Retinal Blood Velocity Research Articles

Blood velocity measurement in the posterior segment of the rabbit eye using combined spectral Doppler and power Doppler ultrasound

It is challenging for the current Doppler imaging to detect blood flow in small retinal vessels. Power Doppler, with its high sensitivity to detect minimal blood flow, can be used with spectral Doppler to measure blood velocity in small vessels of the eye and orbit. Sixteen eyes of twelve normal pigmented rabbits were studied, using a dedicated small animal, high-resolution imaging unit (Vevo 770) and 17.6 MHz ultrasound probe. Spectral Doppler (ISPPA = 67.1 W/cm(2), ISPTA = 483.7 mW/cm(2), MI = 0.5) was combined with power Doppler (ISPPA = 137.7 W/cm(2), ISPTA = 83.1 mW/cm(2), MI = 0.77) to measure the blood velocity over each identified vessel, including the central retinal artery and vein, branch retinal artery and vein, choroidal vein, and the long and short posterior ciliary artery. Three readings from each vessel were averaged to reduce measurement error. Three indices were calculated from the arterial blood velocity readings: the resistive index, the pulsatility index and the A/B ratio. The highest arterial blood velocity was measured over the long posterior ciliary artery; peak systolic velocity was 18.29 cm/s and end diastolic velocity was 16.63 cm/s, while the lowest arterial blood velocity was measured over the branch retinal artery; peak systolic velocity was 5.08 cm/s and end diastolic velocity was 3.25 cm/s. On the other hand, the highest venous blood velocity was measured over the choroidal veins (7.0 cm/s), and the lowest venous blood velocity was measured over the branch retinal vein (2.88 cm/s). No statistically significant difference was observed between the nasal and temporal retinal arterial blood velocity. Combining power Doppler with spectral Doppler imaging caused no damage and is a safe technique to measure blood velocity. A combination of spectral Doppler and power Doppler ultrasound can be used as a noninvasive and efficient tool for reproducible measurement of the blood velocity in the posterior segment.

Retinal hemodynamic changes in diabetic macular edema

Abstract Purpose To report the 1 year prospective hemodynamic results in a cohort of patients with varying levels of risk for the development of diabetic macular edema (DME) and to correlate these parameters to systemic changes in blood pressure and diabetes control. Methods The sample comprised 4 groups. Group 1: 37 non‐diabetic controls; Group 2: 42 patients with no diabetic retinopathy (DR); Group 3: 38 patients with DR but no DME; Group 4: 27 patients with DME. Retinal arteriolar diameter, velocity, maximum‐to‐minimum (max:min) velocity ratio and flow were measured using the Canon Laser Blood Flowmeter. Blood pressure, blood and urine tests were taken and correlated to changes in retinal hemodynamics. A sub‐group of patients with progressive DR was analyzed separately. Results There was a trend for elevation of the max:min velocity ratio (p=0.060) with increasing risk of DME at baseline which was significant on follow‐up (p=0.020). Diameter decreased for all groups (p<0.056) except for patients with DME. Changes in retinal blood velocity, max:min velocity ratio and flow were correlated to blood pressure mostly in patients with DR and DME. Blood albumin level was negatively correlated to retinal blood velocity and flow in the DME group. Patients with progressive DME had elevated blood velocity and flow. Conclusion Patients with DME have a higher max:min velocity ratio. Changes in retinal hemodynamics were correlated to changes in blood pressure and were negatively correlated to changes in blood albumin. The results indicate a loss of vascular compliance with diabetes, particularly in patients with DME, and elevated retinal perfusion in patients with progressive DME.

Effect of aging on retinal circulation in normotensive healthy subjects

Although it is important to investigate the effects of normal aging on the ocular circulation, few studies have examined the effects of aging on the retinal microcirculation in healthy subjects. The purpose of this study was to evaluate the effects of aging on the retinal microcirculation in healthy men. Forty-five healthy men were divided into three groups based on age (young, middle-aged, elderly). We measured vessel diameter and blood velocity and calculated the retinal blood flow (RBF) and wall shear rate (WSR) in the retinal arteries. We performed pulse wave analysis obtained from the retinal blood velocity measurements. We also divided the subjects into two groups based on the presence or absence of prehypertension defined as 120–139/80–89 mmHg. No significant differences in vessel diameter, blood velocity, RBF, and WSR were seen among the groups. Pulse wave analysis showed significant increases in upstroke time (UT) in elderly men compared with young men ( P < 0.05). Multiple regression analysis showed that the UT was correlated with age in all subjects. A significant difference was seen only in the UT between subjects with and without prehypertension. The UT calculated from the retinal blood velocity profile is associated significantly with aging, suggesting that measurement of the UT may detect the changes in the retinal and the systemic vessels with increasing age. The UT is the only parameter that increased significantly in subjects with prehypertension compared with those without prehypertension, suggesting that the UT may indicate the effects of prehypertension on the retinal arterioles.

