Biomedical subjects

Leopold Schmetterer

Publications and source records attributed to Leopold Schmetterer.

At least 19 recordsLinked to original sources

PubMed2006

Influence of infusion volume on the ocular hemodynamic effects of peribulbar anesthesia.

PURPOSE: To test the hypothesis that ocular blood-flow response to peribulbar anesthesia can be reduced by using a smaller volume of anesthetic mixture. SETTING: Departments of Ophthalmology and Clinical Pharmacology, Medical University of Vienna, Vienna, Austria. METHODS: Twenty patients scheduled for bilateral age-related cataract surgery were enrolled in a prospective randomized balanced observer-masked crossover study. Two study days with a 2 mL injection volume or 5 mL injection volume used for peribulbar anesthesia were scheduled. On 1 study day, patients received the 1-dose regimen and on the other study day, when the contralateral eye had surgery, patients received the other injection volume. On both study days, the anesthetic mixture consisted of an equal amount of lidocaine, bupivacaine, and hyaluronidase independently of the injection volume. Intraocular pressure (IOP), blood pressure, and pulse rate were measured noninvasively. Ocular fundus pulsation amplitude (FPA) and peak systolic and end diastolic flow velocities in the central retinal artery were measured with laser interferometry and color Doppler imaging, respectively. The results were recorded as means +/- SD. RESULTS: Peribulbar anesthesia increased IOP and reduced FPA and flow velocities in the central retinal artery. The effects on IOP (5 mL, 35.1% +/- 16.0%; 2 mL, 14.1% +/- 14.1%; P<.001) and ocular hemodynamic parameters (FPA: 5 mL, -17.5% +/- 7.8%/2 mL, -7.3% +/- 7.2%, P<.001; peak systolic velocity: 5 mL, -19.5% +/- 10.7%/2 mL, -10.6% +/- 9.8%, P = .013; end diastolic velocity: 5 mL, -16.7% +/- 6.2%/2 mL, -8.4% +/- 7.3%, P = .005) were more pronounced with the 5 mL injection volume than with the 2 mL injection volume. CONCLUSIONS: An injection volume of 2 mL instead of 5 mL reduced the ocular blood-flow response to peribulbar anesthesia. This procedure may be used in patients with ocular vascular disease to reduce the incidence of anesthesia-induced ischemia and loss of vision.

Aged↗

PubMed2006

Intravenous administration of diphenhydramine reduces histamine-induced vasodilator effects in the retina and choroid.

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

Adult↗

PubMed2006

C-peptide does not affect ocular blood flow in patients with type 1 diabetes.

OBJECTIVE: The aim of the present study was to investigate the effect of intravenous C-peptide infusion on ocular blood flow in patients with type 1 diabetes under euglycemic conditions. RESEARCH DESIGN AND METHODS: The study was performed in a randomized, placebo-controlled, double-masked, two-way, crossover design in 10 type 1 diabetic patients. C-peptide was intravenously administered at two different dosages (dosage 1: 25 pmol . kg(-1) . min(-1) bolus followed by 5 pmol . kg(-1) . min(-1) continuous infusion; dosage 2: six times higher than dosage 1), each for 60 min. Physiologic saline solution was used as a control for C-peptide on a different study day. On both study days, euglycemic clamps were performed. To assess retinal blood flow, laser Doppler velocimetry (blood flow velocities) and retinal vessel analyzer (vessels diameters) measurements were performed. Laser interferometric measurements of fundus pulsation were used to assess pulsatile choroidal blood flow. Blood velocities in the ophthalmic artery were measured using color Doppler imaging. RESULTS: Eight patients (two female and six male) completed the study according to the protocol and without adverse events. One patient developed an anaphylactic reaction to C-peptide, which resolved without sequelae. The following results originate from the remaining eight subjects. Systemic hemodynamic parameters remained stable during both study days. Infusion of C-peptide did not affect any ocular hemodynamic parameter. CONCLUSIONS: The data of the present study indicate that exogenous C-peptide exerts no effect on ocular hemodynamic parameters in type 1 diabetic patients under euglycemic conditions. The maximum detectable change in these parameters was <25%.

