Biomedical subjects

L Schmetterer

Publications and source records attributed to L Schmetterer.

At least 73 records · Page 4Linked to original sources

PubMed1998

Effects of histamine and nitric oxide synthase inhibition on plasma levels of von Willebrand factor antigen.

Endothelial cells release von Willebrand factor (vWf) either constitutively or by a regulated pathway. Based on various studies in vitro, we hypothesized that the stimulatory action of histamine on vWf release could also be induced in vivo and that it may be inhibited by endogenous production of nitric oxide (NO). Nine healthy subjects received placebo or one of two dosages of a primed constant infusion of the NO-synthase inhibitor N-monomethyl-L-arginine (L-NMMA) in a randomized, double-blind, three-way crossover trial. Histamine was coinfused for 15 minutes at 0.16 microg/kg/min after 30 minutes of pretreatment with either placebo or L-NMMA. Thirty minutes after either the low or the high L-NMMA dose was started, which caused, respectively, a 40% decrease and a 60% decrease in exhaled end expiratory NO level (p = 0.008), there was no increase in von Willebrand factor antigen (vWf-Ag) level (p > 0.05). Histamine caused an 11% (95% confidence interval (CI): 0.4% to 22%; p = 0.011) increase in vWf-Ag level at 125 minutes. After pretreatment with the low and the high L-NMMA doses, vWf-Ag level increased by 18% (Cl: 5% to 31%; p = 0.011) and by 29% (CI: 15% to 42%; p = 0.008), respectively. At 125 minutes, vWf-Ag level was significantly higher after either L-NMMA pretreatment when compared with the results after histamine alone (p < 0.05). In conclusion, the infusion of histamine increased vWf-Ag level, and the inhibition of NO-synthase enhanced this effect, whereas it did not by itself elevate vWf-Ag level. Thus endogenously produced NO may dampen the regulated pathway of vWf secretion; it will be interesting to investigate whether endogenous NO production also inhibits vWf release caused by other stimulators.

Antigens↗

PubMed1998

Role of nitric oxide in exercise-induced vasodilation in man.

Nitric oxide (NO) is a potent endothelium-derived vasodilator, which is known to play an important role in the regulation of resting vascular tone in animals and humans. However, the degree to which NO is involved in exercise-induced vasodilation in the skeletal muscle remains unclear. We studied the effect of N-monomethyl-L-arginine (L-NMMA) in a randomized, double-blind, placebo controlled cross over study in 16 young, healthy volunteers ( 8 male, 8 female) at rest and during bicycle exercise stress test. L-NMMA was given as a bolus of 3 mg/kg over 5 minutes followed by a continuous i.v. infusion of 50 microg/kg/min over 75 minutes. Subjects underwent a symptom-limited graded bicycle stress test with a 25 Watt increase in workload every 5 minutes. Skin and muscle blood flow were measured by laser Doppler flowmetry. L-NMMA slightly increased mean arterial blood pressure and decreased NO exhalation, but had no effect on pulse rate, oxygen consumption (VO2), skin or muscle blood flow at rest. Moreover, L-NMMA exerted no effect on exercise-induced changes in hemodynamics. Our results suggest that submaximal inhibition of NO-synthase with L-NMMA at doses that induce moderate hemodynamic changes does not affect exercise induced vasodilation.

Adult↗

PubMed1998

Systemic and renal effects of an ET(A) receptor subtype-specific antagonist in healthy subjects.

1. Endothelins (ETs) might play a pathophysiological role in a variety of vascular diseases. The aim of the present study was to characterize the effects of BQ-123, a specific ET(A) receptor antagonist on systemic and renal haemodynamics in healthy subjects. This was done at baseline and during infusion of exogenous ET-1. 2. The study was performed in a balanced, randomized, placebo-controlled, double blind 4 way cross-over design in 10 healthy male subjects. Subjects received co-infusions of ET-1 (2.5 ng kg(-1) min(-1) for 120 min) or placebo and BQ-123 (15 microg min(-1) for 60 min and subsequently 60 microg min(-1) for 60 min) or placebo. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were assessed by the para-aminohippurate (PAH) and the inulin plasma clearance method, respectively. 3. BQ-123 alone had no renal or systemic haemodynamic effect. ET-1 significantly reduced RPF (-24%, P<0.001) and GFR (-12%, P=0.034). These effects were abolished by co-infusion of either dose of BQ-123 (RPF: P=0.0012; GFR: P=0.020). 4. BQ-123 reversed the renal haemodynamic effects induced by exogenous ET-1 in vivo. This indicates that vasoconstriction in the kidney provoked by ET-1 is predominantly mediated by the ET(A) receptor subtype.