Correlation between Retina Blood Flow Velocity Assessed by Retinal Function Imager and Retina Thickness Estimated by Scanning Laser Ophthalmoscopy/Optical Coherence Tomography

Purpose: The purpose of this study was to evaluate the correlation between the retinal blood flow (RBF) assessed by the retinal functional imager (RFI) and central macular thickness/volume assessed by a spectral scanning laser ophthalmoscopy/optical coherence tomography (SLO-OCT) system. Methods: Seventeen eyes of 14 consecutive patients with various ocular diseases were examined. Retinal blood circulation characteristics were measured using the RFI. Retinal thickness/volume parameters were obtained by SLO-OCT. Analysis of correlation between RBF velocity and SLO-OCT findings was performed. Results: The analysis of the correlation between RBF and central retinal thickness/volume (5 × 5 mm grid pattern) showed a strong correlation between the average venous RBF velocity and central retinal volume. A linear relationship between the retinal blood velocity in veins and center, middle ring, outer ring and total central squares of macular volume [correlation coefficient 0.86 (p = 0.00001); 0.89 (p = 0.000001); 0.82 (p = 0.0004); 0.85 (p = 0.00001), respectively] has been observed. Arterial blood flow velocity did not correlate with thickness and with central retinal volume. Conclusions: Venous RBF, analyzed by the RFI, significantly correlated with the volume of the central retina, measured by SLO-OCT. Venous blood velocity increased linearly with the increase in the central retinal volume. In this small study, assessment using the RFI provides useful information and may contribute to the further understanding of hemodynamics in the retina blood vessels. The RFI shows promise of being able to analyze retinal hemodynamics noninvasively and may contribute to the further understanding of the relationship between retinal thickening and function.

New insights into ocular blood flow at very high altitudes

Little is known about the ocular and cerebral blood flow during exposure to increasingly hypoxic conditions at high altitudes. There is evidence that an increase in cerebral blood flow resulting from altered autoregulation constitutes a risk factor for acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) by leading to capillary overperfusion and vasogenic cerebral edema. The retina represents the only part of the central nervous system where capillary blood flow is visible and can be measured by noninvasive means. In this study we aimed to gain insights into retinal and choroidal autoregulatory properties during hypoxia and to correlate circulatory changes to symptoms of AMS and clinical signs of HACE. This observational study was performed within the scope of a high-altitude medical research expedition to Mount Muztagh Ata (7,546 m). Twenty seven participants underwent general and ophthalmic examinations up to a maximal height of 6,800 m. Examinations included fundus photography and measurements of retinal and choroidal blood flow, as well as measurement of arterial oxygen saturation and hematocrit. The initial increase in retinal blood velocity was followed by a decrease despite further ascent, whereas choroidal flow increase occurred later, at even higher altitudes. The sum of all adaptational mechanisms resulted in a stable oxygen delivery to the retina and the choroid. Parameters reflecting the retinal circulation and optic disc swelling correlated well with the occurrence of AMS-related symptoms. We demonstrate that sojourns at high altitudes trigger distinct behavior of retinal and choroidal blood flow. Increase in retinal but not in choroidal blood flow correlated with the occurrence of AMS-related symptoms.

