Microcirculatory changes as a hallmark of aging in the heart and kidney / Cambios microcirculatorios como sello distintivo del envejecimiento en el corazón y riñón

SUMMARY: Changes in the microcirculation of multiple tissues and organs have been implicated as a possible mechanism in physiological aging. In particular, vascular endothelial growth factor is a secretory protein responsible for regulating angiogenesis via altering endothelial proliferation, survival, migration, extracellular matrix degradation and cell permeability. The aim of the present study was to evaluate the role of vascular endothelial growth factor in the progression of morphological alterations caused by physiological aging in the heart and kidney and to examine its relation to changes in capillary density. We used two age groups of healthy Wistar rats - 6- and 12-month- old. The expression of vascular endothelial growth factor was examined through immunohistochemistry and immunofluorescence and assessed semi-quantitatively. Changes in capillary density were evaluated statistically and correlated with the expression of vascular endothelial growth factor. We reported stronger immunoreactivity for vascular endothelial growth factor in the left compared to the right ventricle and also observed an increase in its expression in both ventricles in older animals. Contrasting results were reported for the renal cortex and medulla. Capillary density decreased statistically in all examined structures as aging progressed. The studied correlations were statistically significant in the two ventricles in 12-month-old animals and in the renal cortex of both age groups. Our results shed light on some changes in the microcirculation that take place as aging advances and likely contribute to impairment in the function of the examined organs.

Los cambios en la microcirculación de múltiples tejidos y órganos se han implicado como un posible mecanismo en el envejecimiento fisiológico. En particular, el factor de crecimiento endotelial vascular es una proteína secretora responsable de regular la angiogénesis mediante la alteración de la proliferación endotelial, la supervivencia, la migración, la degradación de la matriz extracelular y la permeabilidad celular. El objetivo del presente estudio fue evaluar el papel del factor de crecimiento del endotelio vascular en la progresión de las alteraciones morfológicas causadas por el envejecimiento fisiológico en el corazón y riñón y examinar su relación con los cambios en la densidad capilar. Utilizamos dos grupos de ratas Wistar sanas: 6 y 12 meses de edad. La expresión del factor de crecimiento del endotelio vascular se examinó mediante inmunohistoquímica e inmunofluorescencia y se evaluó semicuantitativamente. Los cambios en la densidad capilar se evaluaron estadísticamente y se correlacionaron con la expresión del factor de crecimiento del endotelio vascular. Informamos una inmunorreactividad más fuerte para el factor de crecimiento endotelial vascular en el ventrículo izquierdo en comparación con el derecho y también observamos un aumento en su expresión en ambos ventrículos en animales mayores. Se informaron resultados contrastantes para la corteza renal y la médula. La densidad capilar disminuyó estadísticamente en todas las estructuras examinadas a medida que avanzaba el envejecimiento. Las correlaciones estudiadas fueron estadísticamente significativas en los dos ventrículos en animales de 12 meses y en la corteza renal de ambos grupos de edad. Nuestros resultados arrojan luz sobre algunos cambios en la microcirculación que tienen lugar a medida que avanza el envejecimiento y probablemente contribuyan a un deterioro en la función de los órganos examinados.

Comparison of radial peripapillary capillary density results of individuals with and without Helicobacter pylori infection / Comparação dos resultados da densidade capilar peripapilar radial de indivíduos com e sem infecção por Helicobacter pylori

ABSTRACT Purpose: To evaluate the radial peripapillary capillary density using optical coherence tomography angiography in patients with and without Helicobacter pylori infection. Methods: This prospective, cross-sectional study comprised 52 patients (52 eyes: Group 1) and 38 patients (38 eyes: Group 2) with and without H. pylori infections, respectively. The radial peripapillary capillary density and retinal nerve fiber layer thickness in 4 equal quadrants and 2 equal hemispheres in the peripapillary region were calculated using optical coherence tomography angiography. The optic nerve head parameters of the patients were also assessed. Results: The groups were similar in terms of age, gender, and the optic nerve head parameters. The radial peripapillary capillary densities in the superior hemisphere and quadrant were significantly lower in Group 1 than in Group 2 (p=0.039 and p=0.028, respectively) and were positively correlated with the superior hemisphere's retinal nerve fiber layer thickness (p<0.001 and p<0.001, respectively). Similarly, the radial peripapillary capillary densities in the inferior hemisphere and quadrant were also significantly lower in Group 1 compared to Group 2 (p=0.03 and p=0.017, respectively) and were positively correlated with the inferior hemisphere's retinal nerve fiber layer thickness (p<0.001 and p<0.001, respectively). The retinal nerve fiber layer thickness in the nasal and temporal quadrants were significantly decreased in Group 1 when compared to Group 2 (p=0.013 and p=0.022) and were positively correlated with the corresponding radial peripapillary capillary densities of the 2 quadrants (p=0.002 and p=0.022). Conclusion: The decreased radial peripapillary capillary density in the H. pylori-positive patients suggests that H. pylori may play a role in the etiopathogenesis of glaucoma.

