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1.
Med Sci Monit ; 25: 6313-6321, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31437131

RESUMO

BACKGROUND To explore the protective effects of Shexiang Tongxin Dropping Pill (STP) in improving peripheral microvascular dysfunction in mice and to explore the involved mechanism. MATERIAL AND METHODS A peripheral microvascular dysfunction model was established by combined myocardial infarction (MI) and lipopolysaccharide (LPS) injection in mice. Then, the mice were randomized into a model group (n=10) or an STP group (n=10), which were treated with normal saline and STP, respectively. The cremaster muscle microvascular blood flow velocity and numbers of leukocytes adherent to the venular wall were evaluated before and after drug intervention. We assessed the expression of adhesion molecule CD11b and related transcript factor FOXO1 in leukocytes, cystathionine-γ-lyase (CSE) mRNA expression in the cremaster muscle, and mitochondrial DNA copy numbers. RESULTS Compared with those of control mice, the cremaster microvascular blood flow velocity, cremaster CSE expression, and mitochondrial DNA copy number in mice from the model group were significantly lower and leukocyte adhesion and CD11b and FOXO1 expression were significantly higher. Intervention with STP could significantly increase the cremaster microvascular flow velocity (0.480±0.010 mm/s vs. 0.075±0.005 mm/s), mRNA expression of cremaster CSE, and mitochondrial DNA copy number, but it inhibited leukocyte adhesion and decreased leukocyte CD11b and FOXO1 expression. CONCLUSIONS STP significantly improved peripheral microcirculation, in which increased CSE expression might be the underlying mechanism.


Assuntos
Cistationina gama-Liase/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Microvasos/efeitos dos fármacos , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Antígeno CD11b/análise , Adesão Celular/efeitos dos fármacos , Cistationina gama-Liase/análise , Medicamentos de Ervas Chinesas/metabolismo , Proteína Forkhead Box O1/análise , Sulfeto de Hidrogênio/farmacologia , Leucócitos/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microcirculação/efeitos dos fármacos , Músculos/irrigação sanguínea , Distribuição Aleatória , Fluxo Sanguíneo Regional/efeitos dos fármacos
2.
J Trauma Acute Care Surg ; 85(3): 512-518, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29847535

RESUMO

BACKGROUND: New strategies to mitigate ischemia during REBOA and to prolong its maximal duration are needed. We hypothesized that simple external cooling of the hind limbs would decrease ischemia-reperfusion injury following prolonged Zone 3 REBOA. METHODS: Twelve swine were anesthetized, instrumented, splenectomized, and then underwent 15% total blood volume hemorrhage. Animals were randomized to hypothermia or control followed by 4 hours of Zone 3 REBOA, resuscitation with shed blood, and 3 hours of critical care. Physiologic parameters were continuously recorded, and laboratory specimens were obtained at regular intervals. Baseline and end-of-study muscle biopsies were obtained for histologic analysis. RESULTS: There were no significant differences between groups at baseline or after hemorrhage. Maximum creatine kinase was significantly lower in the hypothermia group compared with the normothermia group (median [interquartile range] = 3,445 U/mL [3,380-4,402 U/mL] vs. 22,544 U/mL [17,030-24,981 U/mL]; p < 0.01). Maximum serum myoglobin was also significantly lower in the hypothermia group (1,792 ng/mL [1,250-3,668 ng/mL] vs. 21,186 ng/mL [14,181-24,779 ng/mL]; p < 0.01). Fascial compartment pressures were significantly lower during critical care in the hypothermia group (p = 0.03). No histologic differences were observed in hind limb skeletal muscle. CONCLUSIONS: External cooling during prolonged Zone 3 REBOA decreased ischemic muscle injury and resulted in lower compartment pressures following reperfusion. Hypothermia may be a viable option to extend the tolerable duration of Zone 3 occlusion, beyond what is currently achievable. Future survival studies are required to assess functional outcomes.