Effect of dual endothelin receptor blockade on ocular blood flow in patients with glaucoma and healthy subjects

PURPOSE. Several lines of evidence indicate that altered blood flow regulation may contribute to the pathogenesis of glaucomatous optic neuropathy. Recent data support the hypothesis that the endothelin system is involved in the processes that lead to vascular dysregulation in glaucoma. This study was conducted to test the hypothesis that bosentan, a dual endothelin receptor antagonist, increases ocular blood flow in patients with glaucoma. METHODS. Fourteen patients with primary open-angle glaucoma and 14 sex- and age-matched healthy volunteers were included. Both groups received bosentan 500 mg daily for 8 days. Ocular hemodynamics were assessed at baseline and on the last study day. Retinal vessel diameters and retinal red blood cell velocity were recorded with a retinal vessel analyser and laser Doppler velocimetry, respectively. Choroidal and optic nerve head blood flow were measured with laser Doppler flowmetry. RESULTS. Retinal arteries and veins showed a significant dilatation after administration of bosentan in both groups (5%‐ 8%). Retinal blood velocity and retinal blood flow increased up to 45% after administration of bosentan in both patients and healthy subjects. Administration of bosentan increased choroidal (12%‐17%) and optic nerve head blood flow (11%‐24%) in both groups. The effect of bosentan on ocular blood flow parameters was comparable between the two groups. CONCLUSIONS. The data from the present study indicate that dual inhibition of endothelin receptors increases ocular blood flow in patients with glaucoma and healthy subjects. Further studies are needed to study the dose‐response relationship of this effect and to characterize the role of endothelin receptor subtypes. (Invest Ophthalmol Vis Sci. 2009;50:358‐363) DOI: 10.1167/iovs.08-2460

Retinal arteriolar and capillary vascular reactivity in response to isoxic hypercapnia

The aim of the study was to compare the magnitude of vascular reactivity of the retinal arterioles in terms of percentage change to that of the retinal capillaries using a novel, standardized methodology to provoke isoxic hypercapnia. Ten healthy subjects (mean age 25 years, range 21–31) were recruited. Subjects attended a single visit comprising two study sessions separated by 30 min. Subjects were fitted with a sequential re-breathing circuit connected to a computer-controlled gas blender. Each session consisted of breathing at rest for 10 min (baseline), increase of P ETCO 2 (maximum partial pressure of CO 2 during expiration) by 15% above baseline whilst maintaining isoxia for 20 min, and returning to baseline conditions for 10 min. Retinal hemodynamic measurements were performed using the Canon Laser Blood Flowmeter and the Heidelberg Retina Flowmeter in random order across sessions. Retinal arteriolar diameter, blood velocity and flow increased by 3.3%, 16.9% and 24.9% ( p < 0.001), respectively, during isoxic hypercapnia. There was also an increase of capillary blood flow of 34.8%, 21.6%, 24.9% ( p ≤ 0.006) at the optic nerve head neuroretinal rim, nasal macula and fovea, respectively. The coefficient of repeatability (COR) was 5% of the average P ETCO 2 both at baseline and during isoxic hypercapnia and was 10% and 7% of the average P ETO 2 (minimum partial pressure of oxygen at end exhalation), respectively. The overall magnitude of retinal capillary vascular reactivity was equivalent to the arteriolar vascular reactivity with respect to percentage change of flow. The magnitude of isoxic hypercapnia was repeatable.

Retinal arteriolar vascular reactivity to incremental changes in hyperoxic stimuli during isocapnia

Abstract Purpose To determine the relationship between the magnitude of retinal arteriolar vascular reactivity and incremental changes in hyperoxic stimuli whilst maintaining isocapnia. Methods Twelve healthy, young adults (mean age 27 years, SD 4) participated in a gas protocol consisting of 4 phases at varying fractional expired oxygen levels (FeO2): baseline (15%), hyperoxia I (40%), hyperoxia II (65%), and recovery (15%). End‐tidal carbon dioxide (ETCO2) was maintained at isocapnia throughout the experiment. Retinal arteriolar diameter, blood velocity, and blood flow were assessed non‐invasively using the Canon Laser Blood Flowmeter during each of these phases. Results Repeated measures ANOVA showed that there were significant influences of incremental changes in FeO2 on retinal arteriolar diameter (p&lt;0.0001), blood velocity (p&lt;0.0001), and blood flow (p&lt;0.0001). Paired t‐tests of these retinal hemodynamic parameters during each phase in the gas sequence showed they were significantly different (p&lt;0.05) from each other, with the exception of baseline and recovery values. Incremental increases in FeO2 caused a linear decrease in group mean arteriolar diameter (R2 = 1, p = 0.002), group mean blood velocity (R2 = 0.9968, p = 0.04), and group mean blood flow (R2 = 0.9982, p= 0.03). Conclusion Isocapnic hyperoxia elicits vasoconstriction and the reduction of retinal arteriolar diameter, velocity and blood flow in a dose‐dependent manner over the range of FeO2 explored in this study. Commercial interest

