Biomedical subjects

Guido T Dorner

Publications and source records attributed to Guido T Dorner.

11 recordsLinked to original sources

PubMed2003

The ocular hemodynamic response to nitric oxide synthase inhibition is unaltered in patients with early type I diabetes.

BACKGROUND: An impaired ocular hemodynamic response to systemic nitric oxide synthesis inhibition has been demonstrated in patients with long-standing insulin-dependent diabetes mellitus. It is unclear whether this altered responsiveness is already detectable in early uncomplicated type I diabetes. METHODS: The effect of the nitric oxide synthase inhibitor N(G)-monomethyl- l-arginine (L-NMMA) was studied in 10 male patients with early type I diabetes under euglycemic conditions and 10 healthy matched control subjects in a single (analyst) blinded cohort study design. Changes in ocular hemodynamics (fundus pulsation amplitude, mean flow velocity in the ophthalmic artery) and in pulse rate and mean blood pressure were measured in response to systemic intravenous doses of 1.5, 3, and 6 mg/kg L-NMMA. RESULTS: L-NMMA dose-dependently and significantly decreased fundus pulsation amplitude (-21.0% vs -23.3% in diabetics and controls, respectively), mean flow velocity in the ophthalmic artery (-12.3% vs -10.8%) and pulse rate (-15.4% vs -16.6%) and increased mean arterial pressure (+19.5% vs +14.7%). The ocular and systemic hemodynamic effects of L-NMMA were not different between patients with diabetes and controls. CONCLUSION: The responsiveness of the choroidal vasculature and the ophthalmic artery to L-NMMA is not altered in early type 1 diabetes. An impaired hemodynamic response to nitric oxide synthesis inhibition in diabetes is therefore not caused by a primary defect but rather due to altered vascular responsiveness secondary to long-standing disease.

Adult↗

PubMed2003

Nitric oxide regulates retinal vascular tone in humans.

The purpose of the present study was to investigate the contribution of basal nitric oxide (NO) on retinal vascular tone in humans. In addition, we set out to elucidate the role of NO in flicker-induced retinal vasodilation in humans. Twelve healthy young subjects were studied in a three-way crossover design. Subjects received an intravenous infusion of either placebo or NG-monomethyl-L-arginine (L-NMMA; 3 or 6 mg/kg over 5 min), an inhibitor of NO synthase. Thereafter, diffuse luminance flicker was consecutively performed for 16, 32, and 64 s at a frequency of 8 Hz. The effect of L-NMMA on retinal arterial and venous diameter was assessed under resting conditions and during the hyperemic flicker response. Retinal vessel diameter was measured with a Zeiss retinal vessel analyzer. L-NMMA significantly reduced arterial diameter (3 mg/kg: -2%; 6 mg/kg: -4%, P < 0.001) and venous diameter (3 mg/kg: -5%; 6 mg/kg: -8%, P < 0.001). After placebo infusion, flicker induced a significant increase in retinal vessel diameter (P < 0.001). At a flicker duration of 64 s, arterial diameter increased by 4% and venous diameter increased by 3%. L-NMMA did not abolish these hyperemic responses but blunted venous vasodilation (P = 0.017) and arterial vasodilation (P = 0.02) in response to flicker stimulation. Our data indicate that NO contributes to basal retinal vascular tone in humans. In addition, NO appears to play a role in flicker-induced vasodilation of the human retinal vasculature.

Adult↗

PubMed2003

Ocular surface changes and tear film alterations associated with sun gazing during a solar eclipse.

PURPOSE: A solar eclipse occurred in central Europe on August 11th, 1999. Following the eclipse, patients with ocular symptoms were investigated. Gazing at the sun without protection is liable to damage the retina. Our attention was focused on changes of the ocular surface and the tear film. METHODS: Forty-three patients were investigated within one week after the solar eclipse as baseline. 33 of them were followed up one year later. Visual acuity and the central visual-field were measured, and the ocular surface and the fundus were examined using a slit lamp. The quality of the lacrimal tear film was examined using Schirmer's test for the aqueous layer, break-up time for the mucous layer and interference observation for the lipid layer, measured by a slit lamp and a tearoscope. RESULTS: At the baseline 19 patients had non-specific visual problems. Pathological alterations of the tear film were seen in all three tear-film layers: Schirmer's test was pathological in 87%, break-up time decreased in 85%, the interference pattern of the lipid layer changed in 67% and there were changes in 87% using the tearoscope. One year later the non specific visual disorders had disappeared. Schirmer's test did not reveal much change from the baseline: 51% pathological, 24% remained pathological in break-up-time and the lipid layer was normalized except in 9%. Using the tearoscope, lipids were better than grade 3 in all patients. CONCLUSION: After gazing at a solar eclipse the ocular surface and tear film changed. While the aqueous layer remained pathological in many patients, the lipid layer and the mucous layer recovered spontaneously.

