Optical coherence tomography angiography findings in patients with branch retinal vein occlusion treated with Anti-VEGF / Achados de angiografia por tomografia de coerência óptica em pacientes com oclusão de ramo da veia retiniana tratada com anti-VEGF

ABSTRACT Purpose: To investigate retinal microvasculature changes in patients treated with anti-VEGF for macular edema secondary to branch retinal vein occlusion. Methods: We examined 38 eyes of 19 patients for the study. We measured superficial and deep capillary plexus vessel densities (%), foveal avascular zone areas (mm2), and central macular thicknesses. Results: Parafoveal superficial and deep capillary plexus values were significantly lower in eyes with branch retinal vein occlusion than in fellow eyes (p<0.001). We found a significant increase in parafoveal deep capillary plexus values after the anti-VEGF treatment (p=0.032). The mean foveal avascular zone was larger in eyes with branch retinal vein occlusion than in control eyes (p<0.001). The mean central macular thickness was significantly higher in eyes with branch retinal vein occlusion than in controls, and we observed a significant decrease in central macular thickness after anti-VEGF treatment (<0.001). In addition, the cystic structures in the deep capillary plexus regressed. Conclusion: Optical coherence tomography angiography enables qualitative and quantitative evaluations during follow-up of patients treated for branch retinal vein occlusion.

RESUMO Objetivo: Investigar as alterações na microvascu latura da retina em pacientes tratados com anti-VEGF para ede ma macular secundário à oclusão de ramo da veia retiniana. Métodos: Foram examinados 38 olhos de 19 pacientes para o estudo. Medimos as densidades dos vasos do plexo capilar superficial e profunda (%), áreas da zona avascular foveal (mm2) e espessura macular central. Resultados: Os valores do plexo capilar superficial e profundo parafoveal foram significativamente menores nos olhos com oclusão de ramo da veia retiniana do que nos outros olhos (p<0,001). Encontramos um aumento significativo nos valores de plexo capilar profundo parafoveal após o tratamento com anti-VEGF (p=0,032). A zona avascular foveal média foi maior nos olhos com oclusão de ramo da veia retiniana do que nos olhos controle (p<0,001). A espessura macular central média foi significativamente maior nos olhos com oclusão de ramo da veia retiniana do que nos controles, e observamos uma diminuição significativa na espessura macular central após o tratamento com anti-VEGF (< 0,001). Além disso, as estruturas císticas no plexo capilar profundo regrediram. Conclusão: A angiotomografia de coerência óptica permite avaliações qualitativas e quantitativas durante o acompanhamento de pacientes tratados por oclusão de ramo da veia retiniana.

Histological modification in TRAM flap in rats treated with pentoxifylline

PURPOSE: To investigate the blood vessels' concentration in TRAM flap's rat model, in the presence of pentoxifylline. METHODS: 32 male, Wistar-EPM rats were divided into two groups. Control group (C): 0.5 ml of saline, intraperitoneally, once a day, for seven days before flap elevation; PTX group (P): pentoxifylline (20mg/kg/day), intraperitoneally, for seven days before flap elevation. After that, they were submitted to a caudal unipedicle TRAM flap. On the fifth postoperative day, percentages of flap necrosis were determined via the "paper template" method and Tram flap's zone IV skin biopsies were taken for histological analysis. RESULTS: the mean percentage of flap necrosis in group C was 58.7 % and in group P, 31.1 (Wilcoxon test; p = 0.003). Mean capillary vessels number in zone IV's skin in C group was 33.4 and in P group was 71.9 (p=0.008). CONCLUSIONS: Pentoxifylline was effective reducing the necrosis in the caudal unipedicle TRAM flap in the rat as well as increasing the number of capillaries in an ischemic zone (zone IV). .