Assuntos
Temperatura Baixa/efeitos adversos , Procedimentos Endovasculares/instrumentação , Extremidade Inferior/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Animais , Oclusão com Balão/métodos , Creatina Quinase/metabolismo , Modelos Animais de Doenças , Feminino , Hemorragia/prevenção & controle , Membro Posterior/irrigação sanguínea , Membro Posterior/fisiopatologia , Hipotermia/complicações , Isquemia , Extremidade Inferior/fisiopatologia , Masculino , Músculos/irrigação sanguínea , Músculos/metabolismo , Músculos/patologia , Mioglobina/sangue , Reperfusão/efeitos adversos , Ressuscitação/instrumentação , Choque Hemorrágico , Suínos
3.
Int J Nanomedicine ; 13: 1819-1829, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29606873

RESUMO

Background: Endothelial progenitor cells (EPCs) play an important role in repairing ischemia tissues. However, the survival, migration and therapeutic efficacy of EPCs after transplantation need to be better understood for further cell therapy. Purpose: This study investigated the migration effect of EPCs labeled with a multimodal imaging agent in a murine ischemic hindlimb model, using magnetic resonance imaging (MRI) and optical imaging after transplantation. Methods: EPCs derived from mouse bone marrow were labeled with a multimodal imaging agent and were administered through intracardiac delivery to mice with ischemic hindlimbs. The injected EPCs and their migration effect were observed via MRI and optical imaging in vivo, and then compared to a reference standard based on histological data. The quantification of gadolinium in tissue samples was done using inductively coupled plasma mass spectrometry (ICP-MS). Results: Using in vivo MRI and optical imaging, the labeled EPCs were observed to migrate to ischemic muscle on days 3-5 after injection, while ex vivo, the EPCs were observed in the capillary vessels of the injured tissue. There were significant linear correlations between the Gd contents measured using ICP-MS in samples from the ischemic hindlimbs and livers and T1 relaxation times calculated using MRI, as well as the average fluorescence signal intensities recorded in optical images (T1 relaxation time: r=0.491; average signal from optical imaging: r=0.704, P<0.01). EPC treatment upregulated the levels of C-X-C chemokine receptor 4 and vascular endothelial growth factor (VEGF) receptor 2 and enhanced the expression of stromal cell-derived factor-1 and VEGF. Conclusion: Transplanted EPCs can be monitored with noninvasive MRI and optical imaging in vivo and were found to enhance the paracrine secretion of angiogenic factors.


Assuntos
Movimento Celular , Células Progenitoras Endoteliais/citologia , Células Progenitoras Endoteliais/transplante , Isquemia/terapia , Imagem Multimodal , Músculos/irrigação sanguínea , Músculos/patologia , Animais , Células da Medula Óssea/citologia , Forma Celular , Terapia Baseada em Transplante de Células e Tecidos , Citosina Desaminase/metabolismo , Membro Posterior/irrigação sanguínea , Membro Posterior/patologia , Raios Infravermelhos , Isquemia/patologia , Fígado/patologia , Imagem por Ressonância Magnética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Nus , Neovascularização Fisiológica , Imagem Óptica , Fenótipo , Polilisina/química
4.
J Tissue Eng Regen Med ; 12(1): e486-e494, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-27689683