Effect of Dual Endothelin Receptor Blockade on Ocular Blood Flow in Patients with Glaucoma and Healthy Subjects

Several lines of evidence indicate that altered blood flow regulation may contribute to the pathogenesis of glaucomatous optic neuropathy. Recent data support the hypothesis that the endothelin system is involved in the processes that lead to vascular dysregulation in glaucoma. This study was conducted to test the hypothesis that bosentan, a dual endothelin receptor antagonist, increases ocular blood flow in patients with glaucoma. Fourteen patients with primary open-angle glaucoma and 14 sex- and age-matched healthy volunteers were included. Both groups received bosentan 500 mg daily for 8 days. Ocular hemodynamics were assessed at baseline and on the last study day. Retinal vessel diameters and retinal red blood cell velocity were recorded with a retinal vessel analyser and laser Doppler velocimetry, respectively. Choroidal and optic nerve head blood flow were measured with laser Doppler flowmetry. Retinal arteries and veins showed a significant dilatation after administration of bosentan in both groups (+5%-8%). Retinal blood velocity and retinal blood flow increased up to +45% after administration of bosentan in both patients and healthy subjects. Administration of bosentan increased choroidal (+12%-17%) and optic nerve head blood flow (+11%-24%) in both groups. The effect of bosentan on ocular blood flow parameters was comparable between the two groups. The data from the present study indicate that dual inhibition of endothelin receptors increases ocular blood flow in patients with glaucoma and healthy subjects. Further studies are needed to study the dose-response relationship of this effect and to characterize the role of endothelin receptor subtypes.

Effect of Unspecific Inhibition of Cyclooxygenase by Indomethacin on Retinal and Choroidal Blood Flow

Animal studies suggest that retinal and choroidal blood flow decrease after administration of indomethacin, a nonspecific cyclooxygenase inhibitor. Cyclooxygenase is the key enzyme involved in the arachidonic pathway and regulates the production of vasoactive substances such as prostaglandins and thromboxans. The aim of the present study was to investigate the short-term effects of indomethacin on ocular blood flow in healthy humans. A randomized, double-masked, placebo-controlled, two-way crossover study in 12 healthy, male, nonsmoking subjects was performed. Indomethacin was administered as a bolus injection of 0.4 mg/kg followed by continuous infusion of 0.4 mg/kg/h over 120 minutes. Ocular hemodynamic parameters were measured at baseline and up to 3 hours after start of the infusion. Subfoveal choroidal blood flow and fundus pulsation amplitude were measured with laser Doppler flowmetry and laser interferometry, respectively. Retinal vessel diameters were assessed using a retinal vessel analyzer. Retinal blood flow was calculated based on retinal vessel diameters, and red blood cell velocity was measured with laser Doppler velocimetry. Administration of indomethacin decreased retinal arterial diameters up to -4.3% +/- 3.4% and reduced retinal blood velocity by a maximum of -29% +/- 20% (P < 0.05). Calculated retinal blood flow decreased by -27% +/- 21% (P < 0.05), reaching the maximal decrease 60 minutes after administration. Choroidal blood flow and fundus pulsation amplitude (FPA) also decreased during the infusion of indomethacin with maximum effects of -17% +/- 13% (P < 0.05, vs. placebo) and -7% +/- 4% (P < 0.05, vs. placebo), respectively. Results showed a marked decrease in retinal and choroidal blood flow after short-term administration of indomethacin. Whether this decrease can be attributed to a reduced production of prostaglandins or an unknown mechanism has yet to be clarified. Further studies appear to be indicated to investigate whether the long-term intake of indomethacin is associated with an increased risk for vascular eye disease.

