Effect of the α(2)-adrenoceptor antagonist yohimbine on vascular regulation of the middle cerebral artery and the ophthalmic artery in healthy subjects.

There is evidence that vascular beds distal to the ophthalmic artery (OA) show vasoconstriction in response to a step decrease in systemic blood pressure (BP). The mediators of this response are mostly unidentified. The aim of the current study was to test the hypothesis that α2-adrenoreceptors may contribute to the regulatory process in response to a decrease in BP. In this randomized, double-masked, placebo-controlled study 14 healthy male volunteers received either 22mg yohimbine hydrochloride or placebo. Beat-to-beat BP was measured by analysis of arterial pressure waveform; blood flow velocities in the middle cerebral artery (MCA) and the OA were measured with Doppler ultrasound. Measurements were done before, during and after a step decrease in BP. The step decrease in BP was induced by bilateral thigh cuffs at a suprasystolic pressure followed by a rapid cuff deflation. After cuff deflation, BP returned to baseline after 7-8 pulse cycles (PC). Blood velocities in the MCA returned to baseline earlier (4 PC) than BP indicating peripheral vasodilatation. Blood velocities in the OA returned to baseline later (15-20 PC) indicating peripheral vasoconstriction. Yohimbine did not affect the blood velocity response in the MCA, but significantly shortened the time of OA blood velocities to return to baseline values (6-7 PC, p<0.05). In conclusion, our results indicate that yohimbine did not alter the regulatory response in the MCA, but modified the response of vascular beds distal to the OA. This suggests that α2-adrenoceptors play a role in the vasoconstrictor response of the vasculatures distal to the OA.

Pioglitazone does not affect vascular or inflammatory responses after endotoxemia in humans.

PPARgamma agonists have been proposed to exert more than metabolic benefits, particularly by anti-inflammatory mechanisms. We hypothesized that pioglitazone might modulate inflammatory and vascular responses to lipopolysaccharide (LPS). In a placebo-controlled parallel-group study in 18 healthy male subjects, the E. coli endotoxin model of inflammation (20 IU/kg i. v.) was employed to test the effect of 60 mg pioglitazone over nine days on inflammatory cytokines. Macrovascular function and microvascular blood flow were assessed by brachial artery ultrasound and retinal blood flow parameters, respectively. Pioglitazone increased brachial artery diameter by 5.6% but had no effect on other outcome parameters under resting conditions. LPS increased cytokine levels to peak concentrations of 91.3+/-22.5 ng/ml (IL-6), 261.4+/-60.0 ng/ml (TNFalpha), and 524.5+/-15.3 ng/ml (VCAM-1). The endotoxin caused microvascular vasodilation and increased retinal white blood cell flux, while baseline brachial artery diameter remained unchanged. Pioglitazone had no effect on inflammatory cytokine or adhesion molecule release but mitigated LPS-induced hypotension (p<0.05). Neither brachial artery function nor microvascular blood flow was altered by pioglitazone. In conclusion, acute immune reactions to LPS are not affected by pioglitazone, which exerts subtle vascular effects alone and during endotoxemia. The anti-inflammatory properties of short-term pioglitazone to endotoxins in healthy subjects are therefore limited.

C-reactive protein is expressed and secreted by peripheral blood mononuclear cells.

C-reactive protein (CRP) protects against bacterial pathogens and is a predictor of cardiovascular events. CRP is produced by vascular and organ-specific cells but the generation of CRP from peripheral blood mononuclear cells (PBMC) is poorly established. In a randomized, double-blind, placebo-controlled, two-way cross-over trial six healthy volunteers received a bolus infusion of 20 IU/kg Escherichia coli endotoxin [lipopolysaccharide (LPS)] or placebo. Intracellular CRP protein and CRP secretion of peripheral blood mononuclear cells (PBMC) was measured at baseline and 6 h after LPS by flow cytometry and enzyme-linked immubosorbent assay (ELISA), respectively. CRP mRNA expression was determined by real-time polymerase chain reaction (PCR). Regulation of the expression pathway was assessed using specific inhibitors in vitro. Small amounts of CRP protein and mRNA were detectable in PBMC, which were up-regulated between two- and eightfold by endotoxaemia in vivo. Augmented expression and release of CRP by LPS was consistent in PBMC cell culture experiments. LPS, interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-alpha increased and IL-10 reduced CRP expression in PBMC. Toll-like receptor (TLR)-4, nuclear factor (NF)-kappaB and protein kinase C (PKC) activation were identified as intracellular signal transduction pathways of LPS-induced CRP expression. Constitutive CRP expression and release in PBMC is enhanced by inflammatory stimuli in vivo and in vitro. LPS might induce CRP generation via activation of TLR-4, NF-kappaB and PKC.