Adult↗

PubMed2005

ETa-receptor blockade, but not ACE inhibition, blunts retinal vessel response during isometric exercise.

Angiotensin II and endothelin-1 are potent vasoconstrictors that appear to play a role in retinal blood flow regulation. In the present study, we investigated the possible role of the angiotensin and the endothelin system in the regulation of retinal vessel diameters during isometric exercise in healthy humans. The study design was randomized, double-masked, placebo-controlled, and three-way cross over. Twelve healthy subjects performed squatting exercises for 6 min during infusion of either an angiotensin-converting enzyme inhibitor (enalapril), an ET(A)-receptor antagonist (BQ-123), or placebo. Retinal vessel diameters were measured continuously with the Zeiss retinal vessel analyzer. Systemic hemodynamics were assessed noninvasively, and intraocular pressure was measured with applanation tonometry. Squatting induced a significant increase in blood pressure and pulse rate, which was paralleled by a vasoconstriction in retinal arteries and veins. Intraocular pressure was only slightly increased during the squatting periods. BQ-123 significantly blunted the exercise-induced decrease in venous (P < 0.01) and arterial (P < 0.02, ANOVA) vessel diameters but had no effect on basal retinal diameters. By contrast, enalapril did neither influence vessel diameter at baseline conditions nor in response to isometric exercise. The data of the present study indicate that retinal vasoconstriction during isometric exercise is modified by ET(A)-receptor blockade, whereas it is not altered by angiotensin-converting enzyme inhibition. Hence, the present data indicate that endothelin-1, but not angiotensin II, is involved in retinal blood flow regulation during isometric exercise.

Adult↗

PubMed2005

Polymorphism of the beta-2 adrenoceptor and IOP lowering potency of topical timolol in healthy subjects.

PURPOSE: Beta-2 adrenoceptor antagonists such as timolol have been used in the treatment of glaucoma for more than 30 years. Several functionally important polymorphisms for the beta-2 receptor have been described. In the present study we hypothesized that a relation between the intraocular pressure (IOP) lowering effect of timolol and beta-2 adrenoceptor polymorphisms may exist. METHODS: A total of 270 healthy nonsmoking subjects were screened and individuals homozygous for the wild beta-2 Adrenoceptor (Arg16/Gln27) and two polymorphisms (Gly16/Gln27 or Gly16/Glu27) were included. In these subjects the IOP lowering effect of timolol was compared. RESULTS: Twenty-four subjects were included in the group Arg16/Gln27, 18 subjects in the group Gly16/Gln27, and 47 subjects in the group Gly16/Glu27. The ocular hypotensive effect of timolol was between 40 and 45% in all groups, but not significantly different between the three study groups (p=0.979). CONCLUSIONS: The present study indicates that the beta-2 adrenoceptor polymorphism does not influence the ocular hypotensive effects of topical beta adrenoceptor antagonists. Accordingly, other factors appear to be responsible for the intersubject variability seen with timolol in glaucoma subjects.

Administration, Topical↗

PubMed2005

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

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

Adult↗

PubMed2005

Response of retinal blood flow to systemic hyperoxia in smokers and nonsmokers.

