RESUMO
Overload-induced heart failure is associated with enhanced apoptosis of cardiomyocytes, and increased mechanical load is an inductor of this apoptosis. It is unknown whether nebivolol, a third generation beta(1)-adrenoceptor antagonist, possesses properties that can attenuate this apoptosis. Multicellular preparations from rabbit hearts were mounted in a culture system that allows for measurement of contractile parameters over several days. Culturing these muscles on a constant high preload induces apoptosis of the cardiomyocytes. Of each heart, 1 preloaded muscle preparation was treated with nebivolol (10(-6) mol/l), 1 preloaded without continuous exposure to nebivolol (positive control) and 1 unloaded (negative control). After 48 h of continuous loaded contractions, apoptosis was assessed by TUNEL-assay to confirm that nuclei of myocytes were affected, or by DNA-ladder intensity analysis for semiquantification. Maximal twitch force development was slightly, but significantly, lower in preparations contracting in presence of nebivolol (compared to solvent) while twitch-timing parameters were similar. After 48 h of continuous contractions, no additional differences were observed between the groups regarding contractile parameters. DNA-ladder analysis showed a similar rate of apoptosis in presence of nebivolol. Nebivolol does not increase, nor decrease, the rate of load-induced cardiomyocyte apoptosis.
Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Apoptose/efeitos dos fármacos , Benzopiranos/farmacologia , Etanolaminas/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Estresse Mecânico , Animais , DNA/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Feminino , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/patologia , Nebivolol , Coelhos , Técnicas de Cultura de TecidosRESUMO
The implantation of electronic retina stimulators appears to be a future possibility to restore vision, at least partially in patients with retinal degeneration. The idea of such visual prostheses is not new but due to the general technical progress it has become more likely that a functioning implant will be on the market soon. Visual prosthesis may be integrated in the visual system in various places. Thus there are subretinal and epiretinal implants, as well as implants that are connected directly to the optic nerve or the visual cortex. The epiretinal approach is the most promising at the moment, but the problem of appropriate modulation of the image information is unsolved so far. This will be necessary to provide a interpretable visual information to the brain. The present article summarises the concepts and includes some latest information from recent conferences.
Assuntos
Cegueira/reabilitação , Terapia por Estimulação Elétrica/instrumentação , Terapia por Estimulação Elétrica/tendências , Próteses e Implantes/tendências , Terapia Assistida por Computador/instrumentação , Terapia Assistida por Computador/tendências , Terapia por Estimulação Elétrica/métodos , Desenho de Equipamento/tendências , Humanos , Terapia Assistida por Computador/métodosRESUMO
Oxidative stress at the retinal pigment epithelium (RPE) is involved in the pathophysiology of age-related macula degeneration (ARMD). Observations on a clinical or laboratory level have revealed that supplementation of antioxidative scavengers failed in many cases. A potential therapeutic target is the cellular signal transduction cascade initiated by oxidative stress which results, e. g., in altered expression of pro- and antiagiogenic factors as well as induction of apoptosis. This review summarises the current literature on cellular effects of free radicals and deduces potential therapeutic approaches to protect the RPE from oxidative damage.
Assuntos
Antioxidantes/administração & dosagem , Degeneração Macular/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Humanos , Degeneração Macular/tratamento farmacológico , Epitélio Pigmentado da Retina/efeitos dos fármacosRESUMO
BACKGROUND: The intraocular pressure (IOP) lowering effects of deep sclerectomy (partially combined with phacoemulsification) with different scleral implants (T-Flux- or SK-Gel) were investigated. PATIENTS AND METHODS: In a retrospective study, 72 patients with medically uncontrollable glaucoma underwent non-penetrating deep sclerectomy. Of these, 54 patients received T-Flux implants and 18 SK-Gel implants. Examinations were carried out shortly before and after surgery, as well as after 12 months. RESULTS: Prior to surgery IOP was 18.4+/-5.5 mmHg (n=72) and 12 months after surgery it was 13.1+/-3.8 mmHg (n=65). The number of antiglaucomatous eyedrops used prior to surgery was 2.3+/-1.3 (n=72) and 12 months after surgery 0.2+/-0.6 mmHg (n=65). Secondary IOP-lowering surgery after 12 months was carried out on 15.3% of the operated eyes, and consecutive goniopunctures after 12 months were 25%. No significant differences were found between the two groups. CONCLUSIONS: The short- and mid-term IOP lowering effects in deep sclerectomy with scleral implants were quite satisfying no matter which implant was used. There was no difference in deep sclerectomy whether or not combined with cataract surgery.