RESUMO

Shock wave therapy (SWT) has been shown to induce angiogenesis in ischaemic muscle. However, the mechanism of action remains unknown. Macrophages are crucial for angiogenic responses after ischaemic injury. The M2 macrophage subset enables tissue repair and induces angiogenesis. It was hypothesized that the angiogenic effects of SWT are at least partly caused by enhanced macrophage recruitment. C57BL/6 mice were subjected to hind limb ischaemia with subsequent SWT or sham treatment. Muscles were analysed via immunofluorescence staining, reverse-transcription polymerase chain reaction and western blot. Gene expression and proteins involved in macrophage recruitment were analysed and tissue sections were stained for macrophages, including subsets, capillaries and arterioles. Laser Doppler perfusion imaging was performed to assess functional outcome. Treated muscles showed increased expression of the pivotal macrophage recruiting factor monocyte chemotactic protein 1 (MCP-1). Higher levels of macrophage marker CD14 were found. Increased numbers of macrophages after SWT could be confirmed by immunofluorescence staining. The expression of the M2 polarization promoting chemokine interleukin 13 was significantly elevated in the treatment group. Elevated mRNA expression of the M2 scavenger receptor CD163 was found after SWT. Immunofluorescence staining confirmed increased numbers of M2 macrophages after treatment. It was found that SWT resulted in higher number of capillaries and arterioles. Assessment of functional outcome revealed significantly improved limb perfusion in treated animals. Shock wave therapy causes increased macrophage recruitment and enhanced polarization towards reparative M2 macrophages in ischaemic muscle resulting in angiogenesis and improved limb perfusion and therefore represents a promising new treatment option for the treatment of ischaemic heart disease. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Ondas de Choque de Alta Energia , Membro Posterior/irrigação sanguínea , Isquemia/terapia , Macrófagos/metabolismo , Perfusão , Animais , Arteríolas/patologia , Capilares/patologia , Contagem de Células , Polaridade Celular , Isquemia/patologia , Masculino , Camundongos Endogâmicos C57BL , Músculos/irrigação sanguínea , Músculos/patologia
5.
Physiol Meas ; 39(1): 015003, 2017 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-29161235

RESUMO

OBJECTIVE: In neonates, a patent ductus arteriosus (DA) may be associated with severe complications. We used near-infrared spectroscopy (NIRS) with venous occlusion to investigate the influence of an open DA on peripheral muscle oxygenation/perfusion in preterm neonates. APPROACH: We analyzed secondary outcome parameters collected as part of prospective observational studies. NIRS measurements were performed between the first and third day of life. Arterial oxygen saturation (SaO2) and heart rate (HR) were monitored by pulse oximetry on the ipsilateral foot. Venous occlusion was performed with a blood pressure cuff on the thigh. Tissue oxygenation index (TOI), hemoglobin flow (Hbflow), oxygen delivery (DO2), oxygen consumption (VO2), mixed venous oxygenation (SvO2), and fractional oxygen extraction (FOE) were assessed. Echocardiography was performed within plus/minus 6 h from NIRS measurements. MAIN RESULTS: Twenty-eight neonates were included. In neonates with open DA (n = 15), the FOE was significantly higher (p = 0.046). DA diameter correlated negatively with SvO2 (r = -0.413, p = 0.032) and positively with FOE (r = 0.417, p = 0.030). In neonates with open DA, SaO2 was significantly lower (p = 0.041). DA diameter correlated negatively with SaO2 (r = -0.377, p = 0.048) and positively with HR (r = 0.489, p = 0.010). SIGNIFICANCE: Our results showed that an open DA influences peripheral muscle oxygenation in preterm neonates.


Assuntos
Canal Arterial/fisiologia , Músculos/irrigação sanguínea , Músculos/metabolismo , Oxigênio/metabolismo , Feminino , Hemoglobinas/metabolismo , Humanos , Recém-Nascido , Masculino
6.
J Cardiothorac Vasc Anesth ; 31(6): 2065-2071, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28693932

RESUMO

OBJECTIVE: To investigate whether changes in muscle tissue perfusion measured with positron emission tomography would be reflected by parallel changes in muscle tissue oxygen saturation (StO2) measured using near-infrared spectroscopy during high and low blood flow levels achieved using cardiopulmonary bypass (CPB) in an animal model. DESIGN: A prospective, randomized study. SETTING: Research laboratory, single institution. PARTICIPANTS: Eight pigs (69-71 kg). INTERVENTIONS: In anesthetized pigs, normothermic CPB was established with a blood flow of 60 mL/kg/min for 1 hour. Thereafter, a low blood flow of either 47.5 or 35 mL/kg/min was applied for 1 hour followed by a blood flow of 60 mL/kg/min for an additional hour. Regional StO2 was measured continuously by placing a near-infrared spectroscopy electrode on the skin above the gracilis muscle of the noncannulated back leg. Muscle tissue perfusion was measured using positron emission tomography with 15O-labeled water during spontaneous circulation and the different CPB blood flows. Systemic oxygen consumption was estimated by measurement of venous saturation and lactate levels. MEASUREMENTS AND MAIN RESULTS: The results showed profound systemic ischemia during low CPB blood flow. StO2 remained high until muscle tissue perfusion decreased to about 50%, after which StO2 paralleled the linear decrease in muscle tissue perfusion. CONCLUSION: In an experimental CPB animal model, StO2 was stable until muscle tissue perfusion was reduced by about 50%, and at lower blood flow levels, there was almost a linear relationship between StO2 and muscle tissue perfusion.


Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Ponte Cardiopulmonar/efeitos adversos , Hemodinâmica/fisiologia , Músculos/irrigação sanguínea , Músculos/fisiologia , Consumo de Oxigênio/fisiologia , Animais , Ponte Cardiopulmonar/tendências , Circulação Cerebrovascular/fisiologia , Feminino , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/fisiologia , Distribuição Aleatória , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Suínos
7.
Blood Cells Mol Dis ; 65: 56-59, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28552472

RESUMO

While sickle cell disease (SCD) is characterized by frequent vaso-occlusive crisis (VOC), no direct observation of such an event in skeletal muscle has been performed in vivo. The present study reported exacerbated in vivo metabolic changes suggestive of a spontaneous muscular VOC in exercising muscle of a sickle cell mouse. Using magnetic resonance spectroscopy of phosphorus 31, phosphocreatine and inorganic phosphate concentrations and intramuscular pH were measured throughout two standardized protocols of rest - exercise - recovery at two different intensities in ten SCD mice. Among these mice, one single mouse presented divergent responses. A statistical analysis (based on confidence intervals) revealed that this single mouse presented slower phosphocreatine resynthesis and inorganic phosphate disappearance during the post-stimulation recovery of one of the protocols, what could suggest an ischemia. This study described, for the first time in a sickle cell mouse in vivo, exacerbated metabolic changes triggered by an exercise session that would be suggestive of a live observation of a muscular VOC. However, no evidence of a direct cause-effect relationship between exercise and VOC has been put forth.


Assuntos
Anemia Falciforme/complicações , Anemia Falciforme/metabolismo , Músculos/irrigação sanguínea , Músculos/metabolismo , Condicionamento Físico Animal , Doenças Vasculares/etiologia , Anemia Falciforme/diagnóstico , Animais , Biomarcadores , Modelos Animais de Doenças , Progressão da Doença , Imagem por Ressonância Magnética , Masculino , Camundongos , Doenças Vasculares/patologia
8.
Blood Cells Mol Dis ; 65: 23-28, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28411485

RESUMO

The present study investigated cerebral and muscle hemoglobin oxygen saturation (tissue oxygen index, TOI) in children with sickle cell anemia (SS), sickle cell hemoglobin C disease (SC) and healthy children (AA). TOI was measured by near-infrared spectroscopy (NIRS) and spectral analysis of the TOI variability was used to assess flowmotion and vasomotion. Arterial oxyhemoglobin saturation (SpO2), hemorheological and hematological parameters were also measured in SS and SC children. Both TOI were lower in SS compared to both AA and SC children, with SC exhibiting lower values than AA children. Cerebral vasomotion expressed in absolute values was enhanced in SS compared to AA and SC children. Muscle vasomotion did not differ between the three groups. Hematocrit, SpO2 and red blood cell deformability were positively associated with cerebral TOI in SS children. We demonstrated that 1) cerebral and muscle TOI were markedly decreased in SS children while the decrease of TOI was milder in SC children, 2) cerebral TOI level was associated with several biological markers in SS children only and 3) cerebral vasomotion was enhanced in SS, possibly to counterbalance the effects of chronic cerebral hypoxia.