Acute and subchronic toxicological evaluation of Echinophora platyloba DC (Apiaceae) total extract in Wistar rats

OBJECTIVE: Echinophora platyloba DC is a widely used herbal medicine and food seasoning in Iran. It is claimed to exert antimicrobial, antifungal, and antispasmodic effects. Despite the prevalent use of this plant as a food and medicine, there are no reports on its possible toxic effects. To evaluate the safety of E. platyloba, we tested its acute and sub-chronic toxicity in male and female Wistar rats. METHODS: Rats were orally treated with four different single doses of E. platyloba total extract and screened for signs of toxicity two weeks after administration. In the sub-chronic toxicity study, E. platyloba was administered for 45 days. Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histological markers were monitored during the study. RESULTS: We found no mortality and no abnormality in clinical signs, body weight, or necropsy findings in any of the animals in the acute study. The results of the subchronic study showed no significant difference in hematological parameters in either sex. There was a significant increase in lactate dehydrogenase in the female groups. A significant increase in the relative lung weight of female rats was noted at 500 mg/kg. Histopathological examinations revealed intra-alveolar hemorrhage in the male rats (500 mg/kg). In the females, congestion of the alveolar capillaries (at 500 mg/kg) and liver bridging necrosis (at 200 mg/kg) were significantly increased. CONCLUSION: The no observed adverse effect level of E. platyloba was determined to be 200 and 50 mg/kg for male and female rats, respectively.

Blood loss and transcapillary refill in uncontrolled treated hemorrhage in dogs

Objetive: This study evaluated retroperitoneal hematomas produced by bilateral injury of iliac arteries (uncontrolled hemorrhage), blood volume loss, transcapillary refill, the effects of volume replacement on retroperitoneal bleeding and the hemodynamic changes with and without treatment. Methods: Initial blood volume was determined with Tc99m-labelled red cells, and bleeding was evaluated by means of a portable scintillation camera positioned over the abdomen. Previously splenectomized mongrel dogs (16.8 ± 2.2 kg) were submitted to hemorrhage for 30 minutes and randomized into three groups: I - no treatment (n=7); II - treatment with 32 mL/kg of Lactated Ringer's for three to five minutes (n=7); and III - treatment with 4 mL/kg of 7.5 percent NaCl plus 6.0 percent dextran 70 for three to five minutes (n=7). They were studied for an additional 45 minutes. Results: Volume replacement produced transitory recovery in hemodynamic variables, including mean pulmonary artery pressure, pulmonary capillary wedge pressure and cardiac index, with significant increase in dogs treated with 32 mL/kg of Lactated Ringer's and 7.5 percent NaCl plus 6.0 percent dextran 70 (p<0.001, against no treatment), along with a decrease (p<0.001) in the systemic vascular resistance index. Groups II and III had significant initial decreases in hematocrit and hemoglobin. The treated dogs (groups II and III) presented rebleeding, which was greater during treatment with 32 mL/kg of Lactated Ringer's (group II). Conclusions: Despite the rebleeding observed in treated groups, the utilization of hypertonic saline solution with dextran proved to be effective in the initial reanimation, producing evident transcapillary refill, while the Lactated Ringer's solution produced capillary extravasation and was ineffective in the initial volume replacement in this model of uncontrolled hemorrhage.

Effects of buflomedil and pentoxifylline on hamster skin-flap microcirculation: prediction of flap viability using orthogonal polarization spectral imaging

OBJECTIVE: This study investigated the effects of buflomedil and pentoxifylline, both of which are used in reconstructive surgery of hamster skin flap microcirculation, and evaluated the skin flap survival rate by orthogonal polarization spectral imaging. METHOD: Twenty-four adult male Syrian golden hamsters were divided into three groups: a control (C, 0.1 ml 0.9 percent saline), buflomedil (B, 3 mg/kg/day), and pentoxifylline group (P, 14.5 mg/kg/day). Treatments administered intraperitoneally were initiated 1 hour before skin flap preparation and continued for 7 days post-operatively at 12-hour intervals. Preparations (skin flaps) were divided into 12 fields, which were organized into six bands. Functional capillary density (FCD, in mm/mm²), distance from the skin flap base to blood flow cessation (Dist with flow, in cm), percentage of viable skin (VA, in percent), and qualitative analysis of blood flow by orthogonal polarization spectral imaging were performed at 1 and 24 hours and on the seventh post-operative day. RESULT: Bands IV, V, and VI presented no flow independent of time. The functional capillary density group B was higher than that of groups C and P, primarily after 24 hours. All groups showed an increase in D with time but reached similar final distances (C = 2.73, B = 2.78 and P = 2.70 cm). Moreover, the percentage of viable areas remained at approximately 50 percent. The orthogonal polarization spectral imaging was useful to assess viability by counting fields with and without blood flow. CONCLUSIONS: Functional capillary density values were higher in the buflomedil group compared to the control and pentoxifylline groups in this model. Functional capillary density did not influence D or the percentage of VA, and the technique showed favorable potential to assess/predict the viability of skin flaps within 1 h after surgery.