Assuntos
Implantes Absorvíveis , Glaucoma de Ângulo Fechado/cirurgia , Glaucoma de Ângulo Aberto/cirurgia , Complicações Pós-Operatórias/etiologia , Esclerostomia/instrumentação , Terapia Combinada , Seguimentos , Humanos , Pressão Intraocular , Lentes Intraoculares , Complicações Pós-Operatórias/cirurgia , Reoperação , Estudos RetrospectivosRESUMO
The FK506-binding protein FKBP12.6 is tightly associated with the cardiac sarcoplasmic reticulum (SR) Ca(2+)-release channel (ryanodine receptor type 2 [RyR2]), but the physiological function of FKBP12.6 is unclear. We used adenovirus (Ad)-mediated gene transfer to overexpress FKBP12.6 in adult rabbit cardiomyocytes. Western immunoblot and reverse transcriptase-polymerase chain reaction analysis revealed specific overexpression of FKBP12.6, with unchanged expression of endogenous FKBP12. FKBP12.6-transfected myocytes displayed a significantly higher (21%) fractional shortening (FS) at 48 hours after transfection compared with Ad-GFP-infected control cells (4.8+/-0.2% FS versus 4+/-0.2% FS, respectively; n=79 each; P:=0.001). SR-Ca(2+) uptake rates were monitored in beta-escin-permeabilized myocytes using Fura-2. Ad-FKBP12.6-infected cells showed a statistically significant higher rate of Ca(2+) uptake of 0.8+/-0.09 nmol/s(-)(1)/10(6) cells (n=8, P:<0.05) compared with 0.52+/-0.1 nmol/s(-)(1)/10(6) cells in sham-infected cells (n=8) at a [Ca(2+)] of 1 micromol/L. In the presence of 5 micromol/L ruthenium red to block Ca(2+) efflux via RyR2, SR-Ca(2+) uptake rates were not significantly different between groups. From these measurements, we calculate that SR-Ca(2+) leak through RyR2 is reduced by 53% in FKBP12.6-overexpressing cells. Caffeine-induced contractures were significantly larger in Ad-FKBP12.6-infected myocytes compared with Ad-GFP-infected control cells, indicating a higher SR-Ca(2+) load. Taken together, these data suggest that FKBP12.6 stabilizes the closed conformation state of RyR2. This may reduce diastolic SR-Ca(2+) leak and consequently increase SR-Ca(2+) release and myocyte shortening.
Assuntos
Cálcio/metabolismo , Contração Miocárdica/fisiologia , Miocárdio/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Retículo Sarcoplasmático/metabolismo , Proteínas de Ligação a Tacrolimo/metabolismo , Adenoviridae/genética , Animais , Western Blotting , Cafeína/farmacologia , Células Cultivadas , Técnicas de Transferência de Genes , Contração Miocárdica/efeitos dos fármacos , Contração Miocárdica/genética , Miocárdio/citologia , Isoformas de Proteínas , Coelhos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Rutênio Vermelho/farmacologia , Retículo Sarcoplasmático/efeitos dos fármacos , Sirolimo/farmacologia , Tacrolimo/farmacologia , Proteínas de Ligação a Tacrolimo/genética , TransfecçãoRESUMO
Na(+)-Ca(2+) exchanger (NCX) gene expression is increased in the failing human heart. We investigated the hypothesis that upregulation of NCX can induce depressed contractile performance. Overexpression of NCX was achieved in isolated rabbit ventricular myocytes through adenoviral gene transfer (Ad-NCX). After 48 hours, immunoblots revealed a virus dose-dependent increase in NCX protein. Adenoviral beta-galactosidase transfection served as a control. The fractional shortening (FS) of electrically stimulated myocytes was analyzed. At 60 min(-1), FS was depressed by 15.6% in the Ad-NCX group (n=143) versus the control group (n=163, P:<0.05). Analysis of the shortening-frequency relationship showed a steady increase in FS in the control myocytes (n=26) from 0.027+/-0.002 at 30 min(-1) to 0. 037+/-0.002 at 120 min(-1) (P:<0.05 versus 30 min(-1)) and to 0. 040+/-0.002 at 180 min(-1) (P:<0.05 versus 30 min(-1)). Frequency potentiation of shortening was blunted in NCX-transfected myocytes (n=27). The FS was 0.024+/-0.002 at 30 min(-1), 0.029+/-0.002 at 120 min(-1) (P:<0.05 versus 30 min(-1), P:<0.05 versus control), and 0. 026+/-0.002 at 180 min(-1) (NS versus 30 min(-1), P:<0.05 versus control). Caffeine contractures, which indicate sarcoplasmic reticulum Ca(2+) load, were significantly reduced at 120 min(-1) in NCX-transfected cells. An analysis of postrest behavior showed a decay of FS with longer rest intervals in control cells. Rest decay was significantly higher in the Ad-NCX group; after 120 seconds of rest, FS was 78+/-4% in control and 65+/-3% in the Ad-NCX group (P:<0.05) relative to steady-state FS before rest (100%). In conclusion, the overexpression of NCX in rabbit cardiomyocytes results in the depression of contractile function. This supports the hypothesis that upregulation of NCX can result in systolic myocardial failure.
