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Biomedical subjects

C E Riva

Publications and source records attributed to C E Riva.

At least 19 recordsLinked to original sources

Variations of blood flow at optic nerve head induced by sinusoidal flicker stimulation in cats.

1. The present investigation explored, in thirty-four anaesthetized cats, the blood flow changes at the optic nerve head elicited by sinusoidally modulated photic stimuli. 2. The stimuli were achromatic, diffuse and had 30 deg diameter field size; the stimulus frequency was varied from 0 to 100 Hz, modulation depth from 0 to 100% and mean retinal illuminance up to 50,000 trolands (td); the blood flow was measured with a near-infrared (810 nm) laser Doppler flowmeter. 3. At various frequencies, modulation depths and mean retinal illuminance, sinusoidal flicker stimulation always caused an increase in blood flow at the optic nerve head relative to steady stimulation. 4. The frequency response and temporal contrast sensitivity function of the blood flow changes had a bandpass shape; the high-frequency slope of the frequency response was 3 decades (dec) per decade and that of the temporal contrast sensitivity function was 1.7 dec per dec, close to the slope for cat 'on' ganglion cells (2.6 dec per dec). 5. In most cats, the magnitude of the increase in blood flow was a sigmoidal function of modulation depth; in the remainder, the relationship was close to linear. 6. The threshold of blood flow changes varied with respect to mean retinal illuminance similar to Ferry-Porter's law and the photopic linear slope was 50 Hz dec-1. 7. In comparison with reported psychophysical and electrophysiological responses elicited by similar stimulations, the results of the present study resemble more those obtained from ganglion cells than those from electroretinograms, visual-evoked potentials and psychophysics. It is suggested that the blood flow changes at the optic nerve head are induced by the activity of ganglion cells.

Animals

Rebreathing into a bag increases human retinal macular blood velocity.

AIMS: The effect of rebreathing into a bag (RB) on retinal macular blood velocity was evaluated in healthy volunteers. METHODS: Ten normal volunteers, whose ages ranged from 17 to 34 years, performed RB over 135 to 260 seconds (mean (SD) 193 (38) seconds) while retinal macular blood velocity was determined non-invasively using the blue field simulation technique. RESULTS: Leucocyte velocity significantly increased (p < 0.05) at 2 minutes and at the end of RB by 53% (42%) and 92% (65%), respectively (95% confidence interval of the mean (CIM)). All subjects observed an increase in the density of leucocytes. At the end of RB, mean systolic brachial arterial pressure and heart rate were significantly increased by 24% (11%) and 37% (15%) respectively (p < 0.01). At 2 minutes, end tidal oxygen concentration in the exhaled air was 47% (8%) (95% CIM) below and carbon dioxide was 41% (16%) above baseline (p < 0.001). The RB produces a large increase in macular leucocyte velocity, suggesting an increase in blood flow. CONCLUSION: Although RB has some systemic risk due to hypoxia and hypercapnia, RB for a short period of 1 or 2 minutes might be of help in the treatment of retinal arterial obstructive diseases in young patients without cardiovascular disorders if other treatments do not show any beneficial effects.

Adolescent

Strict control of glycaemia: effects on blood flow in the large retinal vessels and in the macular microcirculation.

AIMS: The purpose of this study was to investigate the effect of instituting strict diabetic glycaemic control on the retinal macular microcirculation and to compare this effect with that observed in the main retinal veins. METHODS: In 28 insulin dependent diabetic patients with poor glycaemic control a regimen of strict diabetic control, consisting of four daily insulin injections was instituted and maintained for 6 months. Retinal haemodynamics were investigated in the macular microcirculation by the blue field simulation technique and in the major retinal veins by a combination of bidirectional laser Doppler velocimetry and monochromatic fundus photography. Progression of diabetic retinopathy was assessed from fundus photographs taken at baseline and at the end of the study. RESULTS: Institution of strict diabetic control resulted in a significant increase in leucocyte velocity in the macular circulation (p = 0.013). No significant difference in this increase was observed between eyes that showed progression (n = 8) and no progression (n = 20) of retinopathy during the study. Significant correlations were found between relative changes over time of blood flow measured in the main retinal veins and relative changes of leucocyte velocity determined in the macular microcirculation at 2 months (p = 0.008) and 6 months (p = 0.001) but not at 5 days (p = 0.49). In the eight eyes that showed progression of retinopathy, the product of leucocyte velocity and density at baseline was significantly higher than normal (p < 0.05). During the length of this study, this product was also significantly higher in the eight eyes that showed retinopathy progression than in the 20 eyes that did not show progression (p = 0.005). CONCLUSION: Our results suggest that increased flow in the macular microcirculation may be associated with progression of retinopathy, thus supporting the hypothesis that increased blood flow may play a role in the development of diabetic microangiopathy. Although there are correlations between the changes detected in the macular microcirculation and those measured in the main retinal vessels, there are also differences which need to be further investigated in order to better understand pathogenetic mechanisms.