Hyperoxia-induced Decrease in Organ Blood Flow

New York Medical College, Valhalla, New York. charles6133@msn.comIn their article regarding the effects of hyperoxia on tissue perfusion, Forkner et al. 1conclusively stated that administration of high oxygen concentration augments tissue oxygenation and produces no adverse effects on tissue oxygenation.Forkner et al. tried to convince readers that Iscoe et al. ’s position2that the hyperventilation induced by hyperoxia as a result of the Haldane effect would lead to arterial hypocapnia and, hence, vasoconstriction in certain vascular beds, including those in brain, is not correct. Based on findings of very old studies, Forkner et al. also argued that during hyperoxia blood flow is not reduced enough to offset the higher oxygen content, and oxygen delivery is enhanced. This argument is not correct. A previous human study has shown that the magnitude of a decrease in cerebral blood flow is much more profound than that of an increase in arterial oxygen content.3In that study, for example, the arterial oxygen content was 18 ml/dl and cerebral blood flow was 54 ml · 100 g−1· min−1(the cerebral oxygen delivery was 9.7 ml · 100 g−1· min−1) at baseline, and after breathing 100% oxygen at 1 atmosphere absolute, the arterial oxygen content increased by 13.4% but the cerebral blood flow decreased by 33%, so the cerebral oxygen delivery decreased to 7.3 ml · 100 g−1· min−1(20.7 ml/dl oxygen content × 36 ml · 100 g−1· min−1), a 25% decrease in cerebral oxygen delivery. In addition, the partial pressure of arterial carbon dioxide decreased by 3 Torr with the administration of 100% oxygen. When hypocapnia was corrected by adding carbon dioxide to 100% oxygen, decreased cerebral blood flow was restored by only 8%. Although the role of hyperoxia-induced hypocapnia on decreases in cerebral blood flow may not be great, the independent cerebral vasoconstrictive effect of hyperoxia is too great in magnitude to be ignored. A hyperoxia-induced decrease in cerebral blood flow would cause a rightward shift of cerebral blood flow-perfusion pressure relationship line, so that cerebral blood flow would be much lower at a given perfusion pressure.By employing laser Doppler velocimetry for the measurement of retinal blood velocity and fundus imaging with the Zeiss retinal vessel analyzer for the assessment of retinal vessel diameter, another previous human study4showed that hyperoxia by breathing greater than 92% oxygen decreases retinal blood velocity and retinal blood flow by 60% each and decreases retinal vessel diameter by 15%, suggesting that the decrease in retinal blood flow is mainly the result of decreased cerebral blood flow rather than the retinal vessel vasoconstriction. The decrease in retinal blood flow during hyperoxia could contribute to ischemic retinopathy when combined with increased intraocular pressure5during prone spine surgery.A clinical study has shown that breathing 100% oxygen reduces coronary blood flow velocity by 20% and increases coronary vascular resistance by 23% in patients with coronary artery disease and that vitamin C reverses this effect, suggesting that these changes are mediated by an oxidative stressor acting on the coronary microcirculation.6A hyperoxia-induced decrease in coronary microcirculatory blood flow in patients with coronary artery stenosis can be detrimental.To determine whether the routine use of high inspired oxygen concentration during the perioperative period alters the incidence of surgical site infection in a general surgical population, a double-blind, randomized controlled trial was conducted.7The incidence of surgical site infection was significantly higher (25%) in the group receiving inspired oxygen concentration of 80% than in the group with inspired oxygen concentration of 35% (11.3%). This is further evidence that does not support the argument of Forkner et al. Supplemental oxygen benefits patients who would otherwise suffer hypoxia while breathing room air. However, in this situation, supplemental oxygen would not induce hyperoxia. Forkner et al. made no distinction between supplemental oxygenation and the administration of high oxygen concentration.The effect of hyperoxia-induced hypocapnia on decreases in cerebral blood flow or other organ flow may not be great and is unlikely to be of clinical significance. However, the independent vasoconstricitive effect of hyperoxia is too great in magnitude to be ignored. One cannot say that hyperoxia is harmless.New York Medical College, Valhalla, New York. charles6133@msn.com

Effects of moxaverine and placebo on ocular blood flow

Abstract Purpose: A number of eye diseases are associated with perfusion abnormalities. Moxaverine, because of its known direct vasodilator effect, is used in the therapy of perfusion abnormalities in the brain, the heart and the extremities. The present study aimed to investigate whether moxaverine affects ocular blood flow. Methods: 16 healthy volunteers were studied in this randomized, double masked, placebo‐controlled twoway crossover study. Moxaverine (Ursapharm, Saarbrücken, Germany, 150mg) was administered intravenously over 30 minutes. Ocular hemodynamic parameters were measured before and up to 90 minutes after drug administration. Retinal arterial and venous diameters were measured with a Retinal Vessel Analyzer. Retinal blood velocity (RBV) was assessed with laser Doppler velocimetry, choroidal (CF) and optic nerve head blood flow (ONF) were measured with laser Doppler flowmetry. Results: RBV and ONF tended to increase by 13.6±13.3% and 11.8±12.7% respectively after administration of moxaverine, but this effect was not significant versus placebo. Moxaverine increased significantly CF by 22.6±27.9%. In retinal veins moxaverine induced vasodilation (2.6±2.8%), but this effect was not significant versus placebo. Retinal blood flow increased after infusion of moxaverine (19.6±16.5%), but again this effect did not reach the level of significance most likely due to the small numbers of subjects. Conclusions: The present study indicates an increase in ocular blood flow after systemic infusion of a single dose of moxaverine in healthy subject. Further studies are warranted to investigate whether this effect can also be seen after repeated dose treatment in patients with ocular vascular disease.