Adult↗

PubMed2003

Hyperglycemia affects flicker-induced vasodilation in the retina of healthy subjects.

Flickering light stimulation of retinal photoreceptors induces retinal vessel dilation in humans. In the present study the effect of high blood glucose levels on this neuro-vascular mechanism was investigated in 12 healthy young male subjects. Blood glucose levels were consecutively increased during 30 min to 100, 200 and 300 mg/dl and kept at the respective level for the following 30 min using hyperglycemic insulin clamps. Eight Hertz flickering light was applied to the fundus at the end of each glucose plateau during continuous retinal vessel diameter measurements with the Zeiss retinal vessel analyser (RVA). During normoglycemia (100 mg/dl) flickering light induced a significant vasodilation of retinal arteries (+2.8+/-0.4%, p<0.0001) and veins (+2.6+/-0.4%, p<0.0001). At 300 mg/dl blood glucose the flicker response in retinal veins was significantly decreased by 55% (p=0.015 versus 100 mg/dl). The modified RVA employed in the present study provides high sensitivity and is capable of studying flicker-induced retinal vasodilation. Using this technique the present study confirms that flickering light stimulation of the human retina induces vasodilation in retinal vessels in healthy subjects. In addition, our data indicate that the retinal vessel response to flickering light stimulation is significantly reduced during hyperglycemia in humans. The relevance of this finding for diabetes-related eye disease remains to be shown.

Adult↗

PubMed2003

Levels of adhesion molecules do not decrease after 3 months of statin therapy in moderate hypercholesterolaemia.

Studies in animals and humans indicate a pivotal role for adhesion molecules (AMs) in the pathogenesis of atherosclerosis. Whereas an association between hypercholesterolaemia and AM expression has been suggested, it is unclear whether lowering cholesterol decreases AM expression and release. We compared the effects of a 3-month treatment with standard doses of three different statins (atorvastatin, simvastatin and pravastatin) on plasma levels of circulating AM (cAM) in 75 hypercholesterolaemic patients in a randomized clinical trial. Plasma levels of circulating (c)E-selectin, circulating intercellular adhesion molecule-1 (cICAM-1) and circulating vascular cell adhesion molecule-1 (cVCAM-1) were measured before and after 3 months of therapy. None of the statins lowered plasma cAM levels and pooled analyses of all patients showed a 1.7% [95% confidence interval (CI), -1.4-4.9%] increase in cE-selectin, a 2.1% (95% CI, -0.2-4.4%) increase in cICAM-1, and a 2.7% (95% CI, -0.6-6.1%) increase in cVCAM-1 levels. cAM levels did not decrease, even in patients with a >50% decrease ( n =19) in low-density lipoprotein cholesterol levels. This study provides strong evidence that 3 months of therapy with three different statins does not decrease cAM levels, despite normalization of cholesterol levels, and a minor decrease in C-reactive protein levels in patients with moderate hypercholesterolaemia.

Adult↗

PubMed2003

Effects of adrenomedullin on ocular hemodynamic parameters in the choroid and the ophthalmic artery.