RESUMO Objetivos: Avaliar a densidade capilar peripapilar radial de pacientes com e sem infecção por Helicobacter pylori (H. pylori) por meio de angiotomografia de coerência óptica. Métodos: Cinquenta e dois olhos de 52 pacientes com infecção por H. pylori (Grupo 1) e 38 olhos de 38 pacientes sem infecções por H. pylori (Grupo 2) foram incluídos neste estudo prospectivo e transversal. A densidade capilar peripapilar radial (%) e a espessura da camada de fibra nervosa retiniana (μm) em 4 setores iguais e 2 hemisférios iguais foram calculados automaticamente na região peripapilar por angiotomografia de coerência óptica. Os parâmetros da cabeça do nervo óptico dos pacientes também foram avaliados. Resultados: Os grupos foram semelhantes em relação aos parâmetros: idade, sexo e cabeça do nervo óptico. As densidades capilares peripapilares radiais no hemisfério superior, hemisfério inferior, quadrante superior e quadrante inferior foram significativamente menores no Grupo 1 do que no Grupo 2 (p=0,039, p=0,03, p=0,028 e p=0,017 respectivamente). As densidades capilares peripapilares radiais, tanto no hemisfério superior quanto no quadrante superior, foram correlacionadas positivamente com a espessura da camada de fibra nervosa da retina do hemisfério superior (p<0,001 e p<0,001). As densidades capilares peripapilares radiais no hemisfério inferior e no quadrante inferior foram positivamente correlacionadas com a espessura da camada do nervo retiniano do hemisfério inferior (p<0,001 e p<0,001). A espessura da camada da fibra nervosa retiniana nos quadrantes nasal e temporal diminuiu significativamente no Grupo 1 quando comparado ao Grupo 2 (p=0,013 e p=0,022), e esses valores foram positivamente correlacionados com as densidades capilares peripapilares radiais correspondentes nos quadrantes nasal e temporal (p=0,002 e p=0,022). Conclusão: A diminuição das densidades capilares peripapilares radiais nos olhos de indivíduos positivos para H. pylori sugere que H. pylori pode desempenhar um papel na etiopatogenia do glaucoma.

Comparison of macular vascular density and retinal thickness in children with different degrees of myopia / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To observe and compare the changes of macular vascular density and retinal thickness in children and adolescents with different degrees using optical coherence tomography angiography(OCTA), then analyze their correlation.<p>METHODS: Our prospective cross-sectional study included 230 eyes of 115 children and adolescents aged 6-18a. According to spherical equivalent power(SE), they were divided into four groups: emmetropia group(32 eyes of 16 cases), mild myopia group(94 eyes of 47 cases), moderate myopia group(68 eyes of 34 cases), and high myopia group(36 eyes of 18 cases). Using RTVue XR scans of the 6mm×6mm region of the macula, the system automatically divided it into three rings: 1mm(fovea)ring, 1mm-3mm(parafovea)ring, and 3mm-6mm(perifovea)ring. And each ring was further divided into four quadrants: temporal(T), superior(S), nasal(N), and inferior(I). Quantitatively analysis was performed for the superficial and deep capillary densities and retinal thickness of each sector.<p>RESULTS: The superficial capillary density in the macula was in turn significantly decreased as in emmetropia(44.4±3.5)%, mild myopia(44.8±3.8)%, moderate myopia(44.3±3.8)%, and high myopia(42.6±4.5)% groups(<i>F</i>=2.963,<i>P</i>=0.033). The superficial capillary density of parafovea's temporal side were(46.1±3.5)%,(46.8±5.1)%,(46.2±4.3)%, and(43.8±5.5)% in the four groups, respectively(<i>F</i>=3.436, <i>P</i>=0.018). Similarly, the deep capillary density of the four groups was(49.9±4.1)%,(48.4±4.7)%,(47.9±5.5)%, and(45.3±4.7)%, respectively(<i>F</i>=4.806, <i>P</i>=0.003). The deep capillary density of the perifovea was(49±4.4)%,(47.2±5.2)%,(46.6±6)%, and(43.6±5.1)% in the 4 groups, respectively(<i>F</i>=5.495, <i>P</i>=0.001). The retinal thickness of the four groups was 293.9±12.9, 295.5±13.0, 290.9±12.0, and 284.5±10.7 μm(<i>F</i>=6.606, <i>P</i><0.001). The superficial capillary densities of parafoveal's temporal and nasal sides were positively correlated with SE(<i>r</i>=0.221, 0.219, <i>P</i>=0.001, 0.001). The deep capillary density of perifovea's temporal, superior, nasal and inferior side were positively correlated with SE(<i>r</i>=0.172, 0.200, 0.250, 0.296, <i>P</i>=0.011, 0.003, <0.001, <0.001). The central retinal thickness except the fovea were positively correlated with SE(<i>P</i><0.05).<p>CONCLUSION: With the increase of myopia degree of children and adolescents, the superficial capillaries density in the macula decreases, especially in the parafovea's temporal side; as well as the deep capillaries density, especially decreases in the perifovea. The central retinal thickness decreases in both parafovea and perifovea. With the myopia degree of children and adolescents increases, the structure and capillary circulation of the macula will be influenced, especially in the high myopia group.