Concentration-dependent vasoconstrictive effect of hyperoxia on hypercarbia-dilated retinal arterioles

Background/aims The relative effects of simultaneously administered oxygen and carbon dioxide on vascular resistance are unknown. The purpose of the study was to investigate the independent effect of oxygen partial pressure on hypercarbia-induced vasodilation in the retinal arterioles. Methods Twelve young healthy volunteers participated in the study. End-tidal partial pressure of carbon dioxide was raised 23% from the baseline (i.e. air) at normoxia and then maintained constant while end-tidal partial pressure of oxygen (P etO 2) was raised in a stepwise incremental fashion. Retinal vessel diameter and blood velocity were measured in the superior-temporal arteriole using the Canon Laser Blood Flowmeter. Results Hypercarbia resulted in a 16% increase in blood velocity and a 22% increase in blood flow ( p < 0.05). At maximal hyperoxia (group mean P etO 2 of 556 mm Hg) vessel diameter, blood velocity and flow were reduced by 9%, 22% and 36%, respectively, relative to baseline ( p < 0.001). Conclusion The concentration-dependent vasoconstrictive effect of oxygen in retinal arterioles was quantified for the first time by implementing precise control of end-tidal concentrations of CO 2 and O 2. Oxygen-induced vasoconstriction is sufficiently potent to offset and reverse hypercarbia-induced vasodilation.

Retinal Arteriolar Diameter, Blood Velocity, and Blood Flow Response to an Isocapnic Hyperoxic Provocation in Early Sight-Threatening Diabetic Retinopathy

To quantify the magnitude of retinal arteriolar vascular reactivity in diabetic patients stratified by severity of retinopathy and in age-matched control subjects. The sample comprised 21 nondiabetic control subjects (group 1), 19 patients with no clinically visible DR (group 2), 19 patients with mild-to-moderate nonproliferative DR and without clinically evident diabetic macular edema (DME) (group 3), and 17 patients with DME (group 4). methods Subjects initially breathed air, followed by oxygen, while isocapnia was maintained. Retinal arteriolar diameter and blood velocity measurements were acquired simultaneously. Changes in blood velocity and wall shear rate (WSR) were significantly less in groups 3 and 4 (P < 0.0001 and P = 0.0002, respectively) than in groups 1 and 2. Change in blood flow was significantly less in group 4 (P < 0.004) than in groups 1 and 2. The change in maximum-to-minimum (max:min) ratio was significantly less in groups 2 and 4 than in group 1 (P = 0.001). There was a significant relationship between baseline objective edema indices and vascular reactivity. The magnitude of vascular reactivity in response to isocapnic hyperoxia was reduced in those individuals with clinically evident DR relative to subjects without diabetes. The differences in vascular reactivity occurred in the absence of any difference in baseline hemodynamic values. Vascular reactivity is impaired in early sight-threatening DR, and this impairment is related to the objectively defined magnitude of retinal edema.