Assuntos
Contração Miocárdica/fisiologia , Trocador de Sódio e Cálcio/fisiologia , Adenoviridae/genética , Animais , Células Cultivadas , Técnicas de Transferência de Genes , Vetores Genéticos , Ventrículos do Coração/patologia , Humanos , Miocárdio/metabolismo , Coelhos , Trocador de Sódio e Cálcio/genética , Transfecção , Função VentricularRESUMO
BACKGROUND: An altered perfusion of the optic nerve head has been proposed as a pathogenic factor in glaucoma. AIM: To investigate potential differences in the ocular haemodynamics of patients having glaucoma with progressive versus stable disease, as well as healthy volunteers. METHODS: Peak-systolic velocity (PSV), end-diastolic velocity (EDV) and resistivity index in the short posterior ciliary artery (SPCA), central retinal artery (CRA) and ophthalmic artery were recorded in 114 consecutive patients having glaucoma with an intraocular pressure (IOP) < or =21 mm Hg, as well as in 40 healthy volunteers, by colour Doppler imaging (CDI). RESULTS: Of the 114 patients with glaucoma, 12 showed glaucoma progression (follow-up period: mean 295 (standard deviation (SD) (18) days). CDI measurements in these patients showed decreased PSV and EDV in the SPCA (p<0.001 and p<0.05, respectively) and decreased PSV in the CRA compared with patients with stable glaucoma and healthy controls (p<0.05). No differences in flow velocities were found for the ophthalmic artery. IOP and systemic blood pressure was similar in all the three groups. CONCLUSIONS: Progressive glaucoma is associated with decreased blood flow velocities in the small retrobulbar vessels supplying the optic nerve head. The detected difference could represent a risk factor for progression of glaucomatous optic neuropathy.
Assuntos
Artérias Ciliares/fisiopatologia , Glaucoma/fisiopatologia , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Artérias Ciliares/diagnóstico por imagem , Progressão da Doença , Feminino , Seguimentos , Glaucoma/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Oftálmica/diagnóstico por imagem , Artéria Oftálmica/fisiopatologia , Artéria Retiniana/diagnóstico por imagem , Artéria Retiniana/fisiopatologia , Ultrassonografia Doppler em Cores , Acuidade VisualRESUMO
OBJECTIVE: The immunosuppressive drug Cyclosporine A (CsA) is a key substance in pharmacological therapy following solid organ transplantation and has been suggested to prevent cardiac hypertrophy. We investigated the direct effects of CsA on myocardial function, because these are largely unknown. METHODS: In multicellular cardiac muscle preparations from end-stage failing and non-failing human hearts as well as from non-failing rabbit hearts we investigated the effects of CsA on contractile performance, sarcoplasmic reticulum (SR) Ca2+-load, cytosolic calcium transients, calcium sensitivity of the myofilaments, and myocardial oxygen consumption. RESULTS: In failing human muscle preparations there was a concentration dependent decrease in contractile force; the maximal effect amounted to 55.6+/-6.4% of control while EC50 was reached at 1.0+/-0.3 nM (n=6). These concentrations are at and even below the therapeutic plasma levels. CsA decreased the aequorin light signal in human failing trabeculae to 71.5+/-5.9% (n=5), indicating decreased calcium transients. Estimation of the SR calcium load via measurement of rapid cooling contractures revealed a decrease to 84.4+/-6.5% in failing human preparations (n=6). Measurements of both decreased SR calcium load and force development in presence of CsA were also observed in four non-failing human muscle preparations. In rabbit muscle preparations (n=8), developed force decreased to 50.2+/-7.7% (n=8, EC50: 1.9+/-0.4 nM) and rapid cooling contractures to 74.0+/-7.4% of control at 100 nmol/l CsA. No direct effects were observed on myofilament calcium sensitivity nor on maximal force development of permeabilized preparations from the rabbit (n=7). Oxygen consumption measurements showed that CsA decreased the economy of contraction to 76.4+/-7.9% in rabbit preparations (n=8). CONCLUSIONS: CsA causes a direct cardio-depressive effect at clinically relevant concentrations, most likely due to altered handling of Ca2+ by the SR.