Assuntos
Anemia Falciforme/metabolismo , Anemia Falciforme/fisiopatologia , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/metabolismo , Músculos/irrigação sanguínea , Músculos/metabolismo , Oxigênio/metabolismo , Adolescente , Anemia Falciforme/sangue , Anemia Falciforme/genética , Criança , Deformação Eritrocítica , Feminino , Genótipo , Hematócrito , Hemodinâmica , Hemoglobina Falciforme/genética , Hemorreologia , Humanos , Masculino , Consumo de Oxigênio , Espectroscopia de Luz Próxima ao Infravermelho
9.
Sci Rep ; 7(1): 770, 2017 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-28396600

RESUMO

Here we investigated whether endothelial colony forming cells (ECFC) and mesenchymal progenitor cells (MPC) form vascular networks and restore blood flow in ischemic skeletal muscle, and whether host myeloid cells play a role. ECFC + MPC, ECFC alone, MPC alone, or vehicle alone were injected into the hind limb ischemic muscle one day after ligation of femoral artery and vein. At day 5, hind limbs injected with ECFC + MPC showed greater blood flow recovery compared with ECFC, MPC, or vehicle. Tail vein injection of human endothelial specific Ulex europaeus agglutinin-I demonstrated an increased number of perfused human vessels in ECFC + MPC compared with ECFC. In vivo bioluminescence imaging showed ECFC persisted for 14 days in ECFC + MPC-injected hind limbs. Flow cytometric analysis of ischemic muscles at day 2 revealed increased myeloid lineage cells in ECFC + MPC-injected muscles compared to vehicle-injected muscles. Neutrophils declined by day 7, while the number of myeloid cells, macrophages, and monocytes did not. Systemic myeloid cell depletion with anti-Gr-1 antibody blocked the improved blood flow observed with ECFC + MPC and reduced ECFC and MPC retention. Our data suggest that ECFC + MPC delivery could be used to reestablish blood flow in ischemic tissues, and this may be enhanced by coordinated recruitment of host myeloid cells.


Assuntos
Células Progenitoras Endoteliais/citologia , Isquemia/fisiopatologia , Células-Tronco Mesenquimais/citologia , Músculos/irrigação sanguínea , Neovascularização Fisiológica , Fluxo Sanguíneo Regional , Animais , Células Progenitoras Endoteliais/metabolismo , Membro Posterior/irrigação sanguínea , Humanos , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Músculo Esquelético/irrigação sanguínea , Células Mieloides/citologia , Células Mieloides/metabolismo
10.
Nucl Med Biol ; 46: 25-31, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27984781

RESUMO

INTRODUCTION: Peripheral artery disease can lead to severe disability and limb loss. Therapeutic strategies focussing on macrovascular repair have shown benefit but have not significantly reduced amputation rates in progressive PAD. Proangiogenic small molecule therapies may substantially improve vascularisation in limb ischemia. The purpose of the current study was to assess the proangiogenic effects of simvastatin in a murine model of hind limb ischemia using longitudinal multimodal imaging. METHODS: Mice underwent surgical intervention to induce hind limb ischemia, and were treated with simvastatin orally for 28days. Neovascularisation was assessed using 99mTc-RGD SPECT imaging, and macrovascular volume was assessed by quantitative time of flight MRI. At each imaging time point, VEGF expression and capillary vessel density were quantified using immunohistochemical analysis. RESULTS: Simvastatin significantly increased 99mTc-RGD retention in the ischemic hind limb by day 3 post-surgery, with maximal retention at day 8. Vascular volume was significantly increased in the ischemic hind limb of simvastatin treated animals, but only by day 22. Immunohistochemical analysis shows that simvastatin significantly augmented tissue VEGF expression from day 8 with increase in capillary density (CD31+) from day 14. CONCLUSIONS: Early assessment of proangiogenic therapy efficacy can be identified using 99mTc-RGD SPECT, which displays significant increases in retention before macrovascular volume changes are measureable with MRI. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: Simvastatin offers an effective proangiogenic therapy as an adjunct for management of limb ischemia. Simvastatin induces integrin expression and vascular remodeling leading to neovascularisation and improved perfusion.