Effect of dorzolamide and timolol on ocular blood flow in patients with primary open angle glaucoma and ocular hypertension.

BACKGROUND: There is evidence that perfusion abnormalities of the optic nerve head are involved in the pathogenesis of glaucoma. There is therefore considerable interest in the effects of topical antiglaucoma drugs on ocular blood flow. A study was undertaken to compare the ocular haemodynamic effects of dorzolamide and timolol in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT). METHODS: One hundred and forty patients with POAG or OHT were included in a controlled, randomised, double blind study in two parallel groups; 70 were randomised to receive timolol and 70 to receive dorzolamide for a period of 6 months. Subjects whose intraocular pressure (IOP) did not respond to either of the two drugs were switched to the alternative treatment after 2 weeks. Scanning laser Doppler flowmetry was used to measure blood flow in the temporal neuroretinal rim and the cup of the optic nerve head. Pulsatile choroidal blood flow was assessed using laser interferometric measurement of fundus pulsation amplitude. RESULTS: Five patients did not respond to timolol and were changed to the dorzolamide group, and 18 patients changed from dorzolamide treatment to timolol. The effects of both drugs on IOP and ocular perfusion pressure were comparable. Dorzolamide, but not timolol, increased blood flow in the temporal neuroretinal rim (8.5 (1.6)%, p<0.001 versus timolol) and the cup of the optic nerve head (13.5 (2.5)%, p<0.001 versus timolol), and fundus pulsation amplitude (8.9 (1.3)%, p<0.001 versus timolol). CONCLUSIONS: This study indicates augmented blood flow in the optic nerve head and choroid after 6 months of treatment with dorzolamide, but not with timolol. It remains to be established whether this effect can help to reduce visual field loss in patients with glaucoma.

Effect of a nifedipine induced reduction in blood pressure on the association between ocular pulse amplitude and ocular fundus pulsation amplitude in systemic hypertension.

BACKGROUND: The ocular pressure/volume relation, which is described by the Friedenwald equation, forms the basis of intraocular pressure (IOP) measurement with Schiotz tonometry and measurement of pulsatile ocular blood flow (POBF) with pneumotonometry. Changes in intraocular volume during the cardiac cycle are caused by arterial inflow and venous outflow and are accompanied by changes in IOP. The relation between volume and pressure changes is dependent on the elastic properties of the eye coats as described by the ocular rigidity coefficient. Previous studies indicate that there is a vascular contribution to ocular rigidity and that the volume/pressure relationship may depend on the mean arterial pressure. METHODS: The effect of a nifedipine induced reduction in systemic blood pressure on pulse amplitude (PA) as assessed with pneumotonometry and fundus pulsation amplitude (FPA), as measured with laser interferometry was investigated in 16 untreated patients with moderate to severe systemic hypertension (mean arterial pressure 123 (SD 12) mm Hg). RESULTS: The ratio between PA and FPA was taken as a measure of the ocular rigidity coefficient. Nifedipine reduced mean arterial pressure by 17.3% and increased pulse rate by 11.0% (p<0.001 each). Whereas PA was significantly reduced after administration of nifedipine (-15.6%; p<0.001), FPA remained unchanged. Accordingly, the ratio of PA/FPA was reduced from 0.86 mm Hg/mum to 0.73 mm Hg/mum after administration of nifedipine. CONCLUSION: These data are in keeping with previous animal experiments indicating a blood pressure dependent vascular component to the rigidity of the eye coats in vivo. This needs to be taken into account for measurement of IOP with Schiotz tonometry and POBF with pneumotonometry.