PURPOSE: Adrenomedullin acts as a vasodilator and may play a role in inflammatory processes in the eye. This study was designed to determine whether nitric oxide formation is involved in the response to adrenomedullin in the ocular vasculature in vivo. METHODS: The effects of systemic intravenous adrenomedullin (3.2-16.0 pmol/[kg. min])) on choroidal blood flow were assessed by measurement of fundus pulsation amplitude and laser Doppler flow in the macula, and on blood flow in the ophthalmic artery by ultrasound Doppler flow in pilot studies (n = 7). Subsequently, in a double-blind randomized placebo-controlled crossover study in eight healthy male subjects the effects of 12.8 pmol/(kg. min) adrenomedullin on ocular and systemic hemodynamics were investigated. Adrenomedullin was co-infused with the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (3 mg/kg bolus and 30 micro g/[kg. min] continuous intravenous infusion) or vehicle control on separate study days. RESULTS: Adrenomedullin dose dependently increased choroidal blood flow and flow velocity in the ophthalmic artery. N(G)-monomethyl-L-arginine reduced the effect of adrenomedullin on fundus pulsation amplitude, but did not alter the flow response in the ophthalmic artery. Systemic hemodynamics were unaffected by adrenomedullin infusion. CONCLUSIONS: Ocular blood flow is sensitive to changes in adrenomedullin concentrations. The acute vasodilator effects of adrenomedullin are nitric oxide-dependent in the choroid, but not in the ophthalmic artery.

Adrenomedullin↗

PubMed2003

Effect of intravenous administration of sodium-lactate on retinal blood flow in healthy subjects.

PURPOSE: The present study was designed to investigate the effect of intravenously administered sodium lactate on ocular blood flow. METHODS: Twelve healthy male volunteers received either sodium lactate (0.6 mol/L) or physiologic saline solution in a randomized, double-masked, two-way crossover study. Sodium lactate or placebo were administered at an infusion speed of 500 and 1000 mL/h for 30 minutes each. Blood flow measurements were performed in the last 10 minutes of the infusion periods. Retinal blood flow was calculated based on the measurement of maximum erythrocyte velocity, assessed with bidirectional laser Doppler velocimetry, and retinal vessel diameter obtained with a retinal vessel analyzer. Choroidal blood flow was assessed with laser Doppler flowmetry and laser interferometric measurement of fundus pulsation amplitude. RESULTS: Administration of lactate increased blood lactate concentration from 1.3 +/- 0.4 to 3.9 +/- 0.7 mmol/L (P < 0.001) and to 7.1 +/- 1.4 mmol/L (P < 0.001) at infusion speeds of 500 and 1000 mL/h, respectively. At these blood lactate concentrations, retinal blood flow increased by 15% +/- 20% and by 24% +/- 37% (ANOVA, P = 0.01). Fundus pulsation amplitude increased by 3% +/- 6% and 10% +/- 5% (ANOVA, P = 0.04) at the two plasma lactate concentrations. Subfoveal choroidal blood flow measured with laser Doppler flowmetry tended to increase by 10% +/- 15% and 13% +/- 20% (ANOVA, P = 0.19), but this effect was not significant. Infusion of sodium lactate induced alkalosis in arterial blood taken from the earlobe (7.41 +/- 0.03 at baseline; 7.50 +/- 0.03 during lactate infusion; P = 0.001). CONCLUSIONS: The data indicate that intravenously administered sodium lactate increases retinal blood flow. Whether this is related to a cytosolic redox impairment or to other hitherto unidentified mechanism remains to be clarified. Further studies are needed to determine whether lactate plays a role in regulation of choroidal blood flow.

Alkalosis↗

PubMed2002

Effects of dopamine on human retinal vessel diameter and its modulation during flicker stimulation.

We performed a randomized, subject-blinded, placebo and time-controlled, two-way crossover study in 12 healthy male subjects. Placebo or dopamine was administered on two separate study days. After saline infusion, dopamine hydrochloride was infused in three consecutive doses (5, 10, and 15 microg x kg(-1) x min(-1)). Plasma levels of dopamine were determined at each perfusion step. Arterial and venous retinal vessel diameters were measured with the use of a Zeiss retinal vessel analyzer. Diffuse luminance flicker stimuli of 8 Hz were applied for 60 s. Blood pressure and pulse rate were monitored continuously. Flicker stimulation (8 Hz) increased retinal vessel diameters under basal conditions. The response to 8-Hz flicker light was significantly reduced by dopamine administration. In addition, dopamine slightly but significantly increased retinal vessel diameters. Dopamine hydrochloride significantly increased systolic but not diastolic or mean arterial pressure. The present study indicates that dopamine has a distinct effect on retinal vessel diameters also attenuating the flicker-induced response reactivity of retinal vessels. This implies a role of dopamine in retinal blood flow hemodynamics.

