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Biomedical subjects

Gabriele Fuchsjäger-Mayrl

Publications and source records attributed to Gabriele Fuchsjäger-Mayrl.

13 recordsLinked to original sources
PubMed2004

Ocular blood flow and systemic blood pressure in patients with primary open-angle glaucoma and ocular hypertension.

PURPOSE: There is evidence that altered optic nerve head (ONH) blood flow may play a role in the development and progression of glaucoma. In the present study, the baseline characteristics were examined in a study population participating in a clinical trial in which the ocular hemodynamic effects of timolol and dorzolamide were compared. METHODS: One hundred forty patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT) were included in this trial and their baseline parameters compared with those of a group of 102 age-matched control subjects. Scanning laser Doppler flowmetry was used to measure blood flow in the temporal neuroretinal rim and the cup of the ONH. Pulsatile choroidal blood flow was assessed by laser interferometric measurement of fundus pulsation amplitude. In addition, hemodynamic parameters and mean arterial pressure were calculated in both groups. RESULTS: All ocular hemodynamic parameters were significantly lower in the POAG/OHT group compared with the healthy control group (P < 0.001 each). In addition, a significant positive correlation between laser Doppler flowmetry readings and mean arterial pressure was observed in patients with glaucoma but not in healthy control subjects. Likewise, the correlation coefficient between fundus pulsation amplitude and mean arterial pressure was higher in patients with glaucoma than in healthy control subjects. CONCLUSIONS: The present study indicates reduced ONH and choroidal blood flow and an abnormal association between blood pressure and ocular perfusion in patients with primary open-angle glaucoma or ocular hypertension, independent of topical antiglaucoma medication. Hence, vascular dysregulation appears to be an early manifestation in glaucoma that is not caused by pharmacologic intervention.

Antihypertensive Agents↗
PubMed2003

Propranolol and atropine do not alter choroidal blood flow regulation during isometric exercise in healthy humans.

Recent studies indicate that the human choroid has a considerable capacity to keep blood flow constant despite exercise-induced increases in perfusion pressure. The mechanisms underlying this vasoconstrictor response remain unclear. We hypothesized that pharmacological modulation of the autonomic nervous system may alter the choroidal pressure/flow relationship during squatting. To test this hypothesis, we performed a randomized, double-masked, placebo-controlled, three-way crossover study in 15 healthy male volunteers. Subjects received, on different study days, intravenous infusions of the beta-adrenoceptor antagonist propranolol, the muscarinic receptor antagonist atropine, or placebo. During these infusions, subjects performed squatting for 6 min. Choroidal blood flow was assessed with laser Doppler flowmetry and ocular perfusion pressure (OPP) was calculated from mean arterial pressure and intraocular pressure. As expected, propranolol reduced basal pulse rate, whereas atropine increased pulse rate, indicating that the drugs were administered at systemically effective doses. None of the drugs altered the choroidal pressure/flow relationship during isometric exercise. These data indicate that the regulatory vasoconstrictor capacity of the choroid during exercise is not affected by systemic blockade of beta-adrenoceptors or muscarinic receptors.

Adrenergic beta-Antagonists↗
PubMed2003

Changes in choroidal blood flow during light/dark transitions are not altered by atropine or propranolol in healthy subjects.

It has recently been reported that light/dark transitions lead to changes in choroidal blood flow. Several observations indicate that these changes in choroidal perfusion are triggered at least in part by neural mechanisms. In the present study we hypothesised that the choroidal blood flow response to changes in retinal illumination may be modified by either the muscarinic receptor antagonist atropine or by the beta-receptor antagonist propranolol. In 15 healthy subjects the response of choroidal perfusion was studied in a randomised placebo-controlled three way cross-over study using laser Doppler flowmetry and laser interferometric measurement of fundus pulsation amplitude. Before drug administration a transition from light to dark reduced both choroidal haemodynamic parameters by 8%-12%. Neither propranolol nor atropine altered basal choroidal blood flow or choroidal blood flow responses to light/dark transitions. Our data indicate that neither muscarinic nor beta-receptors are involved in the choroidal blood flow response to changes in retinal illumination. Further studies are required to elucidate which mechanisms contribute to this blood flow behaviour of the choroid.