Assuntos
Membro Posterior/irrigação sanguínea , Isquemia/diagnóstico por imagem , Isquemia/fisiopatologia , Imagem Multimodal , Neovascularização Fisiológica/efeitos dos fármacos , Fluxo Sanguíneo Regional/efeitos dos fármacos , Sinvastatina/farmacologia , Animais , Capilares/efeitos dos fármacos , Capilares/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Isquemia/metabolismo , Imagem por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Músculos/irrigação sanguínea , Músculos/metabolismo , Oligopeptídeos/química , Tecnécio/química , Tomografia Computadorizada de Emissão de Fóton Único , Fator A de Crescimento do Endotélio Vascular/metabolismo
11.
Magn Reson Imaging ; 34(7): 875-88, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27071310

RESUMO

Transverse relaxation rates for Carr-Purcell-Meiboom-Gill (CPMG) sequences increase with inter-echo time in presence of microscopic magnetic field inhomogeneities due to nuclear spin diffusion. For a weak field approximation that includes diffusion effects, the CPMG relaxation rate shift for proton diffusion around capillaries in muscle tissue can be expressed in terms of a frequency correlation function and the inter-echo time. The present work provides an analytical expression for the local relaxation rate shift that is dependent on local blood volume fraction, diffusion coefficient, capillary radius, susceptibility difference and inter-echo time. Asymptotic regions of the model are in agreement with previous modeling results of Brooks et al., Luz et al. and Ziener et al. In comparison with simulation data, the model shows an equal or better accuracy than established approximations. Also, model behavior coincides with experimental data for rat heart and skeletal muscle. The present work provides analytical tools to extract sub-voxel information about uniform capillary networks that can be used to study capillary organization or micro-circulatory remodeling.


Assuntos
Capilares/fisiologia , Imagem de Difusão por Ressonância Magnética/métodos , Músculos/irrigação sanguínea , Animais , Modelos Cardiovasculares , Modelos Teóricos , Prótons , Ratos , Remodelação Vascular/fisiologia
12.
Eur Rev Med Pharmacol Sci ; 20(6): 1192-202, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27049277

RESUMO

OBJECTIVE: Thymoquinone (TQ) is an antioxidant and anti-apoptotic substance found in the Nigella sativa plant. Alpha-tocopherol (α-TP) is a potent antioxidant. We aimed to determine whether or not TQ and TP have a protective effect against lower limb ischemia-reperfusion (IR) injury of muscle and the sciatic nerve. MATERIALS AND METHODS: A single dose of TQ 25 mg/kg was given intraperitoneally to the TQ group, a single dose of α-TP 200 mg/kg was given intraperitoneally to the α-TP group. IR was performed for 45 minutes after the drugs' applications. RESULTS: While serum levels of malondialdehyde (MDA) and interleukin-6 (IL-6) of the IR group were significantly higher than those of the TQ plus α-TP, TQ and α-TP groups (p<0.001, p<0.001, p=0.008, respectively) and IL-6 (all p<0.001), the reduced glutathione (GSH) level of the IR group was lower than that of the other three groups. While neuronal nitric oxide synthase activity of nerve tissues of the IR group was significantly lower than that of the TQ plus α-TP group, the muscle tissue caspase-3 activity was higher than that of the TQ plus α-TP group. CONCLUSIONS: Administration of TQ plus α-TP may strongly protect muscle and nerve tissues against IR injury via their synergistic effects.