Adult↗

PubMed2002

Effect of noradrenaline on retinal blood flow in healthy subjects.

PURPOSE: To gain insight into the role of circulating catecholamines on retinal blood flow in vivo. DESIGN: Nonrandomized, open, crossover design. PARTICIPANTS: In 10 healthy male subjects, tyramine and noradrenaline were administered in stepwise increasing doses. These doses were selected to induce comparable changes in systemic blood pressure. METHODS: During each infusion step, retinal vessel diameter and retinal venous blood speed were measured with the Zeiss retinal vessel analyzer (Zeiss, Jena, Germany) and laser Doppler velocimetry, respectively. MAIN OUTCOME MEASURES: Retinal blood flow through a major temporal vein was calculated. RESULTS: As expected, tyramine and noradrenaline induced a systemic hypertensive response. Tyramine caused a moderate increase in noradrenaline plasma levels, whereas exogenous noradrenaline increased noradrenaline plasma levels more than 10-fold. Nevertheless, neither tyramine nor noradrenaline induced any effect on retinal hemodynamic parameters. CONCLUSIONS: These data indicate that even high levels of circulating noradrenaline have little impact on retinal vascular tone and retinal blood flow. Hence, the adrenergic system appears not to play a major role in retinal blood flow regulation.

Adrenergic Uptake Inhibitors↗

PubMed2002

Calculation of the diameter of the central retinal artery from noninvasive measurements in humans.

PURPOSE: The aim of the present study was to calculate the diameter of the central retinal artery from results as obtained with non-invasive techniques in healthy young subjects. METHODS: Twenty-four healthy male subjects participated in this study. Total retinal blood flow was calculated from combined bi-directional laser Doppler velocimetry and measurement of retinal venous diameters using the Zeiss retinal vessel analyzer. Using these techniques red blood cell velocity and vessel diameters of all visible veins entering the optic nerve head were measured and total retinal blood flow was calculated. Blood flow velocity in the central retinal artery was measured with color Doppler imaging. Form these outcome parameters the diameter of the central retinal artery was calculated for each subject individually. RESULTS: In the present study cohort the mean retinal blood flow was 38.1 +/- 9.1 microl/min and the mean flow velocity in the central retinal artery was 6.3 +/- 1.2 cm/s. From these data we calculated a mean diameter of the central retinal artery of 163 +/- 17 microm. CONCLUSIONS: Our results are in good agreement with data obtained from in vitro studies. The data of the present study also indicate that one needs to be careful to interpret velocity data from the central retinal artery in terms of retinal blood flow.

Adult↗

PubMedDate not supplied

Changing antiglaucoma therapy from timolol to betaxolol: effect on ocular blood flow.

The aim of the present study was to investigate the effect of a therapy change from timolol to betaxolol on ocular blood flow in patients with open-angle glaucoma. This randomized double-blind study comprised 34 consecutive patients with open-angle glaucoma, already treated with either timolol alone or in combination with other antiglaucoma agents. The patients were randomly allocated to receive either betaxolol (n = 17) or timolol (n = 17) instead of the present timolol drops. Additional antiglaucoma therapy remained unchanged. The retinal blood flow was assessed by scanning laser Doppler flowmetry and the pulsatile choroidal blood flow was assessed by laser interferometric measurement of fundus pulsation amplitude. Ocular blood flow measurement as well as systemic hemodynamic and intraocular pressure (IOP) measurements were performed at baseline and 1 week and 1 and 3 months after the therapy change. Visual field testing was performed at baseline and at 3 months. After 3 months of treatment with either timolol or betaxolol, neither the retinal nor the pulsatile choroidal blood flow were significantly altered. The power to detect a 9% change in pulsatile choroidal blood flow and a 20% change in retinal blood flow in the present study was 90%. The IOP was not significantly altered in either group. In contrast, visual fields slightly improved after betaxolol treatment compared to baseline (p = 0.047), but this effect was not significant versus timolol. Changing therapy from timolol to betaxolol has no effect on ocular blood flow in patients with open-angle glaucoma.

Adolescent↗