Adolescent

Frequency and luminance-dependent blood flow and K+ ion changes during flicker stimuli in cat optic nerve head.

PURPOSE: The purpose of this study was to investigate whether blood flow in the cat optic nerve head (ONH) is related to increased neuronal activity elicited by diffuse luminance flickering light stimulation. METHODS: ONH blood flow was measured by laser Doppler flowmetry in anesthetized cats during 1 to 3 minutes of flickering light stimulation at controlled luminance and frequency (n = 227 measurements in 18 cats) using either a conventional visual stimulator (repetitive short flashes) or a sinusoidally varying light stimulator. Potassium ion concentration ([K+]) changes in the vitreous humor immediately in front of the optic disk were measured with neutral carrier K+ ionophore liquid membrane microelectrodes. Effects of varying flicker frequency (2 to 80 Hz) at constant luminance were quantified. Effects of luminance were quantified by varying the modulation depth of the stimulus at constant frequency. RESULTS: Both ONH blood flow and [K+] increased during flicker stimulus with an average slope of 0.305% +/- 0.064% (SE)/microM [K+] (257 measurements in 18 cats). The peak ONH blood flow increase was 59% +/- 11% above baseline at 33.3 +/- 3.1 Hz. The peak [K+] increase was 188 +/- 42 microM above baseline at 38.3 +/- 3.3 Hz. Both ONH blood flow and [K+] changes had similar bandpass characteristics with frequency, first increasing, then dropping off at higher frequencies (122 measurements in 10 cats). Both frequency responses were described by power law functions (y = af"). Luminance responses for both ONH blood flow and [K+] changes could be fit by a modified Hill model and were 50% of maximum at light modulation depths of 21.2% +/- 4.6% and 22.5% +/- 3.7%, respectively (53 measurements in 5 cats). CONCLUSIONS: Increases in ONH blood flow were correlated with changes in [K+]. Both responses were remarkably similar, with no significant differences in the frequency for peak responses in ONH blood flow or [K+], in low- and high-frequency power law exponents of the two responses, or in the 50% response to light modulation. The results are consistent with close coupling of neuronal activity and ONH blood flow.

Animals

Effects of adenosine on ocular blood flow.

PURPOSE: To determine the effect of intravascular adenosine on blood flow in the ocular fundus and to examine indirectly whether the blood-brain barrier to adenosine, which exists in the cerebrovasculature of the cat, is present in the eye of this animal. METHODS: The noninvasive techniques of laser Doppler flowmetry and velocimetry along with fundus photography were used to measure the change in optic nerve head and choroidal and retinal blood flow during intravenous infusions of 0.18 and 0.6 mg/kg per minute of adenosine. RESULTS: Infusions of adenosine induced significant increases in choroidal blood flow (60% with 0.6 mg/kg per minute) but not in optic nerve head or retinal blood flows. CONCLUSIONS: The lack of effect of intravenously infused adenosine on the optic nerve and retinal circulations is most likely caused by the tight junctions in the vessels of these vascular beds, which prevent adenosine from reaching its receptors. Perivascular adenosine in the choroid most likely accounts for the increase in blood flow in this tissue.

Adenosine

Nitric oxide and choroidal blood flow regulation.