Assuntos
Cálcio/metabolismo , Ciclosporina/farmacologia , Imunossupressores/farmacologia , Contração Miocárdica/efeitos dos fármacos , Miocárdio/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Animais , Temperatura Baixa , Depressão Química , Relação Dose-Resposta a Droga , Insuficiência Cardíaca/metabolismo , Humanos , Técnicas In Vitro , Coelhos , Retículo Sarcoplasmático/metabolismoRESUMO
The hydroxyl radical (*OH) is a very reactive oxygen-free radical species that has profound effects on myocardial contractility. We investigated the impact of *OH on free radical induced injury in right ventricular rabbit cardiac trabeculae. Additionally, we investigated the protective properties of the beta-adrenoceptor antagonist nebivolol. The contractile response to a brief, 2 min exposure to *OH consisted of a severe but transient rigor-like contracture, followed by a new steady state in which diastolic force (Fdia) remained increased and developed force (Fdev) remained decreased. In the new steady state sarcoplasmic reticulum function only partly recovered, reflected by a > 50% blunted force-frequency relationship. In the presence of nebivolol (10(-6) M), during the early phase the increase in Fdia was significantly smaller, and recovered better while Fdev was higher during peak. Moreover, nebivolol completely abolished blunting of the force-frequency relationship, which was observed in the sustained *OH injury phase. The results indicate that hydroxyl radical injury induces systolic and diastolic dysfunction, and that nebivolol can effectively prevent a large part of this *OH injury.
Assuntos
Radical Hidroxila/farmacologia , Retículo Sarcoplasmático/efeitos dos fármacos , Agonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Benzopiranos/farmacologia , Relação Dose-Resposta a Droga , Estimulação Elétrica , Etanolaminas/farmacologia , Feminino , Coração/efeitos dos fármacos , Coração/fisiologia , Peróxido de Hidrogênio/farmacologia , Técnicas In Vitro , Isoproterenol/farmacologia , Masculino , Contração Miocárdica/efeitos dos fármacos , Nebivolol , Oxidantes/farmacologia , Coelhos , Retículo Sarcoplasmático/fisiologiaRESUMO
Ca(2+)-sensitizers increase myocardial contractility, but may worsen diastolic dysfunction. Levosimendan, through its unique troponin-C interaction, may preserve diastolic function. We investigated the effects of levosimendan (10(-7)-10(-5) M) on diastolic and systolic function in multicellular cardiac muscle preparations from end-stage failing human hearts (1 and 2.5 Hz, 37 degrees C, 1.25 mM [Ca(2+)], pH 7.4). Levosimendan improved systolic function: at 1 Hz, developed force (F(dev)) increased from 13.84+/-3.27 to 16.40+/-3.57 (10(-7) M, P<0.05), while diastolic force (F(dia)) decreased from 5.32+/-0.67 to 4.94+/-0.61 mN/mm(2) (P<0.05). Under control conditions, the increase in stimulation frequency from 1 to 2.5 Hz resulted in a decrease in F(dev) of -0.51+/-1.80 mN/mm(2) (negative force-frequency relationship). Levosimendan improved this relationship: at 10(-7) M, this change became positive (+1.81+/-2.06 mN/mm(2), P<0.05). Diastolic function was markedly improved in the presence of levosimendan; the increase in F(dia) of 1.56+/-0.42 mN/mm(2) (control) was attenuated to 0.70+/-0.19 mN/mm(2) (P<0.05). To allow for a more detailed analysis, preparations were sometimes divided into two groups, based on their force-frequency behavior. Twitch timing parameters were accelerated by levosimendan in preparations with a negative force-frequency relationship. Levosimendan improves both systolic and diastolic function in failing human myocardium. Effects are even more pronounced at higher heart rates and under prevailing diastolic dysfunction.