Assuntos
Benzoquinonas/uso terapêutico , Extremidade Inferior/irrigação sanguínea , Músculos/irrigação sanguínea , Nigella sativa/metabolismo , Nervo Isquiático/efeitos dos fármacos , alfa-Tocoferol/uso terapêutico , Animais , Antioxidantes/farmacologia , Benzoquinonas/administração & dosagem , Benzoquinonas/farmacologia , Masculino , Ratos , Ratos Wistar , Traumatismo por Reperfusão , alfa-Tocoferol/administração & dosagem , alfa-Tocoferol/farmacologia
13.
Thromb Res ; 141: 106-11, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26994683

RESUMO

BACKGROUND: Human cord blood (CB) endothelial colony forming cells (ECFCs) are endowed with high vascular regenerative ability in immunodeficient mice, but their immunogenicity and susceptibility to rejection in immunocompetent models has yet to be explored. METHODS: We injected CB ECFCs in non-immuno-suppressed C57BL/6J mice after having induced the hindlimb ischemia and we investigated their contribution to the recovery from the ischemic injury. Human ECFCs (hECFCs) were administered by intramuscular injection and hindlimb blood perfusion was measured by laser Doppler analysis at 7-day intervals for 28days after treatment. Mice were sacrificed after 7 and 28days and immunohistochemistry for specific human (CD31) and mouse (von Willebrand factor) endothelial antigens was carried out. Before euthanasia, blood samples to assess cytokines and angiogenic growth factor levels were collected. RESULTS: Mice injected with hECFCs showed a prompter and greater recovery of blood flow than controls. Several endothelial cells of human origin were detected at day7 after injection and their number declined progressively. Likewise, a progressive increase of mouse-derived vascular structures were observed, paralleled by the amplified endogenous production of various soluble mediators of angiogenesis, including Vascular Endothelial Growth Factor and Fibroblast Growth Factor. CONCLUSIONS: Overall, our findings are consistent with the hypothesis that human ECFCs might expand the endogenous vascular repair potential of recipients and support their possible HLA-independent unconventional use.


Assuntos
Células Progenitoras Endoteliais/transplante , Sangue Fetal/citologia , Membro Posterior/irrigação sanguínea , Isquemia/terapia , Neovascularização Fisiológica , Animais , Citocinas/sangue , Modelos Animais de Doenças , Células Progenitoras Endoteliais/citologia , Membro Posterior/patologia , Humanos , Isquemia/sangue , Isquemia/patologia , Camundongos Endogâmicos C57BL , Músculos/irrigação sanguínea , Músculos/patologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Fator de von Willebrand/análise
14.
J Surg Res ; 201(2): 440-5, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27020830

RESUMO

BACKGROUND: Extracorporeal shock wave therapy (ESWT) is mainly applied in tendon as well as bone problems based on stem-cell activation and healing acceleration. The effect of ESWT on muscle tissue is much less understood to date. However, from a clinical perspective, muscle injuries are of distinct interest especially in elite athletes such as soccer players. MATERIAL AND METHODS: A total of 26 rats were randomized into two groups. Group A received a single application of high-energetic focused ESWT (0.3 mJ/mm(2), 4 Hz, 1000 impulses, 10 J), whereas group B underwent the same procedure every 10 min for three sessions (3 × 0.3 mJ/mm(2), 4 Hz, 3 × 1000 impulses, totaling 30 J). Blood flow at a depth of 8 mm was measured continuously and noninvasively by a combined Laser-Doppler-Imaging and photospectrometric technique (Oxygen-to-see, O2C, LEA Medizintechnik, Germany). RESULTS: One minute after the application of high-energy ESWT blood flow in group A increased by 16.5% (P = 0.007). Thereafter, it decreased from minute 2 after application and remained significantly unchanged to baseline value until the end of the measuring period at 50 min (P = 0.550). Group B showed a similar significant increase in blood flow of 16.4% (P = 0.049) and a decrease afterward, too. After the second focused ESWT blood flow was boosted to 26.6% (P = 0.004), remaining significantly elevated until the third application was initiated. Muscular blood flow was increased to 29.8% after the third focused ESWT (P < 0.001), remaining significantly increased for another 10 min. CONCLUSIONS: Focused ESWT enhances blood flow in the muscle of rats. Moreover, repetitive ESWT extended this beneficial effect.


