intervals of 6 hours, 1 day, 2 days, or 6 days after SAH. Capillaries in the piriform cortex, parasagittal cortex, and ventral brain stem of the midline-hemisectioned brain were injected with Evans blue dye 1 minute before sacrifice, and were planimetrically evaluated under a fluorescence microscope connected to an image analysis system. Stereological and morphological parameters including the volume density, surface density, numerical density, minimum intercapillary distance, and the diameter of Evans blue-perfused capillaries were also computed. In the piriform cortex and ventral brain stem, the volume and surface densities were significantly reduced and the minimum intercapillary distance was significantly increased 1 to 2 days after SAH. In the parasagittal cortex far from the cisternal clot, changes in the parameters were minimal. Cerebral blood volume (CBV) in the normal condition and edema formation associated with SAH were studied by the microgravimetric technique. The mean CBV in the parasagittal cortex, piriform cortex, and brain stem was 6.9%, 6.8%, and 5.6%, respectively. Following SAH, specific gravity in the piriform cortex and the ventral brain stem of the other side of the hemisectioned brain was significantly decreased at 1 to 2 days, showing a change parallel to that of the stereological parameters. The results obtained from the morphometric technique indicated the occurrence of impaired capillary perfusion and reduced capillary blood volume following SAH, while microgravimetry suggested the formation of brain edema during this period. These changes in the intraparenchymal vessels may play an important role in the pathophysiology of SAH.