Acupoint injection of BMSCs combined with Chinese herbs for capillary density in ischemic hind limb of diabetes mellitus rats / 中国针灸

OBJECTIVE@#To observe the effect of acupoint injection of bone mesenchymal stem cells (BMSCs) combined with Chinese herbs of benefiting for activating blood circulation for capillary density and arterioles density in skeletal muscle in ischemic hind limb of diabetes mellitus (DM) rats.@*METHODS@#A total of 80 rats were randomized into a normal sham operation group (10 rats) and a model group (70 rats). Disposable intraperitoneal injection of streptozotocin (STZ, 50.0 mg/kg) was used to establish DM model, and the rats in the model group were randomized into 7 subgroups, 10 rats in each one. The subgroups were the DM sham operation group, DM ischemic group, Chinese herb group (intragastric herbs of benefiting for activating blood circulation), local injection group (BMSCs local injection), local injection + Chinese herb group (BMSCs local injection combined with intragastric herbs of benefiting for activating blood circulation), acupoint injection group (BMSCs acupoint injection), acupoint injection + Chinese herb group (BMSCs acupoint injection combined with intragastric herbs of benefiting for activating blood circulation). The local injection was phosphate buffer (PBS) injection at the equidistant 5 points along the line between the ischemic tissue and the normal tissue a time. The acupoints were "Sanyinjiao" (SP 6), "Zhaohai" (KI 6), "Huantiao" (GB 30), "Housanli" (ST 36) and "Yanglingquan" (GB 34). 100 μL BMSCs with 1×10/mL was totally injected at the above acupoints for one rat, 20 μL an acupoint. 1.5 kg/L Chinese herbs were applied by intragastric administration, including 120 g Radix Astragali, 120 g Codonopsis, 48 g Radix Glycyrrhiza, 120 g Angelica sinensis, 120 g Blood Rattan, 48 g Achyranthes bidentata. Intragastric distilled water was used in the other non-Chinese herb groups. The expressions of α-smooth muscle actin (α-actin), latelet endothelial cell adhesion molecule (CD31) and von willebrand factor (vWF) in the skeletal muscle were detected with immunohistochemical SP two-step method.@*RESULTS@#Twenty-one days after intervention, the expressions of α-actin and CD31 on the operation hind limb were higher than those on the healthy hind limb in all the groups, except the Chinese herb group (<0.05<0.01). The vWF expressions on the operation side were lower than those on the healthy side in the Chinese herb group, the local injection group, the local injection + Chinese herb group and the acupoint injection + Chinese herb group (<0.05, <0.01). The α-actin expression on the operation side in the acupoint injection + Chinese herb group was higher than those in the normal sham operation group, DM sham operation group, the DM ischemic group and the local injection group (<0.05, <0.01). The CD31 expressions in the acupoint injection group, the acupoint injection + Chinese herb group, local injection + Chinese herb group were higher than those in the normal sham operation group, DM sham operation group and DM ischemic group (<0.05, <0.01). The CD31 expression in the acupoint injection + Chinese herb group was higher than those in the Chinese herb group and the local injection group (both <0.05). The vWF expressions in the local injection + Chinese herb group, the acupoint injection group and the acupoint injection + Chinese herb group lower than those in the DM sham operation group and the DM ischemic group (<0.05, <0.01).@*CONCLUSION@#schemia increases the expressions of the vascular density related factors of α-actin and CD31. It is more obvious for the increasing expressions of α-actin and CD31, and decreasing expression of vWF with the interventions of simple BMSCs injection and simple Chinese herbs of benefiting for activating blood circulation, especially with the combination of the above tow methods. It is indicated that acupoint injection of BMSCs combined with Chinese herbs of benefiting for activating blood circulation can improve the angiogenesis of ischemic tissue.