PURPOSE: Nitric oxide (NO) has been found to be an endothelial-derived relaxing factor mediating the vasodilatation that results from the stimulation of muscarinic endothelial receptors. It also has been identified as a putative neurotransmitter of parasympathetic origin in choroidal perivascular autonomic fibers. The authors investigated a potential role of NO in choroidal blood flow (ChBF) regulation. METHODS: Local ChBF in the tapetal region of 26 anesthetized cats was measured by laser Doppler flowmetry. Cats were infused through the femoral vein with increasing dosages of acetylcholine (ACh); N omega-nitro-L-arginine (NNL-A), a specific inhibitor of NO synthesis; L-arginine; and D-arginine. ChBF and mean arterial pressure (MAP) were continuously recorded. RESULTS: Infusion of 20 micrograms/minute ACh induced a 68% increase in ChBF despite a 9% decrease in MAP. Infusion of 16 mg/minute NNL-A attenuated the ACh-induced increase in ChBF by 46% and increased MAP by 40%. Infusion of different dosages of NNL-A without prior administration of ACh caused ChBF to fall below and MAP to rise above baseline in a dose-dependent fashion. Infusion of L-arginine prior to ACh infusion enhanced by 27% the ACh-induced increase in ChBF, whereas D-arginine had no effect on this increase. CONCLUSIONS: These findings suggest the presence of a local vasodilatory cholinergic mechanism in the choroid, inducing the release of NO. They also suggest that release of NO in the choroid may maintain basal blood flow to this tissue.

Acetylcholine

Laser Doppler flowmetry in the optic nerve.

Laser Doppler flowmetry (LDF) is a technique that measures relative average velocity, number and flux (number times velocity) of red blood cells in a tissue. In this paper, we demonstrate its application in the optic nerve head tissue, describe the laser delivery and light scattering detection schemes and investigate the effect of the distance between the sites of illumination and detection. We also provide evidence that the flow measured by LDF varies linearly with actual blood flow in the optic nerve and examine the question of the depth of the sampled volume. Experiments in anesthetized cats illustrate potential applications which make use of the high temporal resolution of LDF. These include the response of blood flow to changes in the composition of the breathing gases and changes induced by neuronal stimulation with multiple and single flashes.

Animals

Effect of acute increases in intraocular pressure on intravascular optic nerve head oxygen tension in cats.

A newly developed phosphorescence imaging technique was used to generate two-dimensional maps of intravascular oxygen tension (PO2) in the optic nerve head (ONH) and retina of the cat to study the effects of acute moderate increases in intraocular pressure (IOP) on the ONH and retinal PO2. Both the ONH and retinal PO2 were remarkably well maintained as the IOP increased; hypoxia developed only after the blood flow to the eye was stopped. Because ONH hypoxia was not observed during IOP elevation, a lack of oxygen may not be a major cause of glaucomatous damage, although the effects of chronically elevated IOP on the PO2 remain to be evaluated. Because this imaging technique was noninvasive and required only a small bolus injection of a nontoxic oxygen probe, the authors anticipate that it will find significant application in the study of many ocular vascular diseases and glaucoma.

Acute Disease

Intravenous nicardipine in cats increases optic nerve head but not retinal blood flow.

The effect of intravenously injected nicardipine on retinal and optic nerve head (ONH) blood flow was studied in 27 cats using laser Doppler velocimetry and flowmetry, respectively. A dose of 20 micrograms/kg of nicardipine had little effect on retinal blood flow. A dose of 100 micrograms/kg, however, produced a significant transient decrease in flow. By contrast, both doses produced a significant increase in ONH blood flow despite a significant decrease of the mean arterial blood pressure. Measurements of the partial pressure of oxygen (PO2) with an oxygen-sensitive microelectrode, whose tip was placed in the vitreous just in front of the optic disc, showed a significant increase in the PO2 that paralleled the increase in ONH blood flow. These results demonstrate, for the first time to the authors' knowledge, a pharmacologically induced increase in ONH blood flow and suggest that nicardipine could have a beneficial effect on ONH tissue.

Animals

The acute effect of topical epinephrine on macular blood flow in humans.

The acute effect of topical epinephrine HCl 2% on macular capillary blood flow was studied in 18 healthy human volunteers using the blue-field simulation technique. This technique provides a method for quantifying the velocity of leukocytes flowing in macular capillaries. Subjects adjusted the velocity of simulated leukocytes on a computer screen to match that of their own entoptically perceived leukocytes before instilling the drug and 2 hr thereafter. An artificial tear solution was instilled into the fellow eye for a control. Epinephrine instillation resulted in a 8% increase in macular leukocyte velocity and presumably blood flow (P less than 0.03, paired student t-test).

Administration, Topical

Total retinal volumetric blood flow rate in diabetic patients with poor glycemic control.