Nicotine-evoked cytosolic Ca2+ increase and cell depolarization in capillary endothelial cells of the bovine adrenal medulla

Endothelial cells are directly involved in many functions of the cardiovascular system by regulating blood flow and blood pressure through Ca2+ dependent exocitosis of vasoactive compounds. Using the Ca2+ indicator Fluo-3 and the patch-clamp technique, we show that bovine adrenal medulla capillary endothelial cells (B AMCECs) respond to acetylcholine (ACh) with a cytosolic Ca2+ increase and depolarization of the membrane potential (20.3±0.9 mV; n=23). The increase in cytosolic Ca2+ induced by 10µM ACh was mimicked by the same concentration of nicotine but not by muscarine and was blocked by 100 µM of hexamethonium. On the other hand, the increase in cytosolic Ca2+ could be depressed by nifedipine (0.01 -100 µM) or withdrawal of extracellular Ca2+. Taken together, these results give evidence for functional nicotinic receptors (nAChRs) in capillary endothelial cells of the adrenal medulla. It suggests that nAChRs in B AMCECs may be involved in the regulation of the adrenal gland's microcirculation by depolarizing the membrane potential, leading to the opening of voltage-activated Ca2+ channels, influx of external Ca2+ and liberation of vasoactive compounds.

Treatment of essential hypertension does not normalize capillary rarefaction

OBJECTIVES: To determine if capillary rarefaction persists when hypertension is treated with angiotensin converting enzyme inhibitor, thiazidic diuretic and/or beta-blocker, and to identify which microcirculatory alterations (structural and functional) persist after anti-hypertensive treatment. METHODS: We evaluated 28 well-controlled essential hypertensive patients and 19 normotensive subjects. Nailfold videocapillaroscopy examination of the fourth finger of the left hand was used to determine the functional capillary densities at baseline, during post-occlusive hyperemia, and after venous congestion. Capillary loop diameters (afferent, apical and efferent) and red blood cell velocity were also quantified. RESULTS: Compared with normotensive subjects, hypertensive patients showed lower mean functional capillary density at baseline (25.1±1.4 vs. 33.9±1.9 cap/mm², p<0.01), during post-occlusive reactive hyperemia (29.3±1.9 vs. 38.2±2.2 cap/mm², p<0.01) and during venous congestion responses (31.4±1.9 vs. 41.1±2.3 cap/mm², p<0.01). Based on the density during venous congestion, the estimated structural capillary deficit was 25.1 percent. Mean capillary diameters were not different at the three local points, but red blood cell velocity at baseline was significantly lower in the hypertensive group (0.98±0.05 vs. 1.17±0.04 mm/s, p<0.05). CONCLUSIONS: Patients treated for essential hypertension showed microvascular rarefaction, regardless of the type of therapy used. In addition, the reduced red blood cell velocity associated with capillary rarefaction might reflect the increased systemic vascular resistance, which is a hallmark of hypertension.

Effect of vasoactive drugs on muscle fibre types and capillares

The effect of nitroglycerin, nifedipine, diltiazem or propranolol on fibre types and capillaries was studied in extensor digitorum longus (EDL) and soleus (S) muscles of the rat. In EDL muscle nifedipine increased the proportion of type I fibres (7.9 percent +/- 1.7 vs. 4.7 percent +/- 2.7). Nitroglycerin and dialtiazem decreased IIB fibres (40.7 percent +/- 10.6 and 37.3 percent +/- 14.6 respectively vs. 52.3 percent +/- 9.4). Propranolol increased IIB fibres to 66.3 percent +/- 8.1, while reducing IIA fibres (25.3 percent +/- 6.6 vs. 42.2 percent +/- 6.9). No changes in fibre type proportion were found in S muscle. Capillary density was increased in EDL by nitroglycerin (965 +/- 171 vs. 818 +/- 98 cap/mm2). Propranolol had a dual effect on this parameter, decreasing it in EDL to 570 +/- 85 and augmenting it in S (754 +/- 117 vs. 601 +/- 121). No change was found in capillary to fibre ratio with any of the drugs either in EDL or S muscles. In EDL all the drugs except propranolol, which had the opposite effect, decreased the area of IIA fibre per capillary around 20 percent this effect can be interpreted as a reduction of diffusion distance from blood to fibre