Relationship between ocular perfusion pressure and retrobulbar blood flow in patients with glaucoma with progressive damage

PURPOSE: To evaluate the relationship between ocular perfusion pressure and color Doppler measurements in patients with glaucoma. MATERIALS AND METHODS: Twenty patients with primary open-angle glaucoma with visual field deterioration in spite of an intraocular pressure lowered below 21 mm Hg, 20 age-matched patients with glaucoma with stable visual fields, and 20 age-matched healthy controls were recruited. After a 20-minute rest in a supine position, intraocular pressure and color Doppler measurements parameters of the ophthalmic artery and the central retinal artery were obtained. Correlations between mean ocular perfusion pressure and color Doppler measurements parameters were determined. RESULTS: Patients with glaucoma showed a higher intraocular pressure (P <.0008) and a lower mean ocular perfusion pressure (P <.0045) compared with healthy subjects. Patients with deteriorating glaucoma showed a lower mean blood pressure (P =.033) and a lower end diastolic velocity in the central retinal artery (P =.0093) compared with normals. Mean ocular perfusion pressure correlated positively with end diastolic velocity in the ophthalmic artery (R = 0.66, P =.002) and central retinal artery (R = 0.74, P <.0001) and negatively with resistivity index in the ophthalmic artery (R = -0.70, P =.001) and central retinal artery (R = -0.62, P =.003) in patients with deteriorating glaucoma. Such correlations did not occur in patients with glaucoma with stable visual fields or in normal subjects. The correlations were statistically significantly different between the study groups (parallelism of regression lines in an analysis of covariance model) for end diastolic velocity (P =.001) and resistivity index (P =.0001) in the ophthalmic artery, as well as for end diastolic velocity (P =.0009) and resistivity index (P =. 001) in the central retinal artery. CONCLUSIONS: The present findings suggest that alterations in ocular blood flow regulation may contribute to the progression in glaucomatous damage.

Theoretical investigations of intercellular communication in the microcirculation: Conducted responses, myoendothelial projections and endothelium derived hyperpolarizing factor

The contractile state of microcirculatory vessels is a major determinant of the blood pressure of the whole systemic circulation. Continuous bi-directional communication exists between the endothelial cells (ECs) and smooth muscle cells (SMCs) that regulates calcium (Ca2+) dynamics in these cells. This study presents theoretical approaches to understand some of the important and currently unresolved microcirculatory phenomena. ^ Agonist induced events at local sites have been shown to spread long distances in the microcirculation. We have developed a multicellular computational model by integrating detailed single EC and SMC models with gap junction and nitric oxide (NO) coupling to understand the mechanisms behind this effect. Simulations suggest that spreading vasodilation mainly occurs through Ca 2+ independent passive conduction of hyperpolarization in RMAs. Model predicts a superior role for intercellular diffusion of inositol (1,4,5)-trisphosphate (IP3) than Ca2+ in modulating the spreading response. ^ Endothelial derived signals are initiated even during vasoconstriction of stimulated SMCs by the movement of Ca2+ and/or IP3 into the EC which provide hyperpolarizing feedback to SMCs to counter the ongoing constriction. Myoendothelial projections (MPs) present in the ECs have been recently proposed to play a role in myoendothelial feedback. We have developed two models using compartmental and 2D finite element methods to examine the role of these MPs by adding a sub compartment in the EC to simulate MP with localization of intermediate conductance calcium activated potassium channels (IKCa) and IP3 receptors (IP 3R). Both models predicted IP3 mediated high Ca2+ gradients in the MP after SMC stimulation with limited global spread. This Ca 2+ transient generated a hyperpolarizing feedback of ∼ 2–3mV. ^ Endothelium derived hyperpolarizing factor (EDHF) is the dominant form of endothelial control of SMC constriction in the microcirculation. A number of factors have been proposed for the role of EDHF but no single pathway is agreed upon. We have examined the potential of myoendothelial gap junctions (MEGJs) and potassium (K+) accumulation as EDHF using two models (compartmental and 2D finite element). An extra compartment is added in SMC to simulate micro domains (MD) which have NaKα2 isoform sodium potassium pumps. Simulations predict that MEGJ coupling is much stronger in producing EDHF than alone K+ accumulation. On the contrary, K+ accumulation can alter other important parameters (EC V m, IKCa current) and inhibit its own release as well as EDHF conduction via MEGJs. The models developed in this study are essential building blocks for future models and provide important insights to the current understanding of myoendothelial feedback and EDHF.^