Adult↗

PubMed1998

Exogenous L-arginine does not affect angiotensin II-induced renal vasoconstriction in man.

AIMS: It has been suggested that provision of the substrate of nitric oxide (NO) synthesis, L-arginine, might influence the effects of renal vasoconstrictors. We have therefore studied the effects of pretreatment or concomitant administration of L-arginine on angiotensin II (ANG II)-increased renovascular resistance. METHODS: The study was conducted in a double-blind, randomized, cross-over design. Eight healthy subjects were assigned to placebo or a continuous intravenous coinfusion of ANG II (5.0 ng kg[-1] min[-1], infusion period 75 min) with L-arginine (17 mg kg[-1] min[-1], infusion period 30 min). Nine further subjects received a continuous infusion of ANG II with or without pretreatment of L-arginine. Changes in renal plasma flow (RPF) were estimated by the steady state clearance of PAH. RESULTS: L-arginine alone increased RPF to 110 +/- 10% over baseline (P < 0.003). The ANG II-induced decrease in RPF was not affected by pretreatment or coinfusion of L-arginine. CONCLUSIONS: Our results demonstrate that a counterregulatory response of the renal vasculature to high levels of ANG II does not depend on exogenous L-arginine. In healthy subjects, this lack of functional antagonism at the renal vasculature is therefore not a result of NO substrate availability.

Adult↗

PubMed1998

Age dependence of choroidal blood flow.

OBJECTIVE: To investigate the age dependence of choroidal blood flow. DESIGN: A cross-sectional study. SETTING: Department of Clinical Pharmacology, Vienna University. PARTICIPANTS: A total of 130 healthy volunteers between the ages of 19 and 83 years. MEASUREMENTS: Fundus pulsation amplitude (FPA) with a recently developed laser interferometric method, mean arterial pressure (MAP) with an automated oscillometric device, intraocular pressure (IOP) with an applanation tonometer, and ocular perfusion pressure (OPP) as calculated from MAP and IOP. RESULTS: There was a significant correlation of FPA with age r = -0.242 (P = .005). MAP, IOP, and OPP showed a significant positive correlation with age. Multiple regression analysis showed that FPA is associated with age but not with MAP, IOP, or OPP. CONCLUSION: Choroidal blood flow is reduced in older subjects, which argues in favor of an increase in ocular vascular resistance with age. This may be a risk factor in the development of common ocular diseases such as age-related macular degeneration or glaucoma.

Adult↗

PubMed1998

Effects of acetazolamide on choroidal blood flow.

BACKGROUND AND PURPOSE: The acetazolamide provocation test is commonly used to study cerebrovascular vasomotor reactivity. On the basis of the effect of a carbonic anhydrase inhibitor in the central nervous system, we hypothesized that acetazolamide may also increase blood flow in the human choroid. METHODS: In a placebo-controlled, randomized, double-blind, three-way crossover design, acetazolamide (500 mg or 1000 mg i.v.) or placebo was administered to nine healthy subjects. The effect of acetazolamide was studied at 15-minute intervals for 90 minutes. Pulsatile choroidal blood flow was assessed with laser interferometric measurement of fundus pulsation. In addition, mean blood flow velocity and resistive index in the ophthalmic artery were measured with Doppler sonography. In a second study in six healthy subjects, we assessed the effect of acetazolamide (1000 mg i.v.) on intraocular pressure. RESULTS: Acetazolamide increased fundus pulsation amplitude in a dose-dependent manner (1000 mg: +33%; 500 mg: +20%; P<0.001, ANOVA). The effect of acetazolamide on MFV (1000 mg: +18%; 500 mg: +8%; P=0.003, ANOVA) and RI (1000 mg: -4%; 500 mg: -2%; P=0.006, ANOVA) was less pronounced but also significant. Acetazolamide did not induce any changes in systemic hemodynamic parameters but significantly decreased intraocular pressure (1000 mg: -37%; P<0.0001). CONCLUSIONS: The present data show for the first time that intravenously administered acetazolamide increases choroidal blood flow in humans. This phenomenon therefore indicates that the acetazolamide provocation test may qualify as a tool to investigate ocular vasomotor reactivity in a variety of ocular diseases. Moreover, the increase in choroidal blood flow after carbonic anhydrase inhibition can be expected to contribute to the therapeutic efficacy of carbonic anhydrase inhibitors in glaucoma.

