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Biomedical subjects

J Flammer

Publications and source records attributed to J Flammer.

At least 109 records · Page 6Linked to original sources
PubMed1998

beta-Adrenergic agonist-induced nitrite production in isolated pig ciliary processes.

BACKGROUND: We performed an experiment to assess whether in ciliary processes adrenergic-receptor agents can modulate the production of nitrite, an oxidized metabolite of nitric oxide (NO). METHODS: The porcine ciliary processes and the iris were dissected and stored at -20 degrees C. Later, tissues were thawed, and nitrite measured by Griess reaction, before and 2 h after exposure to various drugs. RESULTS: In the ciliary processes, but not in the iris, the alpha-, beta-adrenergic receptor agonist, norepinephrine (0.01-10 microM), increased nitrite production (95 +/- 12%, P < 0.01). The norepinephrine-induced (0.1 microM) nitrite production was inhibited by the inhibitor of NO synthase, N omega-nitro-L-arginine methyl ester (0.5 mM; P < 0.05) and by the non-selective beta-adrenergic receptor antagonist, propranolol (10 microM; P < 0.01), but not by the non-selective alpha-adrenergic receptor antagonist, phentolamine (10 microM). CONCLUSION: In isolated porcine ciliary processes, beta-adrenergic receptor stimulation increases NO production.

Adrenergic beta-Agonists↗
PubMed1998

Optic nerve blood-flow abnormalities in glaucoma.

Glaucoma can be defined as an optic nerve disease with typical morphological and functional changes. There are many risk factors associated with this neuropathy. The best known factor is an increased intraocular pressure. There are, however, many other risk factors. Among them, vascular factors play a major role. Although such vascular factors have been postulated more than hundred years ago, it is only recently that the physiology and pathophysiology of the optic nerve head circulation is, to some extent, understood. New instruments have been developed to measure ocular blood flow including blood flow in the optic nerve head. Although most of the studies indicate that circulation is changed in glaucoma patients, there is little association between glaucoma and arteriosclerosis. The main cause for the circulation disturbance in glaucoma seems rather to be a vascular dysregulation leading to local vasospasm and to systemic hypotension.

Animals↗
PubMed1998

[Latanoprost--a new prostaglandin F2 alpha analog in therapy of glaucoma--an overview].

An ideal glaucoma drug reduces intraocular pressure profoundly and long-lastingly without known major side effects. Latanoprost, a new prostaglandin F2 alpha-analogue, indeed has these properties. However, we need long-term experience to exclude major, clinically relevant side effects. The influence of latanoprost on ocular circulation also needs further evaluation. Nevertheless, the clinician does have a new and very potent drug to reduce intraocular pressure. Literature search by Medline.

Animals↗
PubMed1998

Abnormalities of microcirculation in glaucoma: facts and hints.

Many risk factors associated with glaucoma have been identified recently. The best known of these is increased intraocular pressure (IOP). Among the others, however, vascular risk factors play a major role. Although such vascular factors were already postulated more than 100 years ago, only recent technical developments have afforded systematic investigations of associated microcirculatory disturbances and basic principles of blood flow regulation. In glaucoma, besides IOP, vascular dysregulation (such as local vasospasm and systemic hypotension, resulting in impaired autoregulation of blood flow in the optic nerve head, the choroid, and other ocular tissues) seems to be a major risk factor. However, multiple coacting factors, which are not limited to the eye but are, rather, symptoms of a systemic disease, seem to be involved in the damaging process.

Choroid↗
PubMed1998

The psychology of the glaucoma patient.

Under physiological conditions, intraocular pressure (IOP) is controlled by the autonomic and central nervous systems. Correspondingly, nerve fibers and neurotransmitters are present in ciliary body and trabecular meshwork. IOP responds to physical as well as psychological stimuli in healthy individuals. In patients with dysregulated IOP, e.g., in those with primary open-angle glaucoma, emotional instability without a specific personality pattern could be found. Whereas the statistical association between emotional changes and glaucoma is obvious, the causal relationship remains to be clarified. It is at least plausible that psychic stress may have an influence on IOP. However, the sequence of the events is unknown (emotional disturbance can be the result of the disease or it can be a primary sign of a nervous dysfunction). Therefore, it seems meaningful--in addition to standard glaucoma therapy--to try to improve the patient's emotional condition, both for treatment of the glaucoma and for the patient's general quality of life.