Treinamento físico e fatores de risco cardiovascular em homens de meia-idade

Universidade Estadual de Campinas . Faculdade de Educação Física

Variabilidade da frequência cardíaca após treinamento concorrente : comparação entre homens e mulheres de meia-idade = Heart rate variability after concurrent training : comparison between middle-aged men and women

Universidade Estadual de Campinas . Faculdade de Educação Física

Avaliações autonômicas e cardiovasculares em pessoas com lesão da medula espinhal nas situações de repouso, em um teste de estresse mental e durante exercício físico

Universidade Estadual de Campinas . Faculdade de Educação Física

Comparação das respostas autonomicas e cardiorrespiratorias de homens e mulheres de meia-idade antes e apos treinamento fisico aerobio

Universidade Estadual de Campinas . Faculdade de Educação Física

Influencia do treinamento fisico aerobio sobre as respostas cardiovasculares e respiratorias em mulheres na menopausa com e sem terapia de reposição hormonal

Universidade Estadual de Campinas. Faculdade de Educação Física

Respostas cardiorrespiratorias ao exercicio fisico dinamico e função autonomica em primigestas

Universidade Estadual de Campinas . Faculdade de Educação Física

Effect of gender on training-induced vascular remodeling in SHR

There is accumulating evidence that physical inactivity, associated with the modern sedentary lifestyle, is a major determinant of hypertension. It represents the most important modifiable risk factor for cardiovascular diseases, which are the leading cause of morbidity and mortality for both men and women. In addition to involving sympathetic overactivity that alters hemodynamic parameters, hypertension is accompanied by several abnormalities in the skeletal muscle circulation including vessel rarefaction and increased arteriole wall-to-lumen ratio, which contribute to increased total peripheral resistance. Low-intensity aerobic training is a promising tool for the prevention, treatment and control of high blood pressure, but its efficacy may differ between men and women and between male and female animals. This review focuses on peripheral training-induced adaptations that contribute to a blood pressure-lowering effect, with special attention to differential responses in male and female spontaneously hypertensive rats (SHR). Heart, diaphragm and skeletal muscle arterioles (but not kidney arterioles) undergo eutrophic outward remodeling in trained male SHR, which contributed to a reduction of peripheral resistance and to a pressure fall. In contrast, trained female SHR showed no change in arteriole wall-to-lumen ratio and no pressure fall. On the other hand, training-induced adaptive changes in capillaries and venules (increased density) were similar in male and female SHR, supporting a similar hyperemic response to exercise.

A Comparison of Bimatoprost 0.03% Versus the Fixed-Combination of Latanotoprost 0.005% and Timolol 0.5% in Adult Patients With Elevated Intraocular Pressure: An Eight-Week, Randomized, Open-Label Trial

Introduction and Purpose: Bimatoprost and the fixed combination of latanoprost with timolol maleate are 2 medications widely used to treat glaucoma and ocular hypertension (OHT). The aim of the study is to compare the efficacy of these 2 drugs in reducing intraocular pressure (IOP) after 8 weeks of treatment in patients with primary open angle glaucoma (POAG) or OHT. Methods: In this randomized, open-label trial, 44 patients with POAG or OHT were allocated to receive either bimatoprost (1 drop QD) or latanoprost/timolol (1 drop QD). Primary outcome was the mean diurnal IOP measurement at the 8th week, calculated as the mean IOP measurements taken at 8:00 AM, 10: 00 AM, and 12: 00 PM Secondary outcomes included the baseline change in IOP measured 3 times a day, after the water-drinking test (performed after the last IOP measurement), and the assessment of side effects of each therapy. Results: The mean IOP levels of latanoprost/timolol (13.83, SD = 2.54) was significantly lower than of bimatoprost (16.16, SD = 3.28; P < 0.0001) at week 8. Also, the change in mean IOP values was significantly higher in the latanoprost/timolol group at 10:00 AM (P = 0.013) and 12:00 PM (P = 0.01), but not at 8: 00 AM (P = ns). During the water-drinking test, there was no signifi cant difference in IOP increase (absolute and percentage) between groups; however, there was a signifi cant decrease in mean heart rate in the latanoprost/timolol group. Finally, no signifi cant changes in blood pressure and lung spirometry were observed in either groups. Conclusions: The fixed combination of latanoprost/timolol was significantly superior to bimatoprost alone in reducing IOP in patients with POAG or OHT. Further studies with large sample sizes should be taken to support the superior efficacy of latanoprost/timolol, as well as to better assess its profile of side effects.