BACKGROUND: We investigated the influence of chronic smoking on ocular vascular reactivity during breathing of 100% oxygen. METHODS: Retinal vascular reactivity was tested during inhalation of 100% oxygen over 10 min. The observer-masked two-cohort study was performed in 24 healthy male volunteers (12 smokers and 12 nonsmokers) using the Zeiss Retinal Vessel Analyzer and laser Doppler velocimetry. From these parameters retinal blood flow was calculated. RESULTS: Hyperoxia significantly decreased arterial (smokers: p<0.001 vs baseline; nonsmokers: p=0.003 vs baseline) and venous (smokers: p<0.001 vs baseline; nonsmokers: p<0.001 vs baseline) diameters. This decrease was significantly more pronounced in smokers (arterial diameter: p<0.001, venous diameter: p=0.003). Hyperoxia decreased venous blood flow velocity (smokers: p=0.02 vs baseline; nonsmokers: p<0.001 vs baseline) to a comparable degree (p=0.51). The two groups showed a comparable decrease in retinal blood flow during hyperoxia (smokers: p<0.001 vs baseline; nonsmokers: p<0.001 vs baseline; p=0.76 between groups). The decrease of PCO(2) during inhalation of 100% oxygen was significantly more pronounced in smokers than in nonsmokers (p=0.038). CONCLUSION: The present study indicates an abnormal retinal vascular response to hyperoxia in smokers. Further studies are needed to identify possible neural or humoral factors involved in this shifted vasoconstrictory status in smokers.

Adult↗

PubMed2005

Intravenous administration of L-arginine increases retinal and choroidal blood flow.

PURPOSE: Nitric oxide (NO) is among the most important regulators of ocular perfusion. L-arginine, an amino acid, is the precursor of NO synthesis. The aim of the present study was to determine whether administration of L-arginine affects ocular blood flow. DESIGN: L-arginine (1 g/min) or placebo was administered intravenously for 30 minutes in 12 healthy volunteers in a randomized, double-masked, two-way cross-over design. METHODS: Ocular hemodynamics were measured before, in the last 10 minutes of the infusion period, as well as 30 minutes after cessation of the administration. Retinal vessel diameters were measured with a retinal vessel analyzer, red blood cell velocities with bidirectional laser Doppler velocimetry, and pulsatile choroidal blood flow was measured using laser interferometry. RESULTS: L-arginine significantly decreased mean arterial pressure by -8 +/- 5% and -6 +/- 7% at the two time points (P < .01), respectively. Intravenous administration of L-arginine increased choroidal blood flow by +10 +/- 6% and +12 +/- 7%, respectively. Retinal venous diameters decreased by -2.5 +/- 2.1% and -1.4 +/- 2.7%, respectively, whereas red blood cell velocity significantly increased after administration of L-arginine by +22 +/- 23% and +20 +/- 19% at the two time points. Thus, calculated blood flow in retinal veins, increased by +21 +/- 18% and +21 +/- 19% before and after the end of L-arginine infusion. CONCLUSIONS: Intravenous administration of L-arginine increases retinal and choroidal blood flow in healthy volunteers. Whether this effect is related to an increased NO-production or an unidentified mechanism remains to be clarified. However, administration of L-arginine might be an interesting new approach to therapeutically increase ocular blood flow in ocular vascular disease.

Adult↗

PubMed2005

Effects of moderate changes in intraocular pressure on ocular hemodynamics in patients with primary open-angle glaucoma and healthy controls.

PURPOSE: There is some indirect evidence for altered autoregulation in patients with glaucoma, but only a few studies have measured ocular blood flow directly during changes in ocular perfusion pressure. The present study was designed to compare pulsatile choroidal blood flow and optic nerve head (ONH) blood flow during moderate increases in intraocular pressure (IOP) in patients with primary open-angle glaucoma (POAG) and normal controls. DESIGN: Two nonrandomized studies comparing blood flow responses in glaucoma patients and controls in an open design. PARTICIPANTS AND CONTROLS: Sixteen patients with POAG glaucoma and 16 healthy gender-matched and age-matched controls were included in the choroidal blood flow experiments. The ONH blood flow experiment was performed in 14 POAG patients and 14 healthy gender-matched and age-matched controls. METHODS: In the first study, pulsatile choroidal blood flow was assessed by laser interferometric measurement of fundus pulsation amplitude (FPA). In the second study, ONH blood flow was measured using laser Doppler flowmetry. In both cohorts, the IOP was increased stepwise by 10 and 20 mmHg using a suction cup. MAIN OUTCOME MEASURES: Fundus pulsation amplitude and ONH blood flow. RESULTS: The baseline values of FPA and ONH blood flow were lower in glaucoma patients as compared with age-matched and gender-matched healthy controls. In patients with POAG, FPA decreased by -4.5+/-5.8% and -11.3+/-4.9% during elevation of IOP of 10 and 20 mmHg, respectively. These results were not different from the results in healthy controls, where FPA decreased by -5.1+/-3.4% and -12.2+/-4.9% at the 2 pressure levels (P = 0.23 between groups). Optic nerve head blood flow showed no changes during the increase of IOP of 10 and 20 mmHg in either of the 2 groups (glaucoma patients, +2.1+/-14.7% and -0.8+/-15.2%; healthy controls, +4.3+/-12.0% and +0.2+/-14.2%; P = 0.83 between groups). CONCLUSIONS: The present study does not provide evidence for altered autoregulation in patients with POAG during a moderate increase in IOP. However, these results do not necessarily contradict the concept of vascular dysregulation in glaucoma.