Exercise↗
PubMed1998

Endothelium-derived vasoactive substances relevant to normal-tension glaucoma.

Glaucoma is a progressive optic neuropathy that has a multi-factorial etiology. The most important risk factor is certainly an increased intraocular pressure. However, clinical observations have indicated that factors other than increased intraocular pressure also damage the neural tissue in glaucomatous optic neuropathy. The most prominent of these to be vascular dysregulation. Vascular tone is permanently regulated by a number of regulatory systems and factors, and the endothelial cell layer acts as an important mediator for the response to these factors. According to recent evidence, glaucomatous optic neuropathy may be associated with changes in endothelium-dependent vascular regulation. Consequently, therapeutic approaches based on vasodilator drugs acting via endothelium-derived substances are being developed. Although promising preliminary studies have been performed, the clinical relevance of such treatment remains to be clarified.

Animals↗
PubMed1998

Effect of carbogen, oxygen and intraocular pressure on Heidelberg retina flowmeter parameter 'flow' measured at the papilla.

The aim of the study was to evaluate whether the Heidelberg retina flowmeter (HRF), a new device for retinal and anterior optic nerve blood flow assessment, can gauge, at least semiquantitatively, a known effect such as an increase in optic nerve blood flow by hypercapnia or a decrease in optic nerve blood flow by hyperoxia or high intraocular pressure (IOP). Measurements with the HRF were obtained at the papilla of three groups of 5 young healthy subjects (1) at baseline and after breathing 5% carbogen, (2) at baseline and after breathing 100% oxygen and (3) at baseline and after increasing IOP to 20 and 50 mm Hg. The changes in the value of the HRF parameter 'flow' were analyzed by means of a paired Student's t test. Breathing 100% oxygen for 7 min resulted in a statistically significant decrease of 34.7+/-2.5% (mean+/-SEM) in HR parameter 'flow' (p < 0.01) at the papilla. Breathing 5% carbogen for 7 min resulted in a statistically significant increase of 18.3+/-2.6% in HRF parameter 'flow' (p = 0.024). Increasing IOP to 20 mm Hg did not result in a statistically significant change in HRF parameter 'flow' (-9.6+/-7.4%; p = 0.13). Increasing IOP from 20 to 50 mm Hg, however, resulted in a statistically significant decrease of 40.1+/-6.6% in HRF parameter 'flow' (p = 0.003). With the applied stimuli, the HRF parameter 'flow' changed in the expected direction, i.e. an increase with hypercapnia and a decrease with hyperoxia or high IOP. The simplicity of use of the HRF instrument suggests that it might be well suited for a non-invasive, at least semiquantitative, assessment of changes in blood flow at the papilla.

Adult↗
PubMed1998

Measurement of intraocular pressure with a modern noncontact tonometer.

PURPOSE: To evaluate the intraocular pressure (IOP) in a population without known glaucoma as measured by means of a noncontact tonometer (NCT). METHODS: IOP values of 842 persons, measured by means of a Pulsair 2000 NCT (Keeler Instruments, Inc., Broomhall, Pennsylvania) by 5 investigators were evaluated. Three consecutive measurements were taken first on the right eye and then on the left eye in each subject. Topical anesthesia was not used. RESULTS: The distribution of the measured IOP values was significantly different from a normal distribution. The median IOP was 15.0 mmHg (lower quartile/ upper quartile 12.5/17.2). There were no differences in IOP values between male and female subjects or between right and left eyes. There was no correlation between age and IOP values. Ninety percent of the subjects had an IOP within a range of 9-24 mmHg in both eyes. Among the examined subjects, the IOP was above 24 and 21 mmHg in 4,6 and 11%, respectively, in at least one eye. The median range of consecutive IOP measurements in one eye was 3 mmHg (lower quartile/upper quartile 2.0/4.0). The median interocular IOP difference was 1.7 mmHg (0.7/2.7). The median individual coefficient of variation (CV) values were 10.0% for the right eyes, -10.8% for the left eyes. Among the 5 different examiners, the IOP values, range of 3 consecutive IOP readings in one eye, interocular asymmetry and CV values were statistically comparable. CONCLUSION: The Pulsair 2000 NCT is very simple to use and its handling is mostly independent of the operator. The results of the present investigation might be of some value for future screening programs.