Total retinal volumetric blood flow rate was measured in 12 normal subjects and 18 poorly controlled diabetic patients with background diabetic retinopathy. Maximum or center-line erythrocyte velocity (Vmax) was assessed by bidirectional laser Doppler velocimetry in four to five major retinal veins of one eye of each subject. Venous diameter (D) was measured from monochromatic fundus photographs. Total venous cross-section and measured total retinal volumetric blood flow in the diabetic patients were significantly larger than normal (P = 0.001 and P = 0.02, respectively). A positive linear correlation was found between Vmax and D in normal and diabetic eyes. Volumetric blood flow rate, Q, varied with D at a power of 2.87 in normal eyes. Total volumetric blood flow correlated with total venous cross-section. It was found that Q in the temporal retina was significantly larger than in the nasal retina in normal subjects (P = 0.0008) and diabetic patients (P = 0.0002). A significant difference in Q was observed between the superior and inferior retina in diabetic patients (P = 0.03) but not in normal subjects. The retinal vascular regulatory response to 100% oxygen breathing was reduced (P = 0.019) in diabetic patients and correlated with the level of background diabetic retinopathy. A close estimate of total volumetric blood flow may be obtained from blood flow measurement in one major retinal vein and the determination of total venous cross-section. This may be important for clinical studies in which measurements of all individual retinal veins may not be feasible.

Adolescent

Flicker evoked increase in optic nerve head blood flow in anesthetized cats.

The effect of diffuse luminance flicker stimulation of a large area (approximately 30 degrees diameter) on red blood cell flux (F) in the optic nerve head was measured in the anesthetized cat. F increased markedly during sustained flicker. The F-response to the initiation and cessation of the stimulation was found to occur within a few seconds. Upon sustained stimulation, the increase in F reached a plateau within approximately 2 min. Its level depended upon the intensity, frequency and wavelength of the stimulation and the state of adaptation of the retina. This stimulus offers a new and powerful means of investigating blood flow regulation in the optic nerve head (ONH).

Adaptation, Ocular

Diffusion of O2 in normal and ischemic retinas of anesthetized miniature pigs in normoxia and hyperoxia.

Transretinal PO2 profiles were recorded with O2-sensitive microelectrodes in the normal retina and in ischemic retinal foci induced by the occlusion of a retinal branch vein with argon laser photocoagulation in anesthetized miniature pigs. In the normal retina there are two PO2 gradients: one from the inner retina and the other from the choroid, both directed toward the middle of the retina. Both PO2 gradients persisted during hyperoxia. Thus, even in hyperoxia, the choroid does not supply the whole thickness of the normal retina with O2. Preretinal and transretinal PO2 measurements in ischemic inner retinal foci showed the existence of two PO2 gradients in steady-state systemic normoxia, as did those in the normal retina. This finding indicates that even in ischemia the choroid does not supply O2 to the inner retina; as a result, tissue hypoxia is maintained. During systemic hyperoxia, the intraretinal PO2 measurements in the ischemic foci showed only one gradient going from the choroid toward the inner retina. This gradient indicates that under these conditions, the choroid can supply O2 to the entire thickness of the ischemic retina. Extending a previously formulated hypothesis, we propose that in the ischemic retina as opposed to the normal retina, hyperoxia does not induce an increase in the O2 consumption of the outer retina. This suggestion could explain the rise in PO2 in the inner ischemic retina during hyperoxia.

Animals

Rhythmic changes in velocity, volume, and flow of blood in the optic nerve head tissue.

Using laser Doppler flowmetry, slow variations in velocity, volume, and flux of red blood cells in the optic nerve head (ONH), choroid, and retina of the anesthetized minipig have been demonstrated. The variations of velocity and volume were highly regular and vigorous in the ONH and had frequencies ranging from 2.5 to 4.5 cycles/min. The flux variations were smaller or absent due to a phase shift of approximately 180 degrees between the volume and velocity changes. The volume fluctuations were synchronized to those of the PO2 measured in the vitreous, at approximately 50 microns from the surface of the ONH tissue. The fluctuations were less regular in the choroidal and the retinal vessels and their frequencies were higher than those in the ONH. The lack of correlation between the fluctuations in the ONH and those in the retinal and choroidal vessels points toward a local mechanism. The changes in blood volume in the ONH, the phase shift between volume and velocity changes, and the predominance of venules at the surface of the ONH are three factors suggesting that this mechanism involves a change in the diameter of the venules rather than in the arterioles.