Effects of Treadmill Running on Capillary Density and Apelin Expression in Soleus Muscle of High-fat Diet Rats / 中国运动医学杂志

Objective To observe the alteration of capillary density and apelin/APJ expression in soleus muscles of high-fat diet rats.Methods Male 5-week-old Sprague-Dawley rats were randomly divided into a control group and a high-fat diet group.After 12 weeks of high-fat diet,16 rats were se lected and randomly divided into a sedentary group and a treadmill running group.The exercise rats underwent 60-minute treadmill running at 26 m/min 5 days a week for 10 weeks.The body weight,body fat and blood lipid level were measured for all rats.The protein expression of Soleus CD31 and apelin was determined using immunohistochemical staining,soleus apelin content was determined using the radioimmunoassay,and the mRNA expression of apelin/APJ was detected using real-time PCR.Results Compared with the control group,significant increase was observed in the body weight,body fat and the level of total triglyceride,total cholesterol and low density lipoprotein cholesterin,but significant decrease was found in the high density lipoprotein cholesterin in the high-fat diet group.There were no significant differences in the capillary density and mRNA levels of apelin/APJ between the two groups.Compared with the sedentary high-fat diet group,significant improvement was observed in the body weight and blood lipid level of the treadmill running group.Moreover,significant increase was also observed in the capillary density,the expression of apelin/APJ mRNA,as well as that of apelin protein in the treadmill running group (P＜0.05).Conclusion The treadmill running can significantly increase capillary density of obese rats,as it may activate the expression of Apelin/APJ.

Estrogen deficiency in ovariectomized rats: can resistance training re-establish angiogenesis in visceral adipose tissue?

OBJECTIVE: The purpose of this study was to investigate the effects of resistance training on angiogenesis markers of visceral adipose tissue in ovariectomized rats. METHOD: Adult Sprague-Dawley female rats were divided into four groups (n=6 per group): sham-sedentary, ovariectomized sedentary, sham-resistance training and ovariectomized resistance training. The rats were allowed to climb a 1.1-m vertical ladder with weights attached to their tails and the weights were progressively increased. Sessions were performed three times per week for 10 weeks. Visceral adipose tissue angiogenesis and morphology were analyzed by histology. VEGF-A mRNA and protein levels were analyzed by real-time PCR and ELISA, respectively. RESULTS: Ovariectomy resulted in higher body mass (p=0.0003), adipocyte hypertrophy (p=0.0003), decreased VEGF-A mRNA (p=0.0004) and protein levels (p=0.0009), and decreased micro-vascular density (p=0.0181) in the visceral adipose tissue of the rats. Resistance training for 10 weeks was not able to attenuate the reduced angiogenesis in the visceral adipose tissue of the ovariectomized rats. CONCLUSION: Our findings indicate that the resistance training program used in this study could not ameliorate low angiogenesis in the visceral adipose tissue of ovariectomized rats.

Effect of Electroacupuncture at Hegu (LI04) on Capillary Density and Expression of CD34 after Focal Cerebral Ischemia/Reperfusion in Rats / 中国康复理论与实践

@# Objective To observe the effect of electroacupuncture at Hegu (LI04) on capillary density and expression of CD34 after focal cerebral ischemia/reperfusion in rats. Methods 90 rats were randomly divided into normal group (n=6), model group (n=42) and electroacupuncture group (n=42). A rat model of focal cerebral ischemia/reperfusion was made by filament occlusion in the model group and the electroacupuncture group. And the electroacupuncture group received electroacupuncture. They were observed 2 h, 12 h, 24 h, 3 d, 7 d, 14 d, 21 d after reperfusion 1 h followed ischemia. HE staining was used to observe and calculate the infarct volume and capillary density, and immunohistology was used to detect the expression of CD34 after neurologic symptoms rating. Results Compared with the model group, the neurologic symptoms score significantly decreased 2 h after reperfusion in the electroacupuncture group (P<0.01), and still decreased 21 d after reperfusion (P<0.05). The infarct volume significantly was smaller in the electroacupuncture group than in the model group (P<0.01). The capillary density was higher 2 h, 24 h, 3 d, 7 d, 14 d after reperfusion in the electroacupuncture group than in the model group (P<0.05). Compared with the model group, the expression of CD34 significantly increased 3 d after reperfusion in the electroacupuncture group (P<0.01),and it reached a peak at 7 d after reperfusion (P<0.01), and still higher at 14 d. Conclusion Electroacupuncture can promote the expression of CD34 and the capillary density, and stimulate the angiogenesis after focal ischemia/reperfusion.