Adolescent↗
PubMed1998

Influence of acquisition parameters on hemodynamic measurements with the Heidelberg Retina Flowmeter at the optic disc.

PURPOSE: The Heidelberg Retina Flowmeter (HRF; Heidelberg Engineering GmbH, Heidelberg, Germany) is a new instrument that determines hemodynamic variables at discrete locations of the retina and the optic disc. The objective of this study was to evaluate the influence of various HRF recording settings on the long-term variability of the HRF parameter. "Flow," computed at the optic nerve head in healthy individuals. METHODS: The authors obtained 2 sets of 5 HRF recordings in 10 healthy individuals (age range, 23-60 years). The HRF recordings were obtained within a scan area of 10 degrees x 2.5 degrees (set 1) and 20 degrees x 5 degrees (set 2). For each set, the HRF recordings were obtained on 5 consecutive days. Respective HRF recordings for both sets were obtained on the same days. On these recordings, the HRF parameter, "Flow," was computed at 3 different regions of interest (temporal superior, temporal inferior, and temporal rim of the optic disc). At all three locations, Flow was computed within windows of measurement of 10 pixels x 10 pixels and 20 pixels x 20 pixels. The effect of larger windows (30 pixels x 30 pixels, 40 pixels x 40 pixels, and 50 pixels x 50 pixels) was tested at the temporal rim of the optic disc. RESULTS: The highest reliability coefficient was reached with a scan area of 20 degrees x 5 degrees at the temporal superior rim of the optic disc (r = 0.93). Within a scan area of 20 degrees x 5 degrees, the size of the user-defined measuring window did not influence the reliability. Two models of analysis of variance disclosed that the only effect on the computed value of Flow that reached statistical significance was that because of the scan area (F = 11.172; p = 0.001). The location of the window of measurement and its size had no statistically significant effect. CONCLUSION: The present results show that the location of the window of measurement has an important effect on the long-term variability of the HRF parameter, Flow. In addition, different scan areas influence significantly the computed values of this parameter.

Adult↗
PubMed1998

Angiotensin II and insulin induce growth of ciliary artery smooth muscle: effects of AT1/AT2 antagonists.

PURPOSE: Abnormal growth of smooth muscle cells (SMCs) in small arteries of the eye is associated with hypertension and diabetes, and the complications that they induce. Migration and proliferation of SMCs into the intima are primary mechanisms involved in neointima formation. In aortic SMCs, angiotensin II (AII)-induced proliferation is inhibited by angiotensin type 1 (AT1) receptor antagonist. However, in small artery SMCs, in particular in the circulation of the eye, the effects of AII on migration and proliferation are unknown. METHODS: The effects of AII (10(-6) to 10(-10) M) on migration and proliferation of growth-arrested SMCs of porcine ciliary arteries were studied in the presence and absence of insulin (5 x 10(-10) M) by assaying DNA synthesis (3H-thymidine incorporation), cell number, and movement of SMCs across the membrane of a modified Boyden chamber. RESULTS: In the absence of insulin, only high concentrations (10(-6) to 10(-8) M) of AII induced DNA synthesis and increased cell number (P < 0.05); however, in the presence of insulin (5 x 10(-10) M), AII induced DNA synthesis and cell number at low concentrations (10(-10) M) and in a concentration-dependent manner (P < 0.05). In contrast to proliferation, AII induced SMC migration in a concentration-dependent manner in the absence of insulin (P < 0.05). The AT1 antagonist CGP48933 (10(-8) to 10(-12) M), but not the AT2 antagonist CGP42112 (10(-8) to 10(-12) M), inhibited AII (10(-8) M)-induced proliferation and migration in a concentration-dependent manner (P < 0.05). CONCLUSIONS: Our results suggest that AII is a potent mitogen for SMCs of ophthalmic arteries, an effect that is enhanced in the presence of insulin, and that it may be an important contributor to structural vascular changes in the ophthalmic circulation in hypertension associated with non-insulin dependent diabetes. The inhibition of AII-induced growth by an AT1 antagonist suggests that these drugs may be important therapeutic tools to prevent structural vascular changes in the ophthalmic vasculature under these conditions.