Comparison of retinal arteriolar and venular variability in healthy subjects

Study of retinal autoregulation is important because vascular dysfunction is a precursor of many retinal diseases. Previous research has focused on venular blood flow because the minimal venular pulsatility was thought to provide more reproducible results. This study compared the variability of arteriolar and venular blood flow measurements in response to isocapnic hyperoxia, a provocation known to constrict blood vessels and reduce blood velocity. Data was collected using a non-invasive laser Doppler instrument that permitted the simultaneous measurement of retinal blood velocity and vessel diameter, allowing the derivation of blood flow. Measurements were collected from 20 young subjects before, during and after exposure to hyperoxia. Isocapnia was maintained throughout hyperoxia using a previously validated sequential re-breathing circuit. Arteriolar and venular diameters decreased during hyperoxia by 8.7% ( p = 0.0001) and 14.2% ( p = 0.0001), respectively. Hyperoxia caused significant decreases in arteriolar and venular blood velocity (31.2%, p = 0.0001 and 18.0%, p = 0.0001, respectively) and flow (43.2%, p = 0.0001 and 40.0%, p = 0.0002, respectively). The coefficients of variation for intra-individual measurements of diameter, velocity and flow were comparable in magnitude between the two vessel types. Measures of arteriolar pulsatility, such as Pulsatility ratio, Resistivity ratio and Pulsatility index, increased significantly during hyperoxia, indicating increased downstream vascular resistance. We conclude that retinal arterioles and venules provide equally reproducible results for autoregulation studies and that arteriolar pulsatility profiles provide additional useful information regarding vascular resistance.

Error in Figure in: Effect of P2X7 Receptor Activation on the Retinal Blood Velocity of Diabetic Rabbits

Error in Figure in: Effect of P2X7 Receptor Activation on the Retinal Blood Velocity of Diabetic Rabbits

Novel methodology to comprehensively assess retinal arteriolar vascular reactivity to hypercapnia

Purpose (1) Describe a new methodology that permits the comprehensive assessment of retinal arteriolar vascular reactivity in response to a sustained and stable hypercapnic stimulus. (2) Determine the magnitude of the vascular reactivity response of the retinal arterioles to hypercapnic provocation in healthy, young subjects. Methodology Eleven healthy subjects of mean age 27 years (SD 3.43) participated in the study and one eye was randomly selected. A mask attached to a sequential rebreathing circuit, and connected to a gas delivery system, was fitted to the face. To establish baseline values, subjects breathed bottled air for 15 min and at least 6 blood flow measurements of the supero-temporal arteriole were acquired using the Canon Laser Blood Flowmeter (CLBF). Air flow was then decreased until a stable increase in fractional end-tidal CO 2 concentration (F ETCO 2) of 10–15% was achieved. CLBF measurements were acquired every minute (minimum of 6 measurements) during the 20-minute period of elevated F ETCO 2. F et CO 2 was then reduced to baseline levels, and 6 further CLBF measurements were acquired. Respiratory rate, blood pressure, pulse rate and oxygen saturation were monitored continuously. Results Retinal arteriolar diameter, blood velocity and blood flow increased during hypercapnia relative to baseline ( p = 0.0045, p < 0.0001 and p < 0.0001, respectively). Group mean F ETCO 2 showed an increase of 12.0% (SD 3.6) relative to baseline ( p < 0.0001). Conclusions This study describes a new methodology that permits the comprehensive assessment of retinal arteriolar vascular reactivity in response to a sustained and stable hypercapnic stimulus. Retinal arteriolar diameter, blood velocity and blood flow increased significantly in response to a hypercapnic provocation in young, healthy subjects.

Effect of P2X7 Receptor Activation on the Retinal Blood Velocity of Diabetic Rabbits

To test the effect of activation of P2X7 receptors on retinal blood velocity in diabetic rabbits. Immunohistochemical analysis was performed on healthy and diabetic rabbit eyes using P2X7 receptor antibodies. Diabetes was induced using alloxan. Retinal blood velocity was measured with the laser speckle circulation analyzer. Visual function was assessed using electroretinography. Cells in inner retinal layers were positive for anti-P2X7 receptor antibodies in healthy rabbits. The distribution of positive cells extended to outer layers and some small vessels stained in diabetic rabbits. When assayed 24 hours after an intravitreal injection of 150 nmol of benzoylbenzoyl adenosine triphosphate (BzATP), a P2X7 agonist, the retinal blood velocity in healthy rabbits was reduced by approximately 30%; this reduction continued for at least 4 weeks. Only in diabetic rabbits did an injection of 50 nmol of BzATP reduce retinal blood velocity by approximately 30% and the amplitudes of electroretinography a waves, b waves, and oscillatory potentials for at least 4 weeks. Soon after the onset of alloxan-induced diabetes, retinal blood velocity and function become more vulnerable to reduction initiated through P2X7 receptors. Our findings support the hypothesis that the retinal circulation disorder accelerated by activation of P2X7 receptors may be involved in the early changes of diabetic retinopathy.