Adaptation, Ocular↗
PubMed2003

Role of NO in choroidal blood flow regulation during isometric exercise in healthy humans.

PURPOSE: Nitric oxide (NO) is an important regulator of basal choroidal blood flow. Animal experiments indicate that NO is also involved in choroidal blood flow regulation during changes in ocular perfusion pressure and inhibition of NO synthase (NOS) has been reported to shift choroidal pressure-flow curves to the right. The hypothesis for the study was that inhibition of NOS may influence choroidal blood flow during isometric exercise. METHODS: To test this hypothesis, a randomized, double-masked, placebo-controlled, three-way crossover study was performed in 12 healthy male volunteers. Subjects received on different study days intravenous infusions of N(G)-monomethyl-L-arginine (L-NMMA), phenylephrine, or placebo. During these infusion periods, subjects were asked to squat for 6 minutes. Choroidal blood flow was assessed with laser Doppler flowmetry, and ocular perfusion pressure (OPP) was calculated from mean arterial pressure and intraocular pressure. RESULTS: L-NMMA and phenylephrine increased resting OPP by 10% and 13%, respectively, but only L-NMMA reduced resting choroidal blood flow (-17%, P < 0.001). The relative increase in OPP during isometric exercise was comparable with all drugs administered. Isometric exercise increased choroidal blood flow during administration of placebo and phenylephrine, but not during administration of L-NMMA (P < 0.001 vs. placebo). CONCLUSIONS: These data indicate that NO plays an important role in the regulation of choroidal blood flow during isometric exercise.

Adult↗
PubMed2003

Role of endothelin-1 in choroidal blood flow regulation during isometric exercise in healthy humans.

PURPOSE: There is evidence that the choroid has some autoregulatory capacity in response to changes in ocular perfusion pressure (OPP). The mediators of this response are hitherto unidentified. The hypothesis for the current study was that endothelin (ET)-1 and/or angiotensin (ANF)-II may be involved in choroidal vasoconstriction during an increase in OPP. METHODS: To test this hypothesis a randomized, double-masked, placebo-controlled, three way crossover study was performed in 12 healthy male volunteers. Subjects received on different study days intravenous infusions of the specific ET(A) receptor antagonist BQ-123, the angiotensin converting enzyme inhibitor enalapril or placebo. During these infusion periods subjects were asked to squat for 6 minutes. Choroidal blood flow was measured using a confocal laser Doppler flowmeter and ocular perfusion pressure (OPP) was calculated from mean arterial pressure and intraocular pressure. RESULTS: BQ-123 and enalapril had no effect on basal blood pressure, pulse rate, intraocular pressure, or choroidal blood flow. During isometric exercise, a pronounced increase in mean arterial pressure paralleled by an increase in OPP was observed. Although choroidal blood flow slightly increased during squatting, the increase was much less pronounced than the increase in OPP, indicating some regulatory potential of the choroid. Enalapril did not alter the choroidal pressure-flow relationship during isometric exercise, but BQ-123 induced a significant leftward shift of the pressure-flow curve (P < 0.001). CONCLUSIONS: The present data indicate that ET-1, but not ANG II, plays a role in choroidal blood flow regulation during isometric exercise in healthy humans. Hence, impaired choroidal autoregulation in patients with ocular vascular diseases may arise from an altered endothelin system. Further studies in such patients are warranted to verify this hypothesis.

Adult↗
PubMed2003

Effects of adenosine on intraocular pressure, optic nerve head blood flow, and choroidal blood flow in healthy humans.