Angiotensin I↗
PubMed1998

Descriptive information of topographic parameters computed at the optic nerve head with the Heidelberg retina tomograph.

PURPOSE: To analyze the frequency distribution and descriptive information of topometric data obtained with the Heidelberg Retina Tomograph (HRT) in a normal population. METHODS: Topographic measurements of the optic disc were acquired and evaluated using the HRT in 225 subjects between 12 and 90 years of age. After randomly selecting one eye per subject, the frequency distributions, mean values, minima, maxima, and first, fifth, fiftieth, ninety-fifth, and ninety-ninth percentiles were evaluated for topographic parameters computed by the HRT. The influence of age, intraocular pressure (IOP), disc size, and disc shape on optic disc topometric data was analyzed. A principal component analysis of the topometric parameters was performed. The frequency distributions, mean values, minima, maxima, and first, fifth, fiftieth, ninety-fifth, and ninety-ninth percentiles of the interocular difference in topographic parameters were evaluated. RESULTS: All topographic parameters showed a unimodal but not necessarily normal distribution. None of the parameters showed a relevant correlation with age, IOP (in the normal range), and overall shape of the anterior optic nerve, but a few parameters showed a clinically significant correlation with disc size. A principal component analysis identified four relevant factors (optic nerve cup, retinal nerve fiber layer, optic disc size, and optic nerve cup shape) in the entire data set of optic nerve topometric data. The absolute value of all interocular differences in topographic parameters showed an asymmetric but unimodal distribution. CONCLUSION: The mathematical description of the optic nerve cup shape provides information on optic nerve head topography independently from cupping, nerve fiber layer thickness, and disc size. Potentially, quantification of further aspects in optic nerve head topography might improve the discriminatory power of computerized quantitative optic nerve head analysis.

Adolescent↗
PubMed1997

Inverse correlation between endothelin-1-induced peripheral microvascular vasoconstriction and blood pressure in glaucoma patients.

BACKGROUND: The potent vasoconstrictor peptide endothelin-1 has been shown to participate in the control of peripheral vascular tone and in the regulation of ocular perfusion. In glaucoma patients vasospasms and arterial hypotension have been identified as risk factors for the progression of glaucomatous damage, and the regulation of endothelin-1 release is disturbed in some of these patients. The aim of this study was to assess the relationship between resting blood pressure and cutaneous vascular responsiveness to endothelin-1 and phenylephrine in patients with glaucoma and in matched controls. METHODS: In 9 patients with primary open-angle glaucoma (POAG), 7 patients with normal tension glaucoma (NTG), and 16 age- and sex-matched controls, endothelin-1 and phenylephrine responses were assessed in the human forearm microcirculation using laser Doppler flowmetry during intra-arterial drug administration. Blood pressure was measured intra-arterially. RESULTS: In contrast to alpha 1-adrenergic effects, endothelin-1 responses were inversely correlated to both systolic (r2 = 0.27, P = 0.05) and diastolic (r2 = 0.54, P = 0.001) blood pressure in glaucoma patients, whereas there was no such correlation in controls. Patients with lower blood pressure values were more sensitive to the vasoconstrictor effects of endothelin-1. Cutaneous responsiveness to endothelin-1 and phenylephrine was similar in glaucoma patients and in controls. CONCLUSION: These results reveal that glaucoma patients appear to have peripheral microvascular abnormalities which are exhibited as altered responsiveness to endothelin-1. Thus, this study supports the hypothesis that endothelin-1-related microvascular dysfunction may be involved in the pathogenesis of glaucomatous damage.