Assuntos
Cardiotônicos/farmacologia , Diástole/efeitos dos fármacos , Coração/efeitos dos fármacos , Hidrazonas/farmacologia , Piridazinas/farmacologia , Sístole/efeitos dos fármacos , Coração/fisiopatologia , Humanos , Isquemia Miocárdica , Miocárdio , SimendanaRESUMO
FK506 (tacrolimus) is a new immunosuppressant being used in cardiac allograft transplantation. While cyclosporine A has been shown to exert an acute negative inotropic effect on isolated heart muscle preparations, little is known of the inotropic influence of FK506. The Ca(2+) release channel of human skeletal muscle and cardiac muscle is associated with FK506 binding proteins (FKBP), FKBP12 and FKBP12.6, respectively. FKBPs can be dissociated by treatment with FK506. As a consequence of FK506 exposure, isolated skeletal muscle and cardiac muscle ryanodine receptors show altered gating characteristics. Therefore, we analyzed the direct inotropic effect of FK506 exposure to isolated, intact heart muscle preparations from the human and rabbits. Experiments were performed on isolated, electrically stimulated right atrial auricular muscle strips obtained from human myocardium during elective open heart surgery and on intact right ventricular trabeculae from rabbit hearts. The human preparations were exposed to concentrations of 8 x 10(-9), 8 x 10(-8) and 8 x 10(-6) M FK506 followed by a cumulative dose-response curve with isoprenaline as a non-selective beta-adrenoceptor agonist. Our data suggest that FK506 does not exert any positive or negative inotropic effect in either human or rabbit myocardium.
Assuntos
Agonistas Adrenérgicos beta/farmacologia , Imunossupressores/farmacologia , Isoproterenol/farmacologia , Contração Miocárdica/efeitos dos fármacos , Tacrolimo/farmacologia , Animais , Função Atrial , Ciclosporina/farmacologia , Relação Dose-Resposta a Droga , Átrios do Coração/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Humanos , Técnicas In Vitro , Coelhos , Função VentricularRESUMO
INTRODUCTION: Oxidative damage of the retinal pigment epithelium (RPE) may play a role in the development and progression of age-related macula degeneration (ARMD). Therapeutic reduction of oxidative stress failed or had only slight effects in ARMD patients. This study evaluates antiapoptotic properties of erythropoietin (epo) at the RPE as a novel approach to protect RPE cells against oxidative damage. MATERIALS AND METHODS: Cultured ARPE-19 cells were exposed to hydroxyl (OH) radicals generated from H(2)O(2) under catalysis of Fe(3+) (Fenton reaction) for 5 min. Apoptosis rate was determined by Annexin V labelling and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay. Epo was added in concentrations from 0 to 100 U/ml to the media 24 and 1 h before radical exposure as well as shortly after radical exposure. Expression of epo receptor was determined by western blotting. RESULTS: Hydroxyl radical exposure induced an increase of apoptosis rate from virtually 0 to 11.8+/-1.7%. Apoptosis was detectable up to 24 h after radical exposure and reached its maximum after 6 h. Epo reduced apoptosis rate by up to 88% even if applied after the radical exposure. Best protection was achieved at 5 U/ml epo. Western blot confirmed presence of epo receptor independent of a pre-incubation of the cells with epo. DISCUSSION: Epo exerts antiapoptotic effects on cultured RPE cells even if applied after the radical exposure. This might qualify epo as future candidate for therapy and prevention of dry ARMD.
Assuntos
Apoptose/efeitos dos fármacos , Eritropoetina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Western Blotting , Células Cultivadas , Humanos , Radical Hidroxila/farmacologia , Degeneração Macular/fisiopatologia , Estresse Oxidativo/fisiologia , Receptores da Eritropoetina/análise , Epitélio Pigmentado da Retina/citologiaRESUMO
Recently, Gao et al. published an experimental study based on the pathophysiology of diabetic macular edema in Nature Medicine (Nat Med. 2007 Feb;13(2):181-8). They found an increased amount of carbonic anhydrase in the vitreous, which causes a pH shift. This activates the kallikrein-kinin system and leads to increased retinal vascular permeability. In this comment the clinical implications of this article are discussed.