Acetazolamide↗

PubMed1998

Short-term oral pentoxifylline use increases choroidal blood flow in patients with age-related macular degeneration.

OBJECTIVE: To study the ocular hemodynamic effects of a 3-month oral treatment with pentoxifylline in patients with nonexudative age-related macular degeneration. DESIGN: Double-blind, placebo-controlled, randomized, parallel group study. SETTING: Outpatient clinic of the Department of Ophthalmology, Vienna University, Vienna, Austria, that specializes in age-related macular degeneration. METHODS: Forty patients with age-related macular degeneration received pentoxifylline (400 mg 3 times a day orally, n=20) or placebo (n=20) for 3 months. Retinal blood flow was assessed by scanning laser Doppler flowmetry and pulsatile choroidal blood flow was assessed by laser interferometric measurement of fundus pulsation amplitude. MAIN OUTCOME MEASURES: Changes in retinal blood flow and fundus pulsation amplitude. RESULTS: Four patients receiving pentoxifylline and 3 patients receiving placebo discontinued medication because of nausea. In the remaining subjects, the use of pentoxifylline increased ocular fundus pulsation amplitude (P<.001 vs placebo and baseline). The maximum increase was 28% after 3 months. In contrast, retinal blood flow was not changed by the use of pentoxifylline. CONCLUSIONS: A 3-month course of oral pentoxifylline treatment increases choroidal but not retinal blood flow in patients with age-related macular degeneration. These data strongly support the concept that pentoxifylline might be useful in the treatment of age-related macular degeneration. Long-term clinical outcome trials are now warranted to test this hypothesis.

Administration, Oral↗

PubMed1998

Noninvasive investigations of the normal ocular circulation in humans.

PURPOSE: To compare the reproducibility of laser interferometric measurements of fundus pulsation, pneumatonometric measurement of pulse amplitude (PA) and pulsatile ocular blood flow (POBF), and Doppler ultrasonic measurements of blood flow velocity in the ophthalmic artery (OA) and the posterior ciliary arteries (PCAs) and to investigate the association of the results obtained with these methods and to characterize ocular hemodynamics during Valsalva maneuver and isometric handgrip. METHODS: All studies were performed in healthy subjects. Fundus pulsation (n = 48), POBF (n = 24), and blood flow velocities (n = 24) were measured at baseline and during the Valsalva maneuver and isometric handgrip. Intraclass correlation coefficients were calculated for test/retest variability, for short-term variability, and for interobserver variability. RESULTS: Intraclass correlation coefficients were between 0.95 and 0.98 for fundus pulsation measurements, between 0.54 and 0.76 for pneumatonometric measurements, between 0.44 and 0.88 for Doppler sonographic measurements in the OA and between 0.32 and 0.60 in the PCAs. There was a high degree of association between pneumatonometric parameters and fundus pulsation amplitude. Valsalva maneuver significantly reduced fundus pulsations, PA, and POBF, whereas isometric handgripping did not change these parameters. CONCLUSIONS: The reproducibility of fundus pulsation measurements was excellent. Reproducibility of pneumatonometric parameters and ultrasonographic measurements in the OA was satisfactory. Reproducibility of ultrasonographic measurements in the PCAs was low. Data obtained during the autonomic stimuli experiments argue against the sole use of systems to measure pulsatile blood flow, if no additional data on flow pulsatility are available. At least in cases when changes in blood pressure are likely to occur the ratio of pulsatile to nonpulsatile blood flow might not be constant and POBF might not be an adequate measure of total ocular blood flow.

Adult↗

PubMed1998

Eye elongation during accommodation in humans: differences between emmetropes and myopes.