Endothelial Nitric Oxide Synthase Polymorphisms and Haplotypes in Amerindians

Interethnic disparities in the distribution of endothelial nitric oxide synthase (eNOS) polymorphisms may affect nitric oxide (NO)-mediated effects of and responses to drugs. While there are differences between black and white subjects there is no information regarding the distribution of eNOS gene alleles and haplotypes in Amerindians. We studied three clinically relevant eNOS polymorphisms (T(-786) C in the promoter, a variable number of tandem repeats in intron 4, and the Glu298Asp in exon 7) and eNOS haplotypes in 170 Amerindians from three tribes of the Brazilian Amazon. The results were compared with previous findings for black and white Brazilians. The Asp298, C(-786), and 4a alleles were much less common in Amerindians (5.0%, 3.2%, and 4.1%, respectively) than in blacks (15.1%, 19.5%, and 32.0%, respectively) or whites (32.8%, 41.9%, and 17.9%, respectively) (p<0.001). The haplotype including the most common alleles for each polymorphism was much more common in Amerindians (89%) than in blacks (45%) or whites (41%). Our findings are consistent with a lower genetic diversity in Amerindians compared with blacks and whites. These striking differences may be of major relevance for case-control association studies focusing on eNOS gene polymorphisms and may explain, at least in part, differences in the responses to cardiovascular drugs.

Change in central kinin B2 receptor density after exercise training in rats

Cardiovascular responses elicited by the stimulation of kinin B2 receptors in the IV cerebral ventricle paratrigeminal nucleus or in the thoracic spinal cord are similar to those observed during an exercise bout Considering that the kalikrein-kinin system (KKS) could act on the cardiovascular modulation during behavioral responses as physical exercise or stress this study evaluated the central B2 receptor densities of Wistar (W) and spontani ously hypertensive rats (SHR) after chronic moderate exercise Animals we re exercise-trained for ten weeks on a treadmill Afterwards systolic blood pressure decreased in both trained strains Animals were killed and the medulla and spinal cord extracted for B2 receptor autoradiography Trained animals were compared to their sedentary controls Sedentary groups showed specific binding sites for Hoe-140 (fmol/mg of tissue) in laminas 1 and 2 of the spinal cord nucleus of the solitary tract (NTS) area postrema (AP) spinal trigeminal tract (sp5) and paratrigeminal nucleus (Pa5) In trained W a significant increase (p<0 05) in specific binding was observed in the Pa5 (31 3%) and NTS (28 2%) Trained SHR showed a significant decrease in n ceptor density in lamina 2 (21 9%) of the thoracic spinal cord and an increase in specific binding in Pa5 (36 1%) We suggest that in the medulla chronic exercise could hyper stimulate the KKS enhancing their efficiency through the increase of B2 receptor density involving this receptor in central cardiovascular control during exercise or stress In the lamina 2 B2 receptor might be involved in the exercise-induced hypotension (C) 2010 Elsevier BV All rights reserved

Weight loss associated with exercise training restores ventilatory efficiency in obese children

The purpose of this study was to test the hypothesis that in obese children: 1) Ventilatory efficiency (VentE) is decreased during graded exercise; and 2) Weight loss through diet alone (D) improves VentE, and 3) diet associated with exercise training (DET) leads to greater improvement in VentE than by D. Thirty-eight obese children (10 +/- 0.2 years; BMI > 95(th) percentile) were randomly divided into two Study groups: D (n=17; BMI = 30 +/- 1 kg/m(2)) and DET (n = 21; 28 +/- 1 kg/m(2)). Ten lean children were included in a control group (10 +/- 0.3 years; 17 +/- 0.5 kg/m(2)). All children performed maximal treadmill testing with respiratory gas analysis (breath-by-breath) to determine the ventilatory anaerobic threshold (VAT) and peak oxygen consumption (VO(2) peak). VentE was determined by the VE/VCO(2) method at VAT. Obese children showed lower VO(2) peak and lower VentE than controls (p < 0.05). After interventions, all obese children reduced body weight (p < 0.05). D group did not improve in terms of VO(2) peak or VentE (p > 0.05). In contrast, the DET group showed increased VO(2) peak (p = 0.01) and improved VentE(Delta VE/VCO(2) = -6.1 +/- 0.9; p = 0.01). VentE is decreased in obese children, where weight loss by means of DET, but not D alone, improves VentE and cardiorespiratory fitness during graded exercise.