Animals

Diabetic glycemic control and retinal blood flow.

The effect of strict glycemic control on retinal volumetric blood flow rate (Q) was investigated in 13 insulin-dependent diabetic patients with laser Doppler velocimetry and monochromatic fundus photography. Strict glycemic control was achieved by glucose monitoring and four daily insulin injections. Q was determined in a major retinal vein at baseline and then 5 days, 2 mo, and 6 mo after the institution of strict control. Level of retinopathy was assessed from stereocolor fundus photographs taken at baseline and 6 mo. After 6 mo of strict diabetic control, five eyes demonstrated progression (P) by one or more retinopathy levels, and eight eyes showed no progression (NP). At 5 days, there was a significant decrease in Q of 1.4 +/- 0.9 microliters/min (P less than 0.005) in NP eyes and a nonsignificant increase in Q of 1.2 +/- 1.7 microliters/min in P eyes. Changes in Q from baseline observed at 5 days were strongly correlated with changes in retinopathy level at 6 mo (r = 0.79, P less than 0.005). No significant changes in Q from baseline were observed at 2 and 6 mo. A lack of decrease in Q at 5 days was associated with the progression of retinopathy that occurs in some patients after the institution of strict glycemic control and may serve as a predictor for progression of retinopathy.

Adult

Diffusion of O2 in the retina of anesthetized miniature pigs in normoxia and hyperoxia.

Intraretinal oxygen tension (pO2) and local electroretinogram (ERG) were simultaneously measured in miniature pigs using double-barreled recess type microelectrodes. Transretinal pO2 profiles were recorded during normoxia and hyperoxia in areas close to (juxta-arteriolar) or far from (intervascular) retinal arterioles. In normoxia, in both areas, the pO2 decreased from the inner retina and the choroid towards the middle of the retina. In the inner retina the gradient of the juxta-arteriolar pO2 profile was steeper than that of the intervascular profile. This characteristic persisted during the breathing of 100% O2. Analysis of the pO2 profiles shows that, even in hyperoxia, the choroid cannot supply O2 to the whole retina. The results also support the conclusions of previous work (Riva, Pournaras and Tsacopoulos, 1986) indicating that in the normal retina it is not the O2 diffusing from the choroid to the retinal arterioles the induces vasoconstriction of these vessels. In the miniature pig this constriction appears to maintain inner retina tissue pO2 at a constant level during hyperoxia. From the pO2 transretinal profiles and previously published choroidal O2 fluxes and pO2 values near retinal vessels an explanatory working hypothesis is formulated according to which O2 consumption (qO2) of the outer retina increases during hyperoxia in the miniature pig.

Animals

Retinal blood flow regulation and the clinical response to panretinal photocoagulation in proliferative diabetic retinopathy.

Bidirectional laser Doppler velocimetry and monochromatic fundus photography were used to investigate retinal hemodynamics before and after panretinal photocoagulation (PRP) in 25 eyes of 23 diabetic patients with proliferative retinopathy. After PRP, there was a significant decrease in retinal volumetric blood flow rate and an increase in the retinal vascular regulatory response to hyperoxia (R). A significant association was found between the presence or absence of regression of neovascularization and the increase or decrease in R after PRP. Eyes that showed regression of neovascularization had significantly larger average R after PRP than eyes that did not show regression. Lack of improvement in R after PRP may be related to the presence of remaining ischemia or hypoxia in eyes that continue to show proliferation after PRP.

Adult

Retinal circulation during a spontaneous rise of intraocular pressure.

The retinal haemodynamic changes occurring in an eye with a spontaneous elevation of intraocular pressure were investigated by bidirectional laser Doppler velocimetry and monochromatic fundus photography. At an intraocular pressure of 47 mmHg the blood velocity and volumetric blood flow rate were significantly smaller and arterial blood velocity pulsatility was significantly greater than normal. The corresponding 88% reduction in perfusion pressure was accompanied by a 67% reduction in total retinal blood flow, indicating that autoregulation is not efficient at this level of intraocular pressure. An Octopus visual field examination obtained immediately following blood flow measurements suggested that the central retina can preserve a fairly good function under a total retinal blood flow rate of about one-third of the normal value.

Adult