PURPOSE: There is evidence from a variety of animal studies that the adenosine system plays a role in the control of intraocular pressure (IOP) and ocular blood flow. However, human data on the effect of adenosine on IOP and choroidal and optic nerve blood flow are not available. METHODS: The effect of stepwise increases in doses of adenosine (10, 20, and 40 micro g/kg per minute, 30 minutes per infusion step) on optic nerve head blood flow, choroidal blood flow, and IOP was determined in a placebo-controlled double-masked clinical trial in 12 healthy male volunteers. Blood flow in the optic nerve head and choroid was measured with laser Doppler flowmetry. In addition, fundus pulsation amplitude in the macula (FPAM) and the optic nerve head (FPAO) were assessed with laser interferometry. RESULTS: Adenosine induced a small but significant decrease in IOP (at 40 microg/kg per minute: 12% +/- 13%), which was significant versus placebo (P = 0.046). In addition, adenosine induced a significant increase in choroidal blood flow (P < 0.001) and optic nerve head blood flow (P = 0.037), and FPAM (P = 0.0014) and tended to increase FPAO (P = 0.057). At the highest administered dose, the effect on choroidal hemodynamic parameters between 14% and 17%, whereas the effect on optic nerve hemodynamic parameters was between 3% and 11%. CONCLUSIONS: These data are consistent with adenosine inducing choroidal and optic nerve head vasodilatation and reducing IOP in healthy humans. Considering the neuroprotective properties of adenosine described in previous animal experiments the adenosine system is an attractive target system for therapeutic approaches in glaucoma.

Adenosine↗
PubMed2002

Effect of pravastatin on responsiveness to N-monomethyl-L-arginine in patients with hypercholesterolaemia.

Improvement of endothelial function in hypercholesterolaemia is attributed to lipid lowering and to pleiotropic effects of statin therapy. We investigated whether responsiveness to inhibition of constitutive NO formation with N-monomethyl-L-arginine (L-NMMA) is improved after 7 and 28 days of pravastatin. Twelve female and four male subjects with mild or moderate primary hypercholesterolaemia were randomized to pravastatin (20 mg per oral (p.o.) n=8) or placebo (n=8) in a double blind parallel group design. Vascular responsiveness was studied by intravenous bolus infusions of L-NMMA (cumulative doses of 3 and 6 mg/kg). Mean arterial blood pressure (MAP) and pulse rate (PR) were measured noninvasively, pulsatile choroidal blood flow was assessed with laser interferometric measurement of fundus pulsation amplitudes (FPA) and renal plasma flow (RPF) was measured by the PAH clearance method. Pravastatin lowered plasma cholesterol levels by 16 and 24% after 7 and 28 days of treatment, respectively (P<0.01). L-NMMA caused comparable changes in MAP, PR and RPF between groups. L-NMMA reduced FPA to a similar extent in both groups before and after 7 days of treatment, but the response to L-NMMA was significantly enhanced after 28 days of pravastatin (21%; P<0.001 vs baseline) and greater than after placebo (15%; P<0.01 vs pravastatin). Pravastatin enhances responsiveness to L-NMMA in the ocular microvasculature. Improved responsiveness is associated with changes in total cholesterol levels.

Australia↗
PubMed2002

Alkalinization increases penetration of lidocaine across the human cornea.

PURPOSE: To test the hypothesis that corneal permeability of lidocaine complies with the principle of nonionic diffusion. SETTING: Department of Ophthalmology and Institute of Pharmacology, Vienna, Austria. METHODS: Human corneas, mounted in an in vitro perfusion system under short-circuit conditions, were exposed on the epithelial (tear) side to lidocaine 4% in a buffered solution of pH 5 or pH 7. The endothelial bathing solutions had a constant pH of 7.4. Both solutions were adjusted to an osmolarity of 290 mOsm/L. The lidocaine permeability of the isolated corneas was assessed from the fluxes of 14C-labeled lidocaine across the tissue, measured at 15-minute intervals for 180 minutes, and corrected for the unidirectional fluxes of 3H-polyethylene glycol, a marker for the extracellular pathway. The corneal tissue content of lidocaine was estimated from the time span until the unidirectional lidocaine fluxes across the cornea reached a steady state. RESULTS: The mean transcorneal fluxes of lidocaine in the steady state (90 to 180 minutes) were 72% higher at pH 7 than at pH 5 (101 mmol/min +/- 37 (SD) versus 59 +/- 34 nmol/min.cornea; P <.002). The corneal content of lidocaine in the steady state was 65% higher at pH 7 than at pH 5 (2.8 +/- 0.9 micromol/cornea versus 1.7 +/- 1.2 micromol/cornea; not significant). CONCLUSIONS: A shift in solution pH from 5 to 7 significantly increased the corneal permeability of topically applied lidocaine. Alkaline pH-adjustment of topical lidocaine solutions is easy to perform by adding sodium bicarbonate. The main clinical advantages of anesthetic solutions buffered at pH 7 are increased penetration rates, effectiveness, prolonged action time, and a reduction in local irritation and lacrimation.