PURPOSE: The pathophysiology and pathogenesis of myopia are still a matter of controversy. Exaggerated longitudinal eye growth is assumed to play an important role in the development of myopia. A significant correlation between refraction and amount of near-work has been reported. However, current knowledge of changes of axial eye length with accommodation is limited because clinical ultrasound biometry does not provide the precision and resolution required to thoroughly investigate these phenomena. METHODS: Partial coherence interferometry (PCI), a noninvasive biometric technique, uses laser light with short coherence length in combination with interferometry to achieve precision in the micrometer to submicrometer range and resolution of 10 microm. In the present study this technique was used to investigate axial eye length changes in 11 emmetropic and 12 myopic eyes during monocular fixation at the far and near point. In 7 subjects, the contralateral eye has also been measured to investigate interocular differences in eye elongation. RESULTS: All investigated eyes elongated during accommodation. This elongation was more pronounced in emmetropes than in myopes (P < 0.001). Mean accommodation-induced eye elongations of 12.7 microm (range, 8.6-19.2 microm) and 5.2 microm (range, 2.1-9.5 microm), corresponding to a dioptric change of approximately -0.036 D and -0.015 D, were obtained for emmetropes and myopes. No significant difference in accommodative amplitudes between groups (5.1 +/- 1.2 D [range, 3.8-7.1 D] versus 4.1 +/- 2.0 D [range, 1.0-7.1 D]; P = 0.14) was detected. No significant interocular difference in accommodation-induced eye elongation was revealed (P = 0.86). Also, a mean backward movement of the posterior lens pole of 38 microm (range, 9-107 microm) was observed in both study groups. CONCLUSIONS: The detected eye elongation can be explained by the accommodation-induced contraction of the ciliary muscle, which results in forward and inward pulling of the choroid, thus decreasing the circumference of the sclera, and leads to an elongation of the axial eye length. Finally, it was demonstrated that PCI, in contrast to clinical ultrasound, is capable of characterizing eye length changes during accommodation in humans.

Accommodation, Ocular↗

PubMed1997

The effect of systemic nitric oxide-synthase inhibition on ocular fundus pulsations in man.

There is experimental evidence that endothelium derived nitric oxide is involved in the regulation of ocular vascular tone. The purpose of this study was to investigate the effects of NO-synthase inhibition by N-monomethyl-L-arginine (L-NMMA) on ocular fundus pulsations in young healthy volunteers. Three milligrams per kilograms L-NMMA were administered i.v. over 5 minutes. Protocol 1: Measurements of blood pressure, pulse rate, fundus pulsation amplitude, NO-exhalation, and cardiac output were performed at baseline and 10, 30, 60, 90, 150, and 300 minutes after L-NMMA infusion (n = 8). Fundus pulsation amplitude, which has been shown to estimate the pulsatile component of the choroidal blood flow, was recorded with a recently developed laser interferometer. Protocol 2: Measurements of blood pressure, pulse rate, fundus pulsation amplitude, NO-exhalation, and blood flow velocity in the ophthalmic artery were performed in a randomized, placebo controlled cross over study (n = 10). Ten minutes after L-NMMA administration fundus pulsation amplitude decreased by 23 +/- 2% (protocol 1) and 19 +/- 1% (protocol 2, P < 0.01 each), cardiac output by 12 +/- 2% (P < 0.01), and exhaled NO by 55 +/- 6% (protocol 1) and 41 +/- 6% (protocol 2, P < 0.01 each). All parameters returned to baseline values within the 300 minutes observation period, with a faster recovery of fundus pulsation amplitude than of cardiac output and exhaled NO. Blood pressure, pulse rate, and ophthalmic artery blood flow velocity showed only minor changes during and after administration of L-NMMA. Our results suggest that systemic NO-synthase inhibition reduces pulsatile choroidal and most likely total choroidal blood flow in humans. The recovery of vascular tone in choroidal vessels seems to be different from the cardiovascular response. Our findings indicate that reduced fundus pulsations after L-NMMA are caused by systemic factors as well as by local reactions of the choroidal vasculature.

Adult↗

PubMed1997

Fundus pulsation measurements in diabetic retinopathy.