Assuntos
Anidrases Carbônicas/fisiologia , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/etiologia , Sistema Calicreína-Cinina/fisiologia , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Corpo Vítreo/enzimologia , Permeabilidade Capilar , Retinopatia Diabética/fisiopatologia , Humanos , Concentração de Íons de Hidrogênio , Edema Macular/fisiopatologia , Vasos Retinianos/fisiologiaRESUMO
BACKGROUND: In the pathophysiology of open-angle glaucoma altered perfusion of the optic nerve head is of importance. Up to now these disturbances were presumed to be the chief cause of glaucomatous damage in patients with normal tension glaucoma showing other vascular disturbances like migraine or tinnitus. PATIENTS AND METHODS: Peak systolic velocity (PSV) and end-diastolic velocity (EDV) were measured and the resistive index (RI) was calculated by colour Doppler imaging (CDI) in the ophthalmic artery (OA), central retinal artery (CRA) and in the short and long posterior ciliary arteries (SPCA, LPCA) in 18 patients with normal tension glaucoma (NTG), in 18 patients with high tension glaucoma (HTG) and in 18 normal control subjects. RESULTS: In an upright sitting position both glaucoma groups showed statistically significant decreases in PSV and EDV in CRA and SPCA compared to the control subjects. HTG when compared to NTG and normal subjects showed statistically significant decreases of EDV and statistically significant increases of RI in LPCA. In addition, compared to normal subjects, HTG patients showed statistically significant increases of RI in both OA and SPCA. DISCUSSION: Both glaucoma groups showed decreased blood flow velocities in the small retrobulbar vessels in an upright sitting position. Normal tension glaucoma patients with symptoms of vasospasms compared to patients with high tension glaucoma showed only small differences in ocular haemodynamics.
Assuntos
Velocidade do Fluxo Sanguíneo , Glaucoma/diagnóstico , Glaucoma/fisiopatologia , Transtornos de Enxaqueca/fisiopatologia , Disco Óptico/fisiopatologia , Doença de Raynaud/fisiopatologia , Zumbido/fisiopatologia , Feminino , Glaucoma/complicações , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/diagnóstico , Disco Óptico/irrigação sanguínea , Doença de Raynaud/complicações , Doença de Raynaud/diagnóstico , Valores de Referência , Zumbido/complicações , Zumbido/diagnósticoRESUMO
PURPOSE: Disturbed ocular haemodynamics are discussed to contribute to the pathogenesis of glaucoma. Up to now there is no method available allowing direct determination of blood flow, which is the most relevant dimension for studies on haemodynamics. In this study, volumetric colour Doppler imaging (vCDI) is evaluated systematically in glaucoma patients. METHODS: A Siemens Elegra ultrasound set-up with a linear 7.5 MHz probe was used for all CDI measurements. For vCDI, the cross-sectional area of a vessel and the flow velocity is determined. From both these parameters blood flow can be calculated. Ocular pulse amplitude (OPA) was assessed by the method of Langham using a pneumatic applanation tonometer. RESULTS: (1) Velocity measurements using CDI in the ophthalmic artery and central retinal artery were highly reproducible (n=20). In contrast, reproducibility of vCDI measurements was low (n=20). Reproducibility improved if five vCDI measures were averaged. (2) Results from two different CDI-operators did not differ regarding the velocity measurements, but there was a difference in vCDI measurements (n=20). (3) Results from vCDI did not correlate with measurements of OPA in 69 patients. (4) In 15 patients, vCDI failed to detect changes of ocular perfusion induced by the application of dorzolamide. CONCLUSION: vCDI is not applicable in ophthalmology at present.
Assuntos
Glaucoma/diagnóstico por imagem , Artéria Oftálmica/diagnóstico por imagem , Artéria Retiniana/diagnóstico por imagem , Adulto , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Glaucoma/tratamento farmacológico , Glaucoma/fisiopatologia , Humanos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Artéria Oftálmica/fisiopatologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Reprodutibilidade dos Testes , Artéria Retiniana/fisiopatologia , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Tiofenos/farmacologia , Tiofenos/uso terapêutico , Ultrassonografia Doppler em Cores/métodosRESUMO
BACKGROUND: It is taken for granted that glaucomatous damage is caused by changed haemodynamics of the retrobulbar vessel system besides other factors such as, for example, an elevated intraocular pressure. This was proven by various studies in which glaucoma patients were shown to have a changed retrobulbar blood flow velocity. In this study, the reliability of measurements of retrobulbar vessel perfusion by colour decoded Doppler imaging (CDI) was evaluated. PATIENTS AND METHODS: A total of 18 healthy volunteers and 15 patients with various glaucoma types were enrolled in this study. Using a CDI system, type Siemens Sonoline Elegra with a combined applicator (7.5L40), retrobulbar vessel perfusions of the ophthalmic artery, the short posterior ciliary arteries, and the long posterior ciliary arteries of each patient were measured six times. In each measurement, pulse amplitude, end-diastolic velocity, maximum systolic velocity, pulsatility index, and resistivity index of the vessels were determined. The reproducibility of measurements was evaluated by the calculation of the intraclass correlation coefficient (ICC) for each parameter. RESULTS: The ICCs for the ophthalmic artery varied from 0.89 to 0.98, for the short posterior ciliary artery from 0.75 to 0.91, and for the long posterior ciliary artery from 0.77 to 0.99 in both the groups. CONCLUSIONS: The ICCs of the repeated measurements reflect a good reproducibility for both the groups with assumed different retrobulbar perfusion. These findings are prerequisites for the use of CDI in clinical practice and research.