Anesthetics, Local↗
PubMed2002

Adrenoceptor hyporeactivity is responsible for Escherichia coli endotoxin-induced acute vascular dysfunction in humans.

Impaired response to catecholamines contributes to the altered hemodynamics in sepsis, which has been attributed to excessive NO formation. We have studied the systemic hemodynamic and local forearm responses and inducible NO synthase (iNOS) expression during experimental endotoxemia in humans. Escherichia coli endotoxin (lipopolysaccharide [LPS]) was administered at doses of 1 or 2 ng/kg to healthy volunteers. In 10 subjects, the systemic pressor effect of phenylephrine was assessed before and after the administration of LPS. In 9 further subjects, forearm blood flow responses to intra-arterial noradrenaline, acetylcholine, glyceryl trinitrate, and N(G)-monomethyl-L-arginine (L-NMMA) were studied at baseline and after LPS administration. Peripheral blood was collected and analyzed for iNOS mRNA and protein. Four hours after LPS, the response of systolic blood pressure (P<0.0005) and heart rate (P<0.05) to phenylephrine was significantly reduced. In the forearm, noradrenaline-induced vasoconstriction was also reduced by approximately 50% (P<0.01), but L-NMMA responsiveness was unchanged. iNOS mRNA or protein was not increased. Marked vascular adrenoceptor hyporeactivity is detectable in the absence of increased NO activity or iNOS expression in endotoxemia, arguing against major involvement of vascular iNOS activity in the acute systemic vasodilation to LPS.

Adrenergic alpha-Agonists↗
PubMed2002

Exercise training improves vascular endothelial function in patients with type 1 diabetes.

OBJECTIVE-Impaired endothelial function of resistance and conduit arteries can be detected in patients with type 1 diabetes. We studied whether a persistent improvement of endothelial function can be achieved by regular physical training. RESEARCH DESIGN AND METHODS-The study included 26 patients with type 1 diabetes of 20 +/- 10 years' duration and no overt angiopathy; 18 patients (42 +/- 10 years old) participated in a bicycle exercise training program, and 8 patients with type 1 diabetes (33 +/- 11 years old) served as control subjects. Vascular function of conduit arteries was assessed by flow-mediated and endothelium-independent dilation of the brachial artery and of resistance vessels by the response of ocular fundus pulsation amplitudes to intravenous N(G)-monomethyl-L-arginine (L-NMMA) at baseline, after 2 and 4 months of training, and 8 months after cessation of regular exercise. RESULTS-Training increased peak oxygen uptake (VO(2max)) by 13% after 2 months and by 27% after 4 months (P = 0.04). Flow-mediated dilation (FMD) of the brachial artery increased from 6.5 +/- 1.1 to 9.8 +/- 1.1% (P = 0.04) by training. L-NMMA administration decreased fundus pulsation amplitude (FPA) by 9.1 +/- 0.9% before training and by 13.4 +/- 1.5% after 4 months of training (P = 0.02). VO(2max), FMD, and FPA were unchanged in the control group. Vascular effects from training were abrogated 8 months after cessation of exercise. CONCLUSIONS-Our study demonstrates that aerobic exercise training can improve endothelial function in different vascular beds in patients with long-standing type 1 diabetes, who are at considerable risk for diabetic angiopathy. However, the beneficial effect on vascular function is not maintained in the absence of exercise.

