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1.
Medicine (Baltimore) ; 99(41): e22318, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031270

RESUMO

INTRODUCTION: The market for dietary supplements in the sports sector has been growing rapidly for several years, though there is still lacking evidence regarding their claimed benefits. One group is that of nitric oxide increasing supplements, so-called "NO-boosters," which are claimed to improve the supply of oxygen and nutrients to the muscle by enhancing vasodilation.The aim of this study was to investigate 3 of these supplements in healthy male athletes for their muscle perfusion-enhancing potential using contrast-enhanced ultrasound (CEUS). METHODS: This placebo-controlled, double-blind, randomized cross-over trial will be carried out at the Center for Orthopedics, Trauma Surgery and Spinal Cord Injury of the University Hospital Heidelberg. Three commercial NO enhancing products including 300 mg of the specific green tea extract VASO6 and a combination of 8 g L-citrulline malate and 3 g L-arginine hydrochloride will be examined for their potential to increase muscular perfusion in 30-male athletes between 18 and 40 years and will be compared with a placebo. On each of the 3 appointments CEUS of the dominant biceps muscle will be performed at rest and after a standardized resistance training. Every athlete receives each of the 3 supplements once after a wash-out period of at least 1 week. Perfusion will be quantified via VueBox quantification software. The results of CEUS perfusion measurements will be compared intra- and interindividually and correlated with clinical parameters. DISCUSSION: The results of this study may help to establish CEUS as a suitable imaging modality for the evaluation of potentially vasodilatory drugs in the field of sports. Other supplements could also be evaluated in this way to verify the content of their advertising claims. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), ID: DRKS00016972, registered on 25.03.2019.


Assuntos
Arginina/administração & dosagem , Citrulina/administração & dosagem , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/diagnóstico por imagem , Chá , Ultrassonografia/métodos , Adolescente , Adulto , Meios de Contraste , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Vasodilatação
3.
J Sports Med Phys Fitness ; 60(8): 1057-1064, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32955831

RESUMO

BACKGROUND: Rock climbers are characterized by enhanced forearm fatigue resistance. This study compared the forearm isometric force of rock climbers (RC), strength-matched power lifters (PL) and aerobically trained (AT) athletes to determine the contribution of muscle oxygen desaturation during ischemia. METHODS: Aerobically trained athletes (N.=6, 23±1 years, 77±1 kg), power lifters (N.=7, 24±1 years, 80±3 kg) and rock climbers (N.=8, 25±2 years, 74±2 kg) took part in a controlled forearm ischemic occlusion (5 min) assessment using near infrared spectroscopy. In addition, three fatigue protocols were completed: protocol 1, sustained maximal voluntary contraction (MVC) until exhaustion; protocol 2, sustained 40% MVC for 3 mins duration; protocol 3, an intermittent