BACKGROUND: There is experimental evidence that retinal blood flow is impaired in patients with diabetes mellitus. Much less attention has been paid to choroidal blood flow. Hence it was the aim of the present study to investigate choroidal blood flow in diabetic retinopathy. METHODS: A new non-invasive laser interferometric technique was used to measure fundus pulsations in the macula. The fundus pulsation amplitude, which is the maximum distance change between cornea and retina during the cardiac cycle, is a measure of local pulsatile blood flow. The eyes (n = 214) were divided into four groups according to the modified Airlie House classification: (1) no retinopathy (control group), (2) background retinopathy, (3) moderate to severe preproliferative retinopathy, (4) proliferative retinopathy. In 83 eyes of different group fundus pulsation measurements were repeated after 1-6 weeks. RESULTS: Fundus pulsation amplitudes were significantly smaller in group 4 than in the control group (P < 0.027). The reproducibility of the measurements was high and did not differ among the study groups. CONCLUSIONS: Local fundus pulsations in the macula are reduced in proliferative diabetic retinopathy, which is compatible with previous findings of reduced choroidal blood flow in late stages of the disease. Laser interferometric measurement of fundus pulsations is non-contactile, assures optimal comfort for the patient and could be used for the long-term observation of patients with diabetes mellitus.

Adult↗

PubMed1997

Effects of antiglaucoma drugs on ocular hemodynamics in healthy volunteers.

BACKGROUND AND PURPOSE: There is evidence that ocular blood flow plays a critical role in the clinical course of glaucoma. Hence a reduction in ocular blood flow due to topical antiglaucoma treatment should be avoided. The purpose of this study was to characterize the effect of antiglaucoma drugs on ocular hemodynamics. METHODS: In a double-blind, placebo-controlled, randomized crossover study, we investigated the effects of single topical doses of five beta-blocking agents (befunolol, betaxolol, levobunolol, metipranolol, and timolol), two adrenergic agents (clonidine and dipivefrin [INN, dipivefrine]), and a parasympathomimetic agent (pilocarpine) on ocular and systemic hemodynamics in healthy subjects (n = 10). Fundus pulsation amplitudes in the macula and the optic disc were measured to characterize pulsatile choroidal and optic disc blood flow, respectively. Moreover, central retinal and ophthalmic artery blood flow velocities were measured by Doppler ultrasound. RESULTS: Befunolol, metipranolol, timolol, clonidine, and dipivefrin reduced fundus pulsations in the macula and the optic disc (-9% to -14% versus baseline). In contrast, betaxolol, levobunolol, and pilocarpine had no effect on fundus pulsations. Antiglaucoma drugs had no effect on either blood flow velocities in the central retinal or the ophthalmic artery or systemic hemodynamics. CONCLUSIONS: Our results indicate that befunolol, metipranolol, timolol, clonidine, and dipivefrin reduce choroidal and optic disc blood flow. This could be caused by drug diffusion to the choroid, which may cause vasoconstriction. Ocular blood flow reduction was not observed with betaxolol, levobunolol, or pilocarpine. The lack of effect of all drugs under study on central retinal blood flow velocity might partially be the result of autoregulative mechanisms. Because optic nerve head blood flow likely plays a critical role in the clinical course of glaucoma, the use of antiglaucoma drugs, which reduce blood flow, should be reconsidered.

Adrenergic Agents↗

PubMed1997

Characterization of angiotensin-II effects on cerebral and ocular circulation by noninvasive methods.

AIMS: The role of the renin-angiotensin-system (RAS) in the cerebral and ocular circulation is still a matter of controversy. In vitro and animal data lead to partially contradicting results. However, direct investigation of locally generated angiotensin II (Ang II) in humans is not possible in vivo. Hence, we hypothesised that it might be possible to characterize local effects of Ang II by comparing systemic and local haemodynamic parameters during exogenous Ang II infusion. METHODS: In a placebo-controlled, double-blind, two-way cross over study blood flow velocities in the middle cerebral and the ophthalmic artery and ocular fundus pulsations were measured during stepwise increasing doses of Ang II in 10 healthy subjects. Blood flow velocities were assessed by Doppler sonography, fundus pulsation amplitudes (FPA), which estimate local pulsatile ocular blood flow were measured by laser interferometry. Additionally, systemic blood pressure and pulse rate were measured. RESULTS: Ang II dose-dependently decreased resistive index (RI) and increased mean flow velocities (MFV) in both arteries. Fundus pulsation amplitude was dose-dependently decreased by Ang II, whereas mean arterial pressure (MAP) was significantly increased. Pulse pressure amplitude (PPA) was not affected by Ang II administration. There was a high degree of correlation between changes in RIs and the analogously calculated PPA/systolic blood pressure during Ang II infusion, which indicates that the changes in RI after Ang II administration can be attributed to changes in systemic haemodynamics. Calculation of total local ocular blood flow from fundus pulsation amplitudes and changes in flow pulsatility in the ophthalmic artery further argue against significant blood flow changes after Ang II administration. CONCLUSIONS: Interpretation of data from Doppler sonography and laser interferometry must be done very carefully when concomitant changes in systemic haemodynamics occur. RI cannot necessarily be taken as an index of distal vascular resistance in these cases and changes in MFV can be caused by changes in vessel diameter or in blood flow. Moreover, FPA cannot be taken as a measure of ocular blood flow if no additional data on flow pulsatility are available. The combination of our systemic and local haemodynamic data indicates that cerebral and ocular circulation are comparably insensitive to changes in local Ang II concentrations. Fundus pulsation and blood flow velocity measurements indicate that neither choroidal nor optic nerve head blood flow are significantly affected by administration of Ang II.