Assuntos
Artérias Ciliares/diagnóstico por imagem , Glaucoma/diagnóstico por imagem , Artéria Oftálmica/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo , Artérias Ciliares/fisiopatologia , Glaucoma/fisiopatologia , Humanos , Artéria Oftálmica/fisiopatologia , Fluxo Pulsátil , Fluxo Sanguíneo Regional , Reprodutibilidade dos Testes , Ultrassonografia Doppler em Cores/métodos , Resistência VascularRESUMO
Increased oxidative stress has been postulated as one of the main mechanisms underlying stunned myocardium, and may play an important role in and during development of heart failure. Pharmacological interventions may attenuate or prevent detrimental effects of oxygen free radicals on the myocardium. Nebivolol has been shown to attenuate contractile dysfunction in hydroxyl radical mediated injury, but the mechanism(s) remain unknown. It was investigated whether nebivolol could partly attenuate the contractile dysfunction through a direct effect on the myofilaments. In demembranized muscles from explanted human hearts, nebivolol induced a slight desensitization of the myofilaments to calcium. Therefore, during the calcium overload that occurs during reperfusion after an ischemic event, the contractile dysfunction is less severe in the presence of nebivolol. We conclude that the protection of nebivolol in hydroxyl radical induced contractile dysfunction is mediated in part through a direct effect on the myofilaments, in addition to the previously shown preservation of sarcoplasmic reticulum function.
Assuntos
Antagonistas de Receptores Adrenérgicos beta 1 , Antagonistas Adrenérgicos beta/farmacologia , Benzopiranos/farmacologia , Etanolaminas/farmacologia , Radical Hidroxila/metabolismo , Citoesqueleto de Actina/efeitos dos fármacos , Citoesqueleto de Actina/metabolismo , Animais , Cálcio/metabolismo , Cálcio/fisiologia , Feminino , Humanos , Peróxido de Hidrogênio/farmacologia , Técnicas In Vitro , Masculino , Contração Miocárdica/efeitos dos fármacos , Miocárdio/metabolismo , Miocárdio/ultraestrutura , Nebivolol , Oxidantes/farmacologia , Propranolol/farmacologia , CoelhosRESUMO
Beta-adrenoceptor antagonists (beta-blockers) are commonly used in clinical pharmacotherapy of cardiovascular diseases. Carvedilol and nebivolol possess beneficial effects on myocardial function in situations of oxidative stress associated with intracellular calcium overload. This preservation of contractile function might be due to direct scavenging capacities or to compensation of the intracellular calcium overload through direct impact on myofilament calcium sensitivity. Accordingly, we measured the relation between calcium and force in the absence and in the presence of 10(-6) M carvedilol, nebivolol, or propranolol in skinned right ventricular trabeculae of rabbit hearts. In rabbit myocardium, nebivolol (10(-6) M) altered the pCa50% by a rightward shift (less sensitive) from 5.72 +/- 0.05 to 5.57 +/- 0.05 (p < 0.05). Maximal force development was reduced by nebivolol. In contrast, the same concentration of propranolol or carvedilol did not influence calcium sensitivity and force development. In additional experiments, we repeated this protocol in trabeculae from human failing hearts. As in rabbit trabeculae, nebivolol shifted the pCa50% by 0.16 +/- 0.04 pCa units to the right (p < 0.05). Experiments with intact rabbit trabeculae confirmed depressed contractility: when all beta-adrenoceptors were blocked by 10(-6) M propranolol, subsequent addition of 10(-6) M nebivolol reduced developed force of these muscles significantly from 3.1 +/- 0.9 to 1.7 +/- 0.4 mN/mm2. We conclude that nebivolol desensitizes cardiac myofilaments slightly, whereas neither propranolol nor carvedilol had an effect.