Effect of Electroacupuncture at Hegu (LI04) on Capillary Density and Expression of CD34 after Focal Cerebral Ischemia/Reperfu-sion in Rats / 中国康复理论与实践

Objective To observe the effect of electroacupuncture at Hegu (LI04) on capillary density and expression of CD34 after focal cerebral ischemia/reperfusion in rats. Methods 90 rats were randomly divided into normal group (n=6), model group (n=42) and electroacu-puncture group (n=42). A rat model of focal cerebral ischemia/reperfusion was made by filament occlusion in the model group and the elec-troacupuncture group. And the electroacupuncture group received electroacupuncture. They were observed 2 h, 12 h, 24 h, 3 d, 7 d, 14 d, 21 d after reperfusion 1 h followed ischemia. HE staining was used to observe and calculate the infarct volume and capillary density, and immu-nohistology was used to detect the expression of CD34 after neurologic symptoms rating. Results Compared with the model group, the neuro-logic symptoms score significantly decreased 2 h after reperfusion in the electroacupuncture group (P<0.01), and still decreased 21 d after re-perfusion (P<0.05). The infarct volume significantly was smaller in the electroacupuncture group than in the model group (P<0.01). The cap-illary density was higher 2 h, 24 h, 3 d, 7 d, 14 d after reperfusion in the electroacupuncture group than in the model group (P<0.05). Com-pared with the model group, the expression of CD34 significantly increased 3 d after reperfusion in the electroacupuncture group (P<0.01), and it reached a peak at 7 d after reperfusion (P<0.01), and still higher at 14 d. Conclusion Electroacupuncture can promote the expression of CD34 and the capillary density, and stimulate the angiogenesis after focal ischemia/reperfusion.

Muscle fiber type composition, fiber diameter, capillary density in temporalis and masseter muscles and correlation with bite force / Tipos de fibras musculares, diámetro de fibras y densidad capilar en los músculos masetero y temporal y su correlación con la fuerza de mordida

The jaw muscles are essential components in the stomatognatic system. Their complex architecture allows them to execute several motor tasks. One of the structural peculiarities is the presence of hybrid and neonatal fibers.We studied the differences of the fiber-type in masseter and temporalis muscles along the first to nineth decades in both genders. Seventy-four (74) samples were analyzed by immunohistochemistry. Slow and fast muscle fibers distribution was similar in both muscles in both genders. Hybrid fiber was observed in all decades, and its frequency decreased significantly (p<0.001) with aging in masseter. Neonatal myosin expression was observed in all decades, its expression was more frequent in masseter (p=0.01), and males in temporalis (p=0.025). Decrease of the cross sectional area of fast and slow fibers, and decrease of capillary density were detected with aging. These morpho-immunohistochemical alterations on masseter and temporalis muscles correlated to the decrease in bite force with aging.

Los músculos cráneomandibulares son componentes esenciales en el sistema estomatognático. Su arquitectura compleja les permite ejecutar variadas tareas motoras. Una de sus características estructurales es la presencia de fibras musculares híbridas y neonatales. Se estudiaron las diferencias del tipo de fibra en los músculos masetero y temporal en la primera a novena décadas dela vida en ambos sexos. Setenta y cuatro (74) muestras se analizaron por inmunohistoquímica. La distribución de lãs fibras musculares lentas y rápidas fue similar en ambos músculos en ambos sexos. Fibras musculares híbridas fueron observadas en todas las décadas, pero su frecuencia disminuyó significativamente (p <0,001) con el envejecimiento en el masétero. La expresión de miosina neonatal se observo em todas los grupos analizados, aunque su expresión era más frecuente en los músculos maseteros (p = 0,01) y en varones en el temporal (p = 0,025). Se observo una disminución del área de la sección transversal de las fibras rápidas y lentas, y disminución de la densidad capilar al aumentar La edad. Estas alteraciones morfológicas en los músculos masetero y temporal se correlacionan con la disminución de la fuerza asociada al envejecimiento.