Adult↗
PubMed1997

Blood-flow velocities of the extraocular vessels in patients with high-tension and normal-tension primary open-angle glaucoma.

PURPOSE: To evaluate blood-flow parameters in three different groups of patients with primary open-angle glaucoma. METHODS: Hemodynamic parameters in the ophthalmic artery, central retinal artery, central retinal vein, and lateral and medial short posterior ciliary arteries were evaluated by color Doppler imaging in 237 patients with primary open-angle glaucoma and 124 age-matched normal control subjects. Group A consisted of 56 patients with primary open-angle glaucoma with treated intraocular pressure higher than 20 mm Hg; group B, of 103 patients with primary open-angle glaucoma with progression of glaucomatous damage despite intraocular pressure of 21 mm Hg or less; and group C, of 78 patients with normal-tension glaucoma. RESULTS: All patients showed a significant decrease in end-diastolic velocities (P < .01) and a significant increase in resistivity index (P < .05) in all arteries measured. Peak-systolic velocities were normal in the ophthalmic artery in all three groups. In the central retinal artery and the short posterior ciliary arteries, however, patients in groups B and C had significantly reduced peak-systolic velocity (P < .05) compared with normal control subjects. Peak-systolic velocity in group A did not differ significantly from that of normal control subjects. Maximal and minimal blood-flow velocities in the central retinal vein were significantly lower in groups B and C (P < .001) compared with normal control subjects. In group A, only minimal blood-flow velocity was significantly reduced (P < .05). CONCLUSIONS: Hemodynamic parameters in the extraocular vessels are altered in patients with glaucoma. Reduced blood-flow velocities may be secondary as well as contributory to glaucomatous damage.

Aged↗
PubMed1997

Amlodipine and benazeprilat differently affect the responses to endothelin-1 and bradykinin in porcine ciliary arteries: effects of a low and high dose combination.

PURPOSE: Visual field defects caused by vasospasm are often encountered in ophthalmology as a feature of glaucoma with poor response to conventional treatment. Combination therapy with drugs acting via different mechanisms might be more effective. Therefore, the effects of the calcium antagonist amlodipine and the angiotensin converting enzyme (ACE) inhibitor benazeprilat at low and high dose combination on contractions to endothelin-1 and endothelium-dependent relaxations to bradykinin were examined in porcine ciliary arteries. METHODS: Segments of the arteries were suspended in myographs for isometric tension recording. RESULTS: Pretreatment of the vessels with either amlodipine, the low or high dose combination significantly reduced the sensitivity to endothelin-1 as compared to control (concentration shift 18.3-fold, 14.2-fold, 23.3-fold respectively; p < 0.05), while benazeprilat was ineffective. The maximal response to endothelin-1 (10(-7) M) was most inhibited by the high dose combination which reduced the contractions by 49% as compared to control (p < 0.05). The low dose combination and amlodipine alone were less effective (reduction: 25%; p < 0.05 and 20%; n.s., respectively). On the other hand, benazeprilat enhanced the sensitivity (concentration shift 73-fold; p < 0.05) and maximal relaxation to bradykinin (by 27%; p < 0.01), whereas amlodipine or the low or high dose combination were ineffective. CONCLUSIONS: These findings indicate that amlodipine and benazeprilat differently affect vascular function of ciliary arteries. A high dose combination of both substances was most effective in inhibiting contractions to endothelin-1, suggesting a potentiating effect of the two compounds. In contrast, endothelium-dependent relaxations to bradykinin were enhanced by benazeprilat alone, but not when combined with amlodipine.

Amlodipine↗
PubMed1997

The logic of prevention of glaucomatous damage progression.