Intravenous Administration of Diphenhydramine Reduces Histamine-Induced Vasodilator Effects in the Retina and Choroid

Intravenous administration of histamine causes an increase in choroidal blood flow (ChBF) and retinal vessel diameters in healthy subjects. The receptor mediating this response has not yet been identified. The present study was undertaken to clarify whether H1 receptor blockade with diphenhydramine affects the hemodynamic response of histamine in the choroid and the retina. A randomized, double-masked, placebo-controlled, two-way crossover study was performed in 18 healthy, male, nonsmoking subjects. Histamine (0.32 microg/kg per minute over 30 minutes) was infused intravenously in the absence (NaCl as placebo) or presence of the H1 blocker diphenhydramine (1.0 mg/min over 50 minutes). Ocular hemodynamic parameters, blood pressure, and intraocular pressure were measured before drug administration, after infusion of diphenhydramine or placebo, and after co-infusion of histamine. Subfoveal ChBF and fundus pulsation amplitude (FPA) were measured with laser Doppler flowmetry and laser interferometry, respectively. Retinal arterial and venous diameters were measured with a retinal vessel analyzer. Retinal blood velocity was assessed with bidirectional laser Doppler velocimetry. Administration of histamine caused a decrease in mean arterial pressure by -4% +/- 9% (ANOVA P = 0.01). This effect was blunted by coadministration of diphenhydramine (ANOVA, P = 0.04). Histamine significantly increased FPA and subfoveal ChBF. Coadministration of diphenhydramine significantly reduced this effect (ANOVA; FPA P = 0.001, ChBF P = 0.049). Histamine significantly increased retinal arterial diameter by +3.5% +/- 4.5% and retinal venous diameter by +3.7% +/- 2.8%. Again, coadministration of diphenhydramine significantly reduced the vasodilative effect to +0.3% +/- 5.5% in retinal arteries (ANOVA, P = 0.00006) and to +0.9% +/- 2.5% in retinal veins (ANOVA, P = 0.004). The present data confirm that histamine increases ChBF and retinal vessel diameters in healthy subjects. Administration of the H1 receptor blocker diphenhydramine significantly reduced histamine-induced changes in ocular perfusion parameters. These results strongly indicate that in the retina and choroid, H1 receptors are involved in the histamine-mediated hemodynamic effects in vivo.

Effect of histamine and cimetidine on retinal and choroidal blood flow in humans

Intravenous administration of histamine causes an increase in choroidal blood flow and retinal vessel diameter in healthy subjects. The mechanism underlying this effect remains to be elucidated. In the present study, we hypothesized that H2 receptor blockade alters hemodynamic effects of histamine in the choroid and retina. Eighteen healthy male nonsmoking volunteers were included in this randomized, double-masked, placebo-controlled two-way crossover study. Histamine (0.32 microg.kg(-1).min(-1) over 30 min) was infused intravenously in the absence (NaCl as placebo) or presence of the H2 blocker cimetidine (2.3 mg/min over 50 min). Ocular hemodynamic parameters, blood pressure, and intraocular pressure were measured before drug administration, after infusion of cimetidine or placebo, and after coinfusion of histamine. Subfoveal choroidal blood flow and fundus pulsation amplitude were measured with laser-Doppler flowmetry and laser interferometry, respectively. Retinal arterial and venous diameters were measured with a retinal vessel analyzer. Retinal blood velocity was assessed with bidirectional laser-Doppler velocimetry. Histamine increased subfoveal choroidal blood flow (+14 +/- 15%, P < 0.001), fundus pulsation amplitude (+11 +/- 5%, P < 0.001), retinal venous diameter (+3.0 +/- 3.6%, P = 0.002), and retinal arterial diameter (+2.8 +/- 4.2%, P < 0.01) but did not change retinal blood velocity. The H2 antagonist cimetidine had no significant effect on ocular hemodynamic parameters. In addition, cimetidine did not modify effects of histamine on choroidal blood flow, fundus pulsation amplitude, retinal venous diameter, and retinal arterial diameter compared with placebo. The present data confirm that histamine increases choroidal blood flow and retinal vessel diameters in healthy subjects. This ocular vasodilator effect of histamine is, however, not altered by administration of an H2 blocker. Whether the increase in blood flow is mediated via H1 receptors or other hitherto unidentified mechanisms remains to be elucidated.