Anterior capsule opacification and lens epithelial outgrowth on the intraocular lens surface after curettage.

PURPOSE: To evaluate the long-term difference in lens epithelial cell (LEC) outgrowth on the anterior surface of a hydrogel intraocular lens (IOL) after curettage of the entire or one half of the circumference of the anterior capsule. SETTING: Department of Ophthalmology, University of Vienna, Austria. METHODS: Forty eyes with senile cataract only were randomly assigned to Group A, which had curettage of the entire anterior capsule, or Group B, which had curettage of the nasal half of the anterior capsule. Rentsch capsule curettes (Geuder) were used, a straight one for the nasal half and a bent model for the temporal half. One surgeon performed all standardized procedures with a temporal clear corneal incision, phacoemulsification, and in-the-bag implantation of a hydrogel IOL. Two years after surgery, the anterior surface of the IOL was examined by specular microscopy in a double-blinded fashion, and LEC outgrowth was graded semiquantitatively. Anterior capsule opacification (ACO) was also graded semiquantitatively. RESULTS: In Group A, grade 2 ACO was observed in 53% of patients and grade 1 ACO in 47%. Similar results were achieved in Group B (59% and 41%, respectively). Two years after IOL implantation, the typically circumferential monolayer outgrowth of LECs on the hydrogel IOL surface was present in 80% in Group A and 60% in Group B. The ongrowth was less dense in the other IOLs; however, no significant differences between the groups were observed. CONCLUSIONS: Mechanical removal of residual LECs with a Rentsch capsule curette from the entire or from one half of the anterior capsule did not reduce LEC outgrowth 2 years after IOL implantation. Furthermore, the ACO grade was not significantly different. Lens epithelial cell proliferation in the germinative region and consecutive migration might be the cause of this outgrowth.

Comparison of the biocompatibility of 2 foldable intraocular lenses with sharp optic edges.

PURPOSE: To compare the clinical performance of 2 foldable intraocular lenses (IOLs) with sharp optic edges in terms of uveal and capsular biocompatibility. SETTING: Department of Ophthalmology, University Hospital of Vienna, Vienna, Austria. METHODS: Fifty eyes scheduled for cataract surgery were included in this comparative study. A standardized surgical protocol was used, and all operations were performed by 1 experienced surgeon. Two posterior chamber lens types of similar design with a 6.0 mm sharp-edged optic and poly(methyl methacrylate) haptics were used. Twenty-five eyes received an AcrySof acrylic IOL (Alcon), and 25 eyes received a CeeOn 911A silicone IOL (Pharmacia). Relevant data were collected at a 3-year follow-up examination. To evaluate uveal biocompatibility, anterior chamber laser flare and cell measurements and inflammatory cell reactions were monitored. Cellular biocompatibility was investigated by examining anterior capsule opacification (ACO), posterior capsule opacification (PCO), and lens epithelial cell (LEC) ongrowth on the IOL's anterior surface. Factors such as intralenticular glistenings and IOL decentration were also evaluated. RESULTS: Anterior chamber flare and cells and the inflammatory cell reaction were significantly lower in the CeeOn 911A group. There was no statistically significant difference in ACO, PCO, and LEC ongrowth between the 2 groups. The AcrySof lenses showed significantly better centration and a higher density of intralenticular glistening. CONCLUSIONS: The findings show that a sharp-edged optic design is, to date, the most effective method of reducing the rate of PCO. Despite a subclinical foreign-body reaction in the AcrySof group, both lenses had a high degree of capsular and uveal biocompatibility.

Postoperative inflammation after lens epithelial cell removal: 2 year results.