Aged↗

PubMed2005

Rofecoxib attenuates both primary and secondary inflammatory hyperalgesia: a randomized, double blinded, placebo controlled crossover trial in the UV-B pain model.

The analysis of drug's influence on peripheral and central sensitisation can give useful information about its mode of action and can lead to more efficacy in the treatment of pain. Peripheral inflammation is associated with peripheral expression and up-regulation of cyclooxygenase 2 (COX-2) in the CNS. The relative contribution of COX-2 mediated central sensitisation may be prominent under inflammatory conditions. In this randomized, double blinded, placebo controlled cross-over trial the effects of multidoses of the COX-2 selective inhibitor rofecoxib on primary and secondary hyperalgesia were evaluated in the UVB pain model. Twenty-four hours after local UVB irradiation at the upper leg of 42 healthy volunteers heat pain perception (HPPT) and heat pain tolerance thresholds (HPTT) were assessed within the inflammation. The area of secondary hyperalgesia was determined by pin prick test. Subjects received oral rofecoxib 50, 250, 500 mg or placebo. Pain testing was repeated after 3 and 6 h. Compared to placebo, rofecoxib significantly increased HPPT (1.55 and 1.08 degrees C, P<0.0001 and P=0.0333), HPTT (1.74 and 1.58 degrees C, P<0.0001 and P<0.0001), and reduced the mean area of secondary hyperalgesia by 15.6% (P=0.007) and 16.8% (P<0.001) after 3 and 6 h. No significant difference between the three dosage groups was observed. These data confirm peripheral effects of rofecoxib in a human inflammatory UV-B pain model and provide circumstantial evidence that even a standard clinical dose of rofecoxib reduces central hyperalgesia in inflammatory pain. We confirm that the effect of single oral dose of rofecoxib plateaus at 50 mg.

Adult↗

PubMed2005

Comparison of the autoregulatory mechanisms between middle cerebral artery and ophthalmic artery after thigh cuff deflation in healthy subjects.

PURPOSE: To compare dynamic autoregulation in the middle cerebral artery (MCA) and the ophthalmic artery (OA) after a step decrease in systemic blood pressure. METHODS: Eighteen healthy male young subjects were studied. Ultrasound parameters and systemic blood pressures were recorded in each subject before, during, and after a step decrease in blood pressure. Continuous blood pressure recordings were made with a finger plethysmograph system, and flow velocities in the MCA and the OA were continuously measured with Doppler ultrasound. Large bilateral thigh cuffs were inflated and a pressure approximately 20 mm Hg above peak systolic blood pressure was maintained for 3 minutes. A decrease in blood pressure was induced by rapid deflation of bilateral thigh cuffs. Experiments were performed separately for the OA and the MCA. RESULTS: Systemic blood pressure showed a step decrease immediately after thigh cuff release (9%-15%) and returned to baseline 7 to 10 pulse cycles later. Flow velocities in the MCA returned to baseline earlier than systemic blood pressure, indicating peripheral vasodilatation, with a maximum of five to six pulse cycles after the blood pressure decrease. By contrast, flow velocities in the OA returned to baseline later than systemic blood pressure, reflecting peripheral vasoconstriction with a maximum 10 to 15 pulse cycles after cuff release. There was a statistically significant difference in the time course of the resistance changes in the two selected arteries after thigh cuff release (P < 0.001). CONCLUSIONS: The results of the present study suggest substantial differences in the autoregulatory behavior of the vascular beds peripheral to the MCA and the OA. Results in the MCA would be compatible with either metabolic or myogenic vasodilatation, whereas the results in the OA could reflect sympathetic vasoconstriction. Further studies are needed to support this hypothesis. The thigh cuff technique may represent an interesting approach to the study of autoregulation in patients with ocular vascular disease.