Assuntos
Citoesqueleto de Actina/efeitos dos fármacos , Antagonistas Adrenérgicos beta/farmacologia , Benzopiranos/farmacologia , Carbazóis/farmacologia , Etanolaminas/farmacologia , Miocárdio , Propanolaminas/farmacologia , Citoesqueleto de Actina/fisiologia , Animais , Cloreto de Cálcio/farmacologia , Carvedilol , Feminino , Humanos , Contração Miocárdica/efeitos dos fármacos , Contração Miocárdica/fisiologia , Nebivolol , CoelhosRESUMO
BACKGROUND: Altered ocular perfusion plays a role in the pathophysiology of normal tension glaucoma. Prostaglandin-like substances are very effective in lowering intraocular pressure. Less data are available regarding the influence of these compounds on ocular perfusion. In the present study the effects of bimatoprost, which has recently been shown to increase the vascular tone of ciliary arteries in vitro, on the blood flow velocity are investigated. PATIENTS AND METHODS: n = 9 eyes from 9 normal tension glaucoma patients were subjected to color Doppler imaging (CDI) before and during a 3 - 5 week therapy with bimatoprost. RESULTS: Bimatoprost reduces intraocular pressure from 14.0 +/- 0.4 to 11.0 +/- 0.5 mmHg (n = 9; P < 0.001). Systolic as well as diastolic blood flow velocities, resistive index (RI) and pulsatility index (PI), measured by CDI, were unaltered in the presence of bimatoprost. DISCUSSION: Bimatoprost does not influence blood flow velocities in the retrobulbar vessels. The in vitro observation of increased vascular tone in the presence of bimatoprost seems not to be relevant for ocular hemodynamics.
Assuntos
Olho/irrigação sanguínea , Glaucoma de Ângulo Aberto/tratamento farmacológico , Hemodinâmica/efeitos dos fármacos , Lipídeos/administração & dosagem , Amidas , Bimatoprost , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Cloprostenol/análogos & derivados , Olho/diagnóstico por imagem , Humanos , Pressão Intraocular/efeitos dos fármacos , Lipídeos/efeitos adversos , Soluções Oftálmicas , Estudos Prospectivos , Ultrassonografia Doppler em CoresRESUMO
Catecholamines and elevated extracellular Ca(2+) concentration ([Ca(2+)](o)) augment contractile force by increased Ca(2+) influx and subsequent increased sarcoplasmic reticulum (SR) Ca(2+) release. We tested the hypothesis that pyruvate potentiates Ca(2+) release and inotropic response to isoproterenol and elevated [Ca(2+)](o), since this might be of potential importance in a clinical setting to circumvent deleterious effects on energy demand during application of catecholamines. Therefore, we investigated isometrically contracting myocardial preparations from rabbit hearts at 37 degrees C, pH 7.4, and a stimulation frequency of 1 Hz. At a [Ca(2+)](o) of 1.25 mM, pyruvate (10 mM) alone increased developed force (F(dev)) from 1.89 +/- 0.42 to 3.62 +/- 0.62 (SE) mN/mm(2) (n = 8, P < 0.05) and isoproterenol (10(-6) M) alone increased F(dev) from 2.06 +/- 0. 55 to 25.11 +/- 2.1 mN/mm(2) (P < 0.05), whereas the combination of isoproterenol and pyruvate increased F(dev) overproportionally from 1.89 +/- 0.42 to 33.31 +/- 3.18 mN/mm(2) (P < 0.05). In a separate series of experiments, we assessed SR Ca(2+) content by means of rapid cooling contractures and observed that, despite no further increase in F(dev) by increasing [Ca(2+)](o) from 8 to 16 mM, 10 mM pyruvate could still increase F(dev) from 26.4 +/- 6.8 to 29.7 +/- 7. 1 mN/mm(2) (P < 0.05, n = 9) as well as the Ca(2+) load of the SR. The results show that the positive inotropic effects of pyruvate potentiate the inotropic effects of isoproterenol or Ca(2+), because in the presence of pyruvate, Ca(2+) and isoproterenol induced larger increases in inotropy than can be calculated by mere addition of the individual effects.