PURPOSE: To evaluate the influence on postoperative inflammation of lens epithelial cell (LEC) removal after phacoemulsification. SETTING: Department of Ophthalmology, University of Vienna, Vienna, Austria. METHODS: This randomized prospective single-surgeon study comprised 60 patients with senile cataract only. After a temporal clear corneal incision was made and phacoemulsification performed, no LECs were removed in Group A, LECs in the nasal half were removed in Group B, and LECs were removed from the entire anterior capsule in Group C. The LECs were removed with a Rentsch capsule curette (Geuder). In all eyes, a foldable hydrogel intraocular lens (Hydroview, Bausch & Lomb) was implanted. Anterior chamber flare was evaluated through dilated pupils in a double-masked fashion using a Kowa FC-1000 laser flare-cell meter (LFCM). Measurements were done preoperatively as well as 1, 3, 7, 14, and 28 days and 3, 6, 12, and 24 months postoperatively. RESULTS: In all 3 groups, the flare and cell values increased on the first postoperative day followed by a successive decrease thereafter. One month after surgery, the blood-aqueous barrier (BAB) was nearly restored in all groups. Between the first and fourth week, the flare values in Groups B and C were slightly lower than in Group A; however, mean flare and cell values among groups were not statistically significantly different at any measurement. CONCLUSION: The removal of LECs from the anterior capsule with a Rentsch curette did not influence postoperative BAB changes detected using an LFCM.

[Effect of duration of phacoemulsification on postoperative inflammation--a retrospective study]. / Einfluss der Dauer der Phakoemulsifikation auf die postoperative Inflammation--eine retrospektive Studie.

BACKGROUND: The early postoperative inflammation after cataract surgery is mainly caused by surgical trauma. PATIENTS AND METHODS: 450 data-sheets of patients, who were operated for senile cataract with small-incision phacoemulsification and in-the-bag implantation of a foldable intraocular lens were retrospectively analysed. Postoperative inflammation was evaluated with the Laser Flare-Cell Meter Kowa FC-1000 on day 1, 3, 7 and 28. All the operations were done with the same phacomachine model Orbit Oertli. The absolute phacotime was measured, the data classified in steps of 20 seconds. Statistical analysis was made with the student's t-test. RESULTS: In the first postoperative week there is a statistical significant difference in the flare-values between the groups with short phacotime (up to 39 seconds) and the group with long phacotimes (over 80 seconds). One month after operation this significance was absent. CONCLUSIONS: The early postoperative inflammation is influenced by the duration of phacoemulsification. Surgical techniques and phacomachines that may reduce phacotime are helpful with respect to early postoperative inflammation.

Lens epithelial cell outgrowth on 3 types of intraocular lenses.

PURPOSE: To compare the outgrowth of lens epithelial cells (LECs) on 3 types of intraocular lenses (IOLs) to determine the influence of lens material and lens design (optic edge) on this phenomenon. SETTING: Department of Ophthalmology, University of Vienna, Medical School, Vienna, Austria. METHOD: Ninety eyes scheduled for cataract surgery were included in a prospective comparative study. A standardized surgical procedure was performed by 1 experienced surgeon. Patients received 1 of 3 types of posterior chamber IOLs of similar design with a 6.0 mm optic and poly(methyl methacrylate) haptic: AcrySof (Alcon), HydroView (Bausch & Lomb), or Sensar (Allergan). Each IOL type was implanted in 30 eyes. Postoperative biomicroscopic examinations were performed 1, 3, 7, 30, 90, and 180 days and 1 year after surgery. Lens epithelial cells in each quadrant of the anterior lens surface were subjectively graded. The product with the highest density and the number of quadrants with this density were used to measure LEC outgrowth. RESULTS: Statistically significant differences (P <.05) were seen between the hydrophilic IOL and the 2 hydrophobic lenses from day 30 until the final examination. The HydroView lens had a higher number of LECs on its anterior surface than the AcrySof or Sensar IOL. There were no statistically significant differences between the 2 acrylic IOLs at any measurement. CONCLUSION: The findings suggest that lens surface properties have a greater influence on LEC outgrowth than lens design (ie, sharp optic edge).