The Effect of Transcutaneous Carbon Dioxide (CO₂) Application after Endurance Exercise in Rats / The Japanese Journal of Rehabilitation Medicine

Objective : In Europe, carbon dioxide therapy has been used for treating cardiac disease and skin problems for a long time. Previously, we demonstrated that transcutaneous carbon dioxide (CO₂) application facilitated dioxygen (O₂) dissociation from hemoglobin (Hb) in the human body. Additionally, we proved that transcutaneous CO₂ application to the lower limbs of rats increased the expression of peroxisome proliferator-activated receptor (PPAR) gamma coactivator-1α (PGC-1α), vascular endothelial growth factor (VEGF) and silent mating type information regulation 2 homologs 1 (SIRT1). It also increased the number of mitochondria, and changed IIB fiber to IIA fiber in similar manner to the change that occurs after exercise. The transcutaneous CO₂ application caused a similar effect to that of exercise training in skeletal muscle and indicated the possibility of improved endurance strength. However, the effect of transcutaneous CO₂ application on endurance exercise and the recovery of muscle fatigue has not been studied. Methods : In this study, we investigated the performance of endurance exercise in rats with/without transcutaneous CO₂ application and analyzed the muscle fiber changes, capillary density and mitochondrial DNA number of the skeletal muscles after training, using activity wheels. Results： Training with CO₂ application resulted in a higher percentage of TA muscle transformed to IIA and/or IID than training alone, suggesting that transcutaneous CO₂ application may increase the production of ATP, mitochondria number, and capillary density. Therefore, transcutaneous CO₂ application might lead to muscle damage recovery. Conclusion : We suggest that transcutaneous CO₂ application has a therapeutic potential for recovery of damaged muscle after excessive exercise and rehabilitation.

Change of Capillary Pericapillary Cells in Rats with Myocardial Infarction and Effect of Supplementing Qi and Activating Blood Circulation Herbs / 中国中医药信息杂志

Objective To observe the change of capillary pericapillary cells in rats with myocardial infarction and the influence of supplementing qi and activating blood circulation herbs, and explore its mechanism of improving myocardial perfusion. Methods The rat model was established by ligaturing the left anterior descending coronary artery. On the base of ECG evaluation, successfully modeled rats were randomly divided into the model group, group treated with supplementing qi and activating blood circulation Chinese medicine (activating blood and supplementing qi group), group treated with Perindopril (Perindopril group), group treated with Tongxinluo Capsules (Tongxinluo group). The sham-operation group was taken as the control. There were totally 5 groups. The model group and the sham-operation group were treated with normal saline. The changes of myocardial capillary density (MCD) and number of pericapillary cells on the 7th, 28th day after medicinal administration were observed. Results On the 7th and 28th day, the MCD decreased significantly and the number of capillary pericapillary cells increased significantly in the model group compared with the sham-operation group (P<0.01). The MCD increased significantly in the activating blood and supplementing qi group, Perindopril group and Tongxinluo group compared with the model group (P<0.01). The number of pericapillary cells decreased significantly in the activating blood and supplementing qi group, Perindopril group and Tongxinluo group compared with the model group (P<0.01). Conclusion The supplementing qi and activating blood circulation herbs can improve regional myocardial blood supply by decreasing the number of pericytes and promoting regeneration of capillary.

Efeitos macrovasculares, microvasculares e interação leucócito-endotélio, na endotoxemia experimental após o uso de Dobutamina com e sem ressuscitação volêmica / Macrovascular and microvascular effects and leukocyte-endothelial interaction in experimental endotoxemia after use of dobutamine with and without volume ressuscitation

Na sepse, o mecanismo desencadeador de morte é a disfunção múltipla de órgãos e sistemas. Com isso a microcirculação é considerada o motor na patogênese da sepse. A perfusão microcirculatória representa um dos principais objetivos para melhorar as taxas de sobrevida. Uma vez reconhecida a síndrome séptica, o protocolo clínico estabelece o uso de fluidoterapia com salina, de forma vigorosa na primeira hora e seguida de suporte inotrópico com Dobutamina. A partir daí foi levantada a hipótese das drogas β-agonistas serem relevantes na recuperação da microcirculação, antes mesmo de seu conhecido papel na recuperação do choque cardiogênico. Assim, estudar o papel da Dobutamina, um β-agonista, na resposta adrenérgica em situação de sepse se faz necessário e urgente e o entendimento de sua ação, associada à reposição volêmica, foi objeto deste estudo. Foram usados no presente estudo, 78 hamsters, induzida a endotoxemia com LPS (2mg/kg/de massa de peso corporal) e divididos em 9 grupos: controle (n=10), endotóxico(n=10), endotóxico tratados com Dobutamina na dose de 5 e 15 μg /kg/min (n=10), Isoproterenol(n=10), ressuscitação volêmica (n=10) e ressuscitação volêmica associada à Dobutamina 5 (n=10) e 15 μg/kg/min (n=4) e Isoproterenol (n=4). Foram comparados os resultados de recuperação da densidade capilar funcional ao longo do tempo entre os grupos, e obteve-se resultado estatisticamente significativo no grupo em que se usa Dobutamina de 5μg/kg/min associada à ressuscitação volêmica p< 0,05. Em conclusão este estudo mostra que o papel da ressuscitação volêmica é crucial na resposta da microcirculação para melhorar a densidade capilar funcional, que a velocidade da hemácia capilar tem relação direta com a melhora na perfusão tecidual e que a associação de recuperação volêmica com solução salina e Dobutamina na dose de 5 μg /kg /min melhora significativamente sua resposta e melhora a perfusão.