Assuntos
Ondas de Choque de Alta Energia/uso terapêutico , Microcirculação , Músculos/irrigação sanguínea , Animais , Distribuição Aleatória , Ratos Sprague-Dawley
15.
Microvasc Res ; 104: 11-22, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26576829

RESUMO

BACKGROUND: The use of wavelengths of the near-infrared region by near-infrared spectroscopy (NIRS) has been studied for several applications in vascular disease. This systematic review aims to explore the clinical relevance of monitoring muscle tissue oxygenation in vascular disease with NIRS. METHODS: A systematic search in PubMed, EMBASE, CINAHL and Cochrane databases was performed to identify clinical NIRS studies, published until April 2015, involving muscle tissue oxygenation in vascular disease. RESULTS: After screening 183 manuscripts, 38 studies (n=2010) were included. Studies concerned peripheral arterial disease (PAD) (twelve studies, n=848), compartment syndrome of lower extremities (seven studies, n=205), deep vein thrombosis (DVT) (six studies, n=429), buttock and lower extremity ischaemia in abdominal aortic aneurysm repair (six studies, n=139), free flap failure (five studies, n=354), and spinal cord ischaemia in thoracoabdominal aortic aneurysm repair (two studies, n=35). Nine studies compared NIRS with gold standards and provided cut-off values. Four studies regarding chronic compartment syndrome and DVT determined higher sensitivity (78%-97%) than specificity (56%-76%). Two studies regarding PAD and buttock claudication determined higher specificity (87%-95%) than sensitivity (33%-88%). Three studies regarding free flap failure determined sensitivity and specificity of 100%. CONCLUSION: We found sufficient evidence to use NIRS in clinical setting for assessment of chronic compartment syndrome of lower extremities, and as surveillance tool for detection of free flap failure. So far, clinical relevance of routine use of NIRS in other vascular applications is less clear. Cut-off values to discriminate are not yet unanimous and better validation has to be awaited for.


Assuntos
Músculos/irrigação sanguínea , Músculos/metabolismo , Oxigênio/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Doenças Vasculares/metabolismo , Síndromes Compartimentais/metabolismo , Retalhos de Tecido Biológico/efeitos adversos , Retalhos de Tecido Biológico/irrigação sanguínea , Humanos , Isquemia/metabolismo , Doença Arterial Periférica/metabolismo , Trombose Venosa/metabolismo
20.
Physiol Res ; 64(6): 807-19, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26047383

RESUMO

To propose a test to evaluate endothelial function, based on VO(2) on-transition kinetics in sub-anaerobic threshold (AT) constant load exercise, we tested healthy subjects and patients with ischemic-hypertensive cardiopathy by two cardiopulmonary tests on a cycle ergometer endowed with an electric motor to overcome initial inertia: a pre-test and, after at least 24 h, one 6 min constant load exercise at 90 % AT. We measured net phase 3 VO(2)-on kinetics and, by phase 2 time constant (tau), valued endothelial dysfunction. We found shorter tau in repeated tests, shorter time between first and second test, by persisting endothelium-dependent arteriolar vasodilatation and/or several other mechanisms. Reducing load to 80 % and 90 % AT did not produce significant changes in tau of healthy volunteers, while in heart patients an AT load of 70 %, compared to 80 % AT, shortened tau (delta=4.38+/-1.65 s, p=0.013). In heart patients, no correlation was found between NYHA class, ejection fraction (EF), and the two variables derived from incremental cycle cardio-pulmonary exercise, as well as between EF and tau; while NYHA class groups were well correlated with tau duration (r=0.92, p=0.0001). Doxazosin and tadalafil also significantly reduced tau. In conclusion, the O(2) consumption kinetics during the on-transition of constant load exercise below the anaerobic threshold are highly sensitive to endothelial function in muscular microcirculation, and constitute a marker for the evaluation of endothelial dysfunction.


Assuntos
Limiar Anaeróbio , Endotélio Vascular/fisiopatologia , Hipertensão/fisiopatologia , Microcirculação , Isquemia Miocárdica/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Exercício Físico/fisiologia , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculos/irrigação sanguínea
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