Glaucoma is an optic nerve head neuropathy for which there is presently no curative treatment. However, as glaucoma is known to be statistically associated with some risk factors, the logic of glaucomatous damage prevention consists of identifying those risk factors for which a potential therapy is available.

Animals↗
PubMed1997

Blood flow velocity in the extraocular vessels in chronic smokers.

AIMS: To determine blood flow velocity in the extraocular vessels in healthy, chronic smokers and to compare these blood flow velocities with those of healthy non-smokers. METHODS: In 46 healthy chronic smokers and 189 healthy non-smokers, peak systolic velocity (PSV), end diastolic velocity (EDV), and the resistivity index (RI) were measured in the ophthalmic artery (OA), central retinal artery (CRA), lateral short posterior ciliary artery (LPCA), and medial short posterior ciliary artery (MPCA) by means of a colour Doppler device, Siemens Quantum 2000. The maximal (max) and minimal (min) velocities were measured in the central retinal vein (CRV). Only one eye was measured in each subject, and right and left eyes were chosen randomly. Blood flow velocities were compared with one way MANOVA and t tests. The influence of age, sex, systolic and diastolic blood pressure, as well as heart rate on blood flow velocity and RI were evaluated by an analysis of covariance. The potential differences of the influence of the covariables on blood flow variables in smokers and non-smokers were tested by calculating the interactions. RESULTS: In the majority of measured vessels blood flow velocity was higher in smokers than in non-smokers. This difference was statistically significant in the OA, CRV, and LPCA. The RI indices were equal or slightly lower in smokers. Furthermore, smokers had significantly lower systolic and diastolic blood pressure. Heart rate was higher in smokers but this difference did not reach statistical significance. CONCLUSIONS: Colour Doppler measurements may differ significantly in smokers compared with non-smokers. Therefore, smoking habits should be considered when interpreting colour Doppler imaging results, and comparing different groups of diseased or healthy subjects.

Adolescent↗
PubMed1997

Relaxation by bradykinin in porcine ciliary artery. Role of nitric oxide and K(+)-channels.

PURPOSE: To assess the effects of K(+)-channel blockers on bradykinin-induced relaxations in porcine ciliary artery. METHODS: Vascular isometric forces were measured with a myograph system. Ciliary vascular rings were precontracted with thromboxane A2 analog (U 46619, 10(-7) M) to assess dose-dependent (10(-10)-3 x 10(-6) M) bradykinin-induced relaxation after addition of one of the following: the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) or inactive enantiomer (D-NAME, 10(-4) M); the nonspecific K(+)-channel blocker tetra-ethylammonium (TEA, 10(-2) M); or the ATP-sensitive K(+)-channel blocker glibenclamide (10(-5) M). The effect of TEA on relaxations to the NO donor, sodium nitroprusside (SNP, 10(-10)-10(-4) M) was investigated. The membrane potential of vascular smooth muscle cells (VSMC) was recorded after exposure to bradykinin (2.5 x 10(-7) M). RESULTS: Endothelium-dependent relaxations to bradykinin (maximal [max], 99% +/- 3%) were strongly inhibited by L-NAME (max, 39% +/- 4%, P < 0.01) and partially by TEA (max, 62% +/- 3%, P < 0.01) or glibenclamide (max, 77% +/- 4%, P < 0.01). Administration of glibenclamide plus L-NAME further suppressed bradykinin-induced relaxation (max, 23% +/- 6%; P < 0.01), whereas TEA and L-NAME (max, 6% +/- 2%; P < 0.01) abolished the relaxation. SNP relaxations were unaffected by TEA. Bradykinin had no effect on the membrane potential of VSMC. CONCLUSIONS: In porcine ciliary artery, the endothelium-dependent relaxations to bradykinin are primarily mediated by NO and involve K(+)-channels. As only relaxations to bradykinin, but not those mediated by SNP, were inhibited by TEA, this implies that K(+)-channel blockers most likely affect the bradykinin-evoked NO production or release by the endothelium.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