uring sepsis the mechanism responsible for death is multiple dysfunctions of organs and systems and therefore the microcirculation is considered the motor in the pathogenesis of sepsis and microcirculatory perfusion represents one of the main objectives to improve survival rate. Once one recognizes the septic syndrome, the clinical protocol establishes the use of fluid therapy with physiological saline, in a vigorous way, in the first hour followed by inotropic support with dobutamine. With these facts in mind, our hypothesis is that β-agonist drugs are relevant for microcirculatory recuperation, even before their role was known in the recuperation of cardiogenic shock. In this way, to study the role of dobutamine, a β-agonist, in the adrenergic response in sepsis is needed and urgent. The understanding of its action associated to volume resuscitation was the aim of our study. Seventy-eight male hamsters were used in our study, endotoxemia being induced with LPS (2 mg/kg body weight), divided in 9 groups: control (n=10), endotoxic (n=10), endotoxic treated with dobutamine in the concentrations of 5 and 15 μg/kg/min (n=10, each), isoproterenol (n=10), volume resuscitation associated to dobutamine 5 μg/kg/min (n=10), 15 μg/kg/min (n=4), isoproterenol (n=4) or not (n=10). The microcirculation was observed in the dorsal window chamber and the results compared the recuperation of function capillary density with time and the group treated with dobutamine 5 μg/kg/min associated to volume resuscitation showed a statistically significant improvement (p<0.05) of it. In conclusion, this study has shown that volume resuscitation plays a crucial role in the microcirculatory response in terms of improvement of functional capillary density, the velocity of red blood cells in the capillary has a direct relationship with the improvement of tissue perfusion and the association of volume resuscitation with physiological saline and dobutamine 5 μg/kg/min elicits ...

Effects of diabetes on myocardial capillary density and serum angiogenesis biomarkers in male rats

INTRODUCTION: Cardiovascular disease is one of the main causes of mortality and morbidity in diabetic patients. This study evaluated the effects of diabetes on myocardial capillary density and several serum angiogenic factors including nitric oxide, vascular endothelial growth factor, and soluble vascular endothelial growth factor receptors. METHODS: Twelve male rats were divided into two groups: control and diabetic (n = 6 each). Diabetes was induced with a single dose of streptozotocin (50 mg/kg). After 21 days, capillary density in the myocardial tissue was evaluated using immunohistochemical staining and is reported as capillaries per mm². Blood samples were collected before and after the induction of diabetes. RESULTS: In the diabetic group, serum nitric oxide and soluble vascular endothelial growth factor receptor 2 concentrations were lower than the levels in the control group, while the level of soluble vascular endothelial growth factor receptor 1 was significantly higher. There was no significant change in the serum vascular endothelial growth factor concentration between the diabetic and control groups; however, the ratio of vascular endothelial growth factor to vascular endothelial growth factor receptor 1 was significantly lower in the diabetic animals. The myocardial capillary density was also lower in the diabetic group compared with the control group (1549 ± 161 vs. 2156 ± 202/mm², respectively). CONCLUSION: Reduced serum nitric oxide and vascular endothelial growth factor receptor 2 levels, increased serum vascular endothelial growth factor receptor 1 levels and a lower vascular endothelial growth factor to vascular endothelial growth factor receptor 1 ratio may be responsible for the decreased myocardial capillary density in diabetic rats.

Time course of training-induced microcirculatory changes and of vegf expression in skeletal muscles of spontaneously hypertensive female rats

Exercise-induced vessel changes modulate arterial pressure (AP) in male spontaneously hypertensive rats (SHR). Vascular endothelial growth factor (VEGF) is important for angiogenesis of skeletal muscle. The present study evaluated the time course of VEGF and angiogenesis after short- and long-term exercise training of female SHR and Wistar Kyoto (WKY) rats, 8-9 weeks (200-250 g). Rats were allocated to daily training or remained sedentary for 3 days (N = 23) or 13 weeks (N = 23). After training, the carotid artery was catheterized for AP measurements. Locomotor (tibialis anterior and gracilis) and non-locomotor skeletal muscles (temporalis) were harvested and prepared for histologic and protein expression analyses. Training increased treadmill performance by all groups (SHR = 28 percent, WKY = 64 percent, 3 days) and (SHR = 141 percent, WKY = 122 percent, 13 weeks). SHR had higher values of AP than WKY (174 ± 4 vs 111 ± 2 mmHg) that were not altered by training. Three days of running increased VEGF expression (SHR = 28 percent, WKY = 36 percent) simultaneously with an increase in capillary-to-fiber ratio in gracilis muscle (SHR = 19 percent, WKY = 15 percent). In contrast, 13 weeks of training increased gracilis capillary-to-fiber ratio (SHR = 18 percent, WKY = 19 percent), without simultaneous changes in VEGF expression. Training did not change VEGF expression and capillarity of temporalis muscle. We conclude that training stimulates time- and tissue-dependent VEGF protein expression, independent of pressure levels. VEGF triggers angiogenesis in locomotor skeletal muscle shortly after the exercise starts, but is not involved in the maintenance of capillarity after long-term exercise in female rats.