Adult↗

PubMed1997

Effects of losartan on cerebral and ocular circulation in healthy subjects.

AIMS: The introduction of specific inhibitors of AT1 receptors, such as losartan, has enabled the investigation of the renin-angiotensin-system (RAS) in humans in vivo. We studied the role of the RAS in the cerebral and ocular circulation in healthy subjects. Haemodynamic effects of orally administered losartan were investigated with non-invasive methods. METHODS: In a placebo-controlled randomized, double-blind two way crossover design losartan (100 mg orally) or placebo was administered in 10 healthy subjects. The effect of losartan was studied at hourly intervals for 8 h. In addition, the effect of losartan on haemodynamic changes induced by exogenous angiotensin II (Ang II) was assessed. Blood flow velocities in the ophthalmic and the middle cerebral artery (OA, MCA) were measured with Doppler sonography. Pulsatile choroidal blood flow was estimated with laser interferometric measurement of fundus pulsation. RESULTS: Losartan significantly increased fundus pulsation amplitude (+11%, 95% CI: 5 to 16% P<0.0001), tended to increase resistive index in the ophthalmic artery (+12%, 95% CI: 0 to 23%) and tended to decrease mean arterial pressure (-15%, 95% CI: -23 to -1%). Ang II induced effects on cerebral, ocular and systemic haemodynamics were prevented by preceding administration of losartan. CONCLUSIONS: The present data suggest that Ang II is not a major determinant of cerebral and ocular blood flow in vivo. The observed changes in cerebral and ocular haemodynamic parameters after losartan administration reflect effects on systemic blood pressure.

Adult↗

PubMed1997

Ocular and systemic reactivity to isoprenaline in patients with insulin-dependent diabetes mellitus.

There is experimental evidence of decreased beta-adrenergic myocardial sensitivity in patients with insulin-dependent diabetes mellitus (IDDM). In the present study we hypothesized that the ocular response to isoprenaline, as a consequence of increased arterial vessel rigidity, might also be blunted in patients with IDDM. We therefore compared the correlation between systemic pulse pressure amplitude (PPA) and fundus pulsation amplitude (FPA) during intravenous isoprenaline administration in 11 otherwise healthy IDDM patients and 11 healthy control subjects. Ocular fundus pulsations were measured by a recently developed laser interferometric method. Isoprenaline increased PPA in both study groups in a dose-dependent way, but the response was significantly less in IDDM patients (at 0.8 microgram min-1: +38% in control subjects, +27% in IDDM patients, P < 0.05 between groups). Moreover, a dose-dependent increase in FPA was observed, which again was more pronounced in healthy subjects (at 0.8 microgram min-1: +45% in controls, +17% in IDDM patients, P < 0.005 between groups). The regression line between PPA and FPA was very close to the 45 degrees line in healthy subjects, whereas it was significantly flattened in IDDM patients. In conclusion, linear regression between PPA and FPA during isoprenaline suggests arterial stiffening in patients with IDDM. Hence, comparison of systemic PPA and FPA during isoprenaline provocation may be a useful method of estimating changes in arterial capacitance in patients with diabetes mellitus.

Adrenergic beta-Agonists↗

PubMed1997

Nitric oxide synthase inhibition in the histamine headache model.