Adult↗

PubMed2005

Short-term increase of intraocular pressure does not alter the response of retinal and optic nerve head blood flow to flicker stimulation.

PURPOSE: It has been shown that stimulation with diffuse luminance flicker induces vasodilatation in the human retina and increases optic nerve head (ONH) blood flow. The present study was designed to investigate the influence of a short-term increase in intraocular pressure on flicker-induced changes in ONH blood flow and retinal vessel diameters. METHODS: In a group of 15 healthy volunteers, IOP was increased by the episcleral suction cup technique. ONH blood flow was assessed with a laser Doppler flowmeter, and retinal vessel diameters were measured with the retinal vessel analyzer. Flicker responses of retinal vessel diameters and ONH blood flow were determined at baseline conditions and during suction of 70 and 140 mm Hg. Flicker light consisted of 8-Hz square-wave flashes at a wavelength below 550 nm and produced a retinal irradiance of 140 muW/cm(2). RESULTS: Suction increased IOP from 12 +/- 2 to 27 +/- 4 mm Hg and 43 +/- 4 mm Hg. Stimulation with diffuse luminance flicker induced an increase in ONH blood flow of +24.0% +/- 20.7%. Increased IOP did not significantly change the flicker response in the ONH (+19.3% +/- 26.6% and +22.1% +/- 25.1%). In retinal veins, flicker induced an increase in vessel diameter of +3.0% +/- 2.0%. Flicker responses in retinal veins were not significantly altered after the IOP was increased, compared with those recorded at baseline IOP (+2.8% +/- 2.5% and +3.2% +/- 2.2%). The flicker response in retinal arteries at baseline IOP was +3.5% +/- 2.0%. Again, the increase in IOP did not significantly alter this flicker response (+2.8% +/- 1.6% and +3.1% +/- 2.4%). CONCLUSIONS: A short-term increase in IOP does not alter the response of retinal vessel diameters and ONH blood flow to diffuse luminance flicker, which indicates that increased IOP does not alter retinal or ONH regulation during neuronal stimulation.

Blood Flow Velocity↗

PubMed2005

Choroidal hemodynamic changes during isometric exercise in patients with inactive central serous chorioretinopathy.

PURPOSE: Imaging studies suggest that the choroidal vasculature may be altered in central serous chorioretinopathy. Little is known, however, about the regulation of ocular blood flow in patients with central serous chorioretinopathy (CSC). The hypothesis for the present study was that choroidal blood flow changes during an increase in ocular perfusion pressure induced by isometric exercise may be altered in CSC. METHODS: An observer-masked, two-cohort study was performed in 14 nonsmoking patients with chronic-relapsing but inactive CSC and in 14 healthy nonsmoking volunteers. Both groups were matched for age and sex. Subfoveal choroidal blood flow (CBF) was assessed with laser Doppler flowmetry, and ocular perfusion pressure (OPP) was calculated from mean arterial pressure (MAP) and intraocular pressure (IOP). Changes of CBF during isometric exercise over a period of 6 minutes were measured. RESULTS: Whereas the increase of MAP, the pulse rate, and the OPP were comparable between the two study groups, subfoveal CBF increased significantly more in the group of patients with CSC (P < 0.001). IOP remained unchanged in both groups during isometric exercise. At an 85% increase in OPP, subfoveal CBF was approximately twice as high in the patients with CSC compared with the healthy control group. CONCLUSIONS: The data indicate an abnormal subfoveal CBF regulation in patients with relapsing CSC compared with age-matched, nonsmoking, healthy volunteers during isometric exercise.