The Effect of Combined Immunosuppressive Treatment with FK 506-Cyclophosphamide on Surgical Angiogenesis / 대한정형외과연구학회지

PURPOSE: To evaluate the effect of combined immunosuppressive treatment with FK 506-cyclophosphamide on surgical angiogenesis in non-vascularized bone xenografts. MATERIALS AND METHODS: Twenty-seven hamster-to-rat non-vascularized bone xenografts were performed. For surgical angiogenesis, recipient origin saphenous arteriovenous bundles were implanted into the medullary canals of graft bones. Immunosuppression with FK 506-cyclophosphamide was performed in group 1, not in group 2, control group. At postoperative 4 weeks, microangiography with microfil was conducted. Decalcified bones were cleared and the area of newly formed capillary, capillary density, were quantitatively evaluated using Scion image program. Bone specimens stained with hematoxylin-eosin were evaluated histologically also. RESULTS: There was no significant difference of capillary densities between immunosuppressed group and non-immunosuppressed control group (0.37+/-0.03/0.39+/-0.02, P=0.58). On histological examination, both groups showed neoangiogenesis into the medullary canals and endosteal bones. CONCLUSION: FK 506-cyclophosphamide immunosuppression did not suppress the angiogenesis in non-vascularized bone xenografts, FK 506-cyclophosphamide combination of immunosuppression will be useful even in the condition of surgical angiogenesis.

The Effect of Combined Immunosuppressive Treatment with FK 506-Cyclophosphamide on Surgical Angiogenesis / 대한정형외과연구학회지

PURPOSE: To evaluate the effect of combined immunosuppressive treatment with FK 506-cyclophosphamide on surgical angiogenesis in non-vascularized bone xenografts. MATERIALS AND METHODS: Twenty-seven hamster-to-rat non-vascularized bone xenografts were performed. For surgical angiogenesis, recipient origin saphenous arteriovenous bundles were implanted into the medullary canals of graft bones. Immunosuppression with FK 506-cyclophosphamide was performed in group 1, not in group 2, control group. At postoperative 4 weeks, microangiography with microfil was conducted. Decalcified bones were cleared and the area of newly formed capillary, capillary density, were quantitatively evaluated using Scion image program. Bone specimens stained with hematoxylin-eosin were evaluated histologically also. RESULTS: There was no significant difference of capillary densities between immunosuppressed group and non-immunosuppressed control group (0.37+/-0.03/0.39+/-0.02, P=0.58). On histological examination, both groups showed neoangiogenesis into the medullary canals and endosteal bones. CONCLUSION: FK 506-cyclophosphamide immunosuppression did not suppress the angiogenesis in non-vascularized bone xenografts, FK 506-cyclophosphamide combination of immunosuppression will be useful even in the condition of surgical angiogenesis.

BASAL GENE EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR-RELATED TRANSCRIPTIONAL FACTORS IN RAT SKELETAL MUSCLE DIFFERS BETWEEN SLOW AND FAST FIBER TYPES / 体力科学

Skeletal muscle is comprised of multiple fiber types. Slow-twitch oxidative muscle fibers have greater capillary density compared with fast-twitch glycolytic fibers of skeletal muscle. To gain insight into the molecular mechanism underlying the difference of capillary density, we investigated whether the basal gene expression of vascular endothelial growth factor (VEGF), a major angiogenesis-related factor, and its transcriptional factors (hypoxia-inducible factor-1α, transforming growth factor-β1, c-jun, and c-fos) differs between these two fiber types of rat skeletal muscle. The mRNA expression of VEGF and its transcriptional factors was significantly higher in slow type fiber of muscle (soleus muscle) compared with fast type fiber of muscle (plantaris and tibialis anterior muscles). These results suggest that the difference of basal gene expression of VEGF and its transcriptional factors between slow and fast fiber types of skeletal muscle may partly contribute to the difference in capillary density between these two fiber types.