Baroreflex Sensitivity Impairment Is Associated With Cardiac Diastolic Dysfunction in Rats

Background: Studies have shown that the autonomic dysfunction accompanied by impaired baroreflex sensitivity was associated with higher mortality. However, the influence of decreased baroreflex sensitivity on cardiac function, especially in diastolic function, is not well understood. This study evaluated the morpho-functional changes associated with baroreflex impairment induced by chronic sinoaortic denervation (SAD). Methods and Results: Animals were divided into sinoaortic denervation (SAD) and control (C) groups. Baroreflex sensitivity was evaluated by tachycardic and bradycardic responses, induced by vasoactive drugs. Cardiac function was studied by echocardiography and by left ventricle (LV) catheterization. LV collagen content and the expression of regulatory proteins involved in intracellular Ca(2+) homeostasis were quantified. Results showed higher LV mass in SAD versus C animals. Furthermore, an increase in deceleration time of E-wave in the SAD versus the C group (2.14 +/- 0.07 ms vs 1.78 +/- 0.03 ms) was observed. LV end-diastolic pressure was increased and the minimum dP/dt was decreased in the SAD versus the C group (12 +/- 1.5 mm Hg vs 5.3 +/- 0.2 mm Hg and 7,422 +/- 201 vs 4,999 +/- 345 mm Hg/s, respectively). SERCA/NCX ratio was lower in SAD than in control rats. The same was verified in SERCA/PLB ratio. Conclusions: The results suggest that baroreflex dysfunction is associated with cardiac diastolic dysfunction independently of the presence of other risk factors. (J Cardiac Fail 2011;17:519-525)

Exercise training improves muscle vasodilatation in individuals with T786C polymorphism of endothelial nitric oxide synthase gene

Negrão M.V, Alves CR, Alves G.B, Pereira A.C, Dias R.G, Laterza M.C, Mota G.F, Oliveira E.M, Bassaneze V, Krieger J.E, Negrão C.E, Rondon M.U.P. Exercise training improves muscle vasodilatation in individuals with T786C polymorphism of endothelial nitric oxide synthase gene. Physiol Genomics 42A: 71-77, 2010. First published July 6, 2010; doi:10.1152/physiolgenomics.00145.2009.-Allele T at promoter region of the eNOS gene has been associated with an increase in coronary disease mortality, suggesting that this allele increases susceptibility for endothelial dysfunction. In contrast, exercise training improves endothelial function. Thus, we hypothesized that: 1) Muscle vasodilatation during exercise is attenuated in individuals homozygous for allele T, and 2) Exercise training improves muscle vasodilatation in response to exercise for TT genotype individuals. From 133 preselected healthy individuals genotyped for the T786C polymorphism, 72 participated in the study: TT (n = 37; age 27 +/- 1 yr) and CT + CC (n = 35; age 26 +/- 1 yr). Forearm blood flow (venous occlusion plethysmography) and blood pressure (oscillometric automatic cuff) were evaluated at rest and during 30% handgrip exercise. Exercise training consisted of three sessions per week for 18 wk, with intensity between anaerobic threshold and respiratory compensation point. Resting forearm vascular conductance (FVC, P = 0.17) and mean blood pressure (P = 0.70) were similar between groups. However, FVC responses during handgrip exercise were significantly lower in TT individuals compared with CT + CC individuals (0.39 +/- 0.12 vs. 1.08 +/- 0.27 units, P = 0.01). Exercise training significantly increased peak VO(2) in both groups, but resting FVC remained unchanged. This intervention significantly increased FVC response to handgrip exercise in TT individuals (P = 0.03), but not in CT + CC individuals (P = 0.49), leading to an equivalent FVC response between TT and CT + CC individuals (1.05 +/- 0.18 vs. 1.59 +/- 0.27 units, P = 0.27). In conclusion, exercise training improves muscle vasodilatation in response to exercise in TT genotype individuals, demonstrating that genetic variants influence the effects of interventions such as exercise training.