Adult↗

PubMed2005

Inhaled carbon monoxide increases retinal and choroidal blood flow in healthy humans.

PURPOSE: It has been hypothesized that carbon monoxide (CO) acts as an important vascular paracrine factor and plays a role in blood flow regulation in several tissues. The present study investigated the effect of inhaled CO on retinal and choroidal blood flow. METHODS: Fifteen healthy male volunteers were studied in a randomized, double-masked, placebo-controlled design with washout periods of at least 1 week between study days. CO in a dose of 500 ppm or placebo (synthetic air without CO) was inhaled for 60 minutes. Ocular hemodynamics were measured at baseline and at 30 and 60 minutes after start of inhalation. Retinal vessel diameters were measured with a retinal vessel analyzer. RBC velocity was assessed using bidirectional laser Doppler velocimetry. Retinal blood flow was calculated based on retinal vessel diameters and RBC velocity. Fundus pulsation amplitude (FPA) was measured using laser interferometry, and submacular choroidal blood flow using laser Doppler flowmetry. RESULTS: Breathing of CO significantly increased carboxyhemoglobine, from 1.2 +/- 0.5% to 8.5 +/- 0.9% and 9.4 +/- 0.6% at the two time points, respectively (P < 0.01). The diameter of retinal arteries increased by +3.5 +/- 3.8% and +4.2 +/- 3.9% (P < 0.01) in response to CO inhalation. In retinal veins, CO also induced an increase in diameter of +4.3 +/- 3.0% and +4.8 +/- 5.0%, respectively (P < 0.01). By contrast, placebo did not influence retinal vessel diameter. RBC velocity tended to increase during CO inhalation (+8 +/- 22%), but this effect did not reach the level of significance (P = 0.1). Calculated retinal blood flow increased significantly by +12 +/- 5% (P < 0.02). FPA increased after breathing CO by +20 +/- 20% and +26 +/- 21% at the two time points, respectively (P < 0.01). Subfoveal choroidal blood flow increased by +14 +/- 9% and +15 +/- 9% during breathing of CO (P < 0.01). CONCLUSIONS: This experiment demonstrated that retinal and choroidal blood flow increase during inhalation of CO. Whether this increase is caused by tissue hypoxia or a yet unknown mechanism has to be clarified.

Administration, Inhalation↗

PubMed2005

Effect of information on reported adverse events in a placebo-controlled trial.

OBJECTIVE: Although placebo controls are a standard measure in clinical trials the mechanisms underlying placebo effects are still not fully understood. We hypothesised that information about the likelihood of receiving placebo might influence the perception of adverse effects in volunteers participating in a clinical trial. METHODS: Healthy subjects received either nifedipine 20 mg or placebo in an adaptive two-stage crossover study. Sixty subjects were randomised to a group given either correct (50% chance) or misleading (100% chance) information about the likelihood of receiving the active drug. A sum of the severity scores from visual analogue scales over all individual adverse effects was defined as the primary endpoint. RESULTS: The analysis revealed no difference in the primary endpoint between the two groups. This lack of difference may in part be attributable to a conditioning effect as on the first study day higher symptom scores were reported by the participants than on the second study day. Furthermore, the day effect seemed to arise mainly when the first day treatment was the placebo. For the placebo the day effect was clearly significant (p = 0.012), with higher scores on the first day. A further explorative finding in patients given placebo was a tendency for higher scores in the group with the misleading information (p = 0.08). Nothing of that sort was found in the analysis for active treatment. The day effect collapsed and the factor information did not show any tendency of being a potential influence. CONCLUSIONS: In the present study we did not find a statistically significant effect of misleading information on reported adverse events. The large treatment and day effects observed made it difficult to detect a potential small information effect. However, this study excluded a strong and relevant effect of information on the frequency and severity of reported adverse events.