Adult↗
PubMed2002

Effects of granulocyte colony stimulating factor on retinal leukocyte and erythrocyte flux in the human retina.

PURPOSE: The blue-field entoptic technique was introduced more than 20 years ago to quantify perimacular white blood cell flux. However, a final confirmation that the perceived corpuscles represent leukocytes is still unavailable. METHODS: The study design was randomized, placebo-controlled, and double masked with two parallel groups. Fifteen healthy male subjects received a single dose of granulocyte colony stimulating factor (G-CSF, 300 microg) and 15 other subjects received placebo. The following parameters were assessed at baseline and at 12 minutes and 8 hours after administration: retinal white blood cell flux, with the blue-field entoptic technique; retinal blood velocities, with bidirectional laser Doppler velocimetry; retinal venous diameter determined with a retinal vessel analyzer; and blood pressure and pulse rate determined by automated oscillometry and pulse oxymetry, respectively. RESULTS: After 12 minutes, G-CSF reduced total leukocyte count from 5.5 +/- 1.4 10(9)/L at baseline to 1.9 +/- 0.4 10(9)/L. This was paralleled by a 35% +/- 11% decrease in retinal white blood cell density. After 8 hours G-CSF increased total leukocyte counts to 20.0 +/- 4.4 10(9)/L. Again, this increase in circulating leukocytes was reflected by an increase in retinal white blood cell density (110% +/- 48%). All effects were significant at P < 0.001. By contrast, none of the other hemodynamic parameters was changed by administration of G-CSF. CONCLUSIONS: The results clearly indicate that the blue-field entoptic technique assesses leukocyte movement in the perimacular capillaries of the retina. Moreover, white blood cell density appears to adequately reflect the number of circulating leukocytes within the retinal microvasculature. Hence, an increase in retinal white blood cell density does not necessarily reflect retinal vasodilatation.

Adult↗
PubMed2002

Identification of estrogen and progesterone receptor mRNA expression in the conjunctiva of premenopausal women.

PURPOSE: The purpose of the present study was to identify the expression of estrogen and progesterone receptor mRNA and of estrogen and progesterone receptor protein in the conjunctiva of healthy women. METHODS: Specimens of conjunctival tissue of 10 premenopausal women (age range, 13-38 years) were obtained during ophthalmic surgery in patients under general anesthesia. Specimens of approximately 4 mm(2) were taken from superior, nasal, or temporal bulbar conjunctiva adjacent to the bulbus and were immediately deep frozen with liquid nitrogen. Four women underwent strabismus surgery, two had phacoemulsification, and four had vitrectomy. Only three women were taking oral contraceptives. The expression of estrogen receptor (ER)-alpha, ERbeta, and progesterone receptor (PR) mRNA was analyzed by RT-PCR. Western blot analysis on nuclear extracts was performed with the anti-ERalpha mouse monoclonal antibody AB-15, the anti-ERbeta mouse monoclonal antibody 6B12, and the anti-PR mouse monoclonal antibody PgR 636. RESULTS: In two samples, ERalpha, ERbeta, and PR mRNAs were not accessible because of highly degraded RNA. In the remaining eight samples, an appearance rate of 100% was obtained for all three mRNAs. Similarly, an appearance rate of 100% was obtained for ERalpha, ERbeta, and PR protein in nine tissue samples accessible for analysis; one sample could not be analyzed due to a low amount of tissue. CONCLUSIONS: This study confirms the existence of estrogen and progesterone receptors in the human conjunctiva of premenopausal females. Because the proteins of estrogen and progesterone were also found in this study's specimens, the data indicate that the conjunctiva is a target site for sex steroids. Future studies are needed to elucidate the role of these receptors in ocular diseases involving the conjunctiva.

Adolescent↗