Histamine has been widely used experimentally to induce headache in healthy subjects and migraine in migraineurs. There is evidence that the vascular effects of histamine are at least partially mediated by nitric oxide (NO). Hence we hypothesized that subjective symptoms and hemodynamic effects of histamine could be reduced by systemic NO-synthase inhibition. We therefore studied the effect of pretreatment with N-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of NO-synthase, or placebo on headache, flush and discomfort scores during histamine infusion. Additionally, blood flow velocities in the middle cerebral and the ophthalmic artery and ocular fundus pulsations were measured. Whereas L-NMMA blunted the effect of histamine in the ophthalmic artery and the ocular circulation, NO-synthase inhibition did not mitigate subjective symptoms. Histamine did not affect mean blood flow velocities in the middle cerebral artery. Hence, we conclude that NO-synthase inhibition reduces the histamine-induced vascular effects in the ocular circulation, but is not sufficient to attenuate or abort the subjective symptoms provoked by histamine infusion.

Adult↗

PubMed1997

Effects of changes in intraocular pressure on human ocular haemodynamics.

PURPOSE: Myogenic autoregulation is the ability of a vascular bed to maintain blood flow despite changes in perfusion pressure. Ocular perfusion pressure is defined as the difference between ocular arterial pressure and ocular venous pressure, the latter dependent on intraocular pressure (IOP). The aim of the present study was to investigate the effect of moderate increases in IOP on ocular haemodynamics. METHODS: Changes in IOP (+ 10 mmHg, +20 mmHg) were induced by a suction cup in 10 healthy subjects. Ocular fundus pulsations in the macula and the optic disc were measured by laser interferometry; blood flow velocities in the central retinal artery (CRA) and in the ophthalmic artery (OA) were measured by Doppler sonography. RESULTS: Changes in IOP caused a significant reduction in fundus pulsations, which was more pronounced in the macula (at +10 mmHg: -9 +/- 2%, p < 0.01; at +20 mmHg: -19 +/- 3%, p < 0.001) than in the optic disc (at +10 mmHg: -5 +/- 2% (ns); at +20 mmHg: -9 +/- 3%, p < 0.01). Mean flow velocity in the CRA was reduced by -5 +/- 3% at +10 mmHg (ns) and by -14 +/- 5% at +20 mmHg (p < 0.005), resistive index was increased by +4 +/- 1% at +10 mmHg (p < 0.05) and by +6 +/- 2% at +20 mmHg (p < 0.01). In contrast, a rise in IOP did not affect blood flow parameters in the OA. CONCLUSIONS: Our results from fundus pulsation measurements indicate that choroidal blood flow decreases when IOP is increased. The Doppler sonographic findings in the CRA indicate reduced blood flow velocity in this artery during raised IOP.

Adult↗

PubMed1997

Effects of endothelin-1 (ET-1) on ocular hemodynamics.

PURPOSE: There is evidence from in vitro and animal data that endothelin-1 (ET-1) plays an important role in ocular blood flow. The aim of the present study was to investigate the effect of systemic ET-1 administration on ocular circulation in healthy subjects. METHODS: In a double blind, placebo-controlled, randomized, 2-way cross over study in 10 healthy male subjects, we administered stepwise, increasing doses of ET-1 (0 (saline), 1.25, 2.5 and 5.0 ng/kg/minutes; 20 minutes per dose (level) or placebo. Blood flow velocity in the ophthalmic artery as well as ocular fundus pulsations in the macula and the optic disc, and systemic hemodynamic parameters were measured. RESULTS: ET-1 dose-dependently reduced fundus pulsations in the macula (maximum effect -12 +/- 2% versus baseline; p < 0.001 versus baseline and placebo) and the optic disc (maximum effect: -19 +/- 5% versus baseline; p < 0.001 versus baseline and placebo), but did not affect blood flow velocity in the ophthalmic artery or systemic hemodynamics. CONCLUSIONS: Endothelin-1 reduces pulsatile blood flow in the choroid and the optic disc at doses which do not affect systemic hemodynamics or flow velocity in the ophthalmic artery. These results indicate that ocular circulation is particularly sensitive to changes in local ET-1 concentration and confirms the hypothesis that ET-1 may play a role in ocular vascular diseases.

Adult↗