Adult↗

PubMed2004

LPS-induced microvascular leukocytosis can be assessed by blue-field entoptic phenomenon.

Administration of low doses of Escherichia coli endotoxin [a lipopolysaccharide (LPS)] to humans enables the study of inflammatory mechanisms. The purpose of the present study was to investigate whether the blue-field entoptic technique may be used to quantify the increase in circulating leukocytes in the ocular microvasculature after LPS infusion. In addition, combined laser Doppler velocimetry and retinal vessel size measurement were used to study red blood cell movement. Twelve healthy male volunteers received 20 IU/kg iv LPS as a bolus infusion. Outcome parameters were measured at baseline and 4 h after LPS administration. In the first protocol (n = 6 subjects), ocular hemodynamic effects were assessed with the blue-field entoptic technique, the retinal vessel analyzer, and laser Doppler velocimetry. In the second protocol (n = 6 subjects), white blood cell (WBC) counts from peripheral blood samples and blue-field entoptic technique measurements were performed. LPS caused peripheral blood leukocytosis and increased WBC density in ocular microvessels (by 49%; P = 0.036) but did not change WBC velocity. In addition, retinal venous diameter was increased (by 9%; P = 0.008), but red blood cell velocity remained unchanged. The LPS-induced changes in retinal WBC density and leukocyte counts were significantly correlated (r = 0.87). The present study indicates that the blue-field entoptic technique can be used to assess microvascular leukocyte recruitment in vivo. In addition, our data indicate retinal venous dilation in response to endotoxin.

Adult↗

PubMed2004

Specific endothelin ET(A) receptor antagonism does not modulate insulin-induced hemodynamic effects in the human kidney, eye, or forearm.

There is evidence that hyperinsulinemia may stimulate endothelin-1 (ET-1) generation or release, which may affect diabetic vascular complications. BQ-123, a specific ET(A) receptor antagonist, was used to investigate if insulin-induced vascular effects are influenced by an acute ET-1 release. Two randomized, placebo-controlled, double-blind, cross-over studies were performed. In protocol 1, 12 healthy subjects received, on separate study days, infusions of BQ-123 (60 microg/min for 30 min) during placebo clamp conditions, BQ-123 during euglycemic hyperinsulinemia (3 mU/kg/min for 390 min), or placebo during euglycemic hyperinsulinemia. Fundus pulsation amplitude (FPA) was measured to assess pulsatile choroidal blood flow, and mean flow velocity (MFV) of the ophtalmic artery was measured by color Doppler imaging. In protocol 2, eight healthy subjects received, on separate study days, intra-arterial infusions of BQ-123 (32 microg/min for 120 min) during placebo or insulin clamp. Forearm blood flow was measured with bilateral plethysmography, expressing the ratio of responses in the intervention arm and in the control arm. Insulin alone increased FPA (+10%, p < 0.001) and forearm blood flow (+19%). BQ-123 increased FPA, MFV, and forearm blood flow ratio in the absence and presence of exogenous insulin, but this effect was not different between normo- and hyperinsulinemic conditions. ET-1 plasma concentrations were not affected by insulin. In conclusion, these data do not support the concept that hyperinsulinemia increases ET-1 generation in healthy subjects. Our results, however, cannot necessarily be extrapolated to diabetic and obese subjects.

Adult↗

PubMed2004

Real-time measurement of in vitro flow by Fourier-domain color Doppler optical coherence tomography.

The possibility of measuring a full Doppler flow depth profile in parallel by use of frequency-domain optical coherence tomography is demonstrated. The method is based on a local phase analysis of the backscattered signal and allows for imaging of bidirectional Doppler flow. The Doppler frequency limit is 5 kHz for the presented measurements and is set by half of the frame rate of the CCD detector array. We measured the flow of 0.3-microm microspheres suspended in distilled water at controlled flow rates and in vitro human blood flow through a 200-microm capillary with a real-time color-encoded Doppler tomogram rate of 2-3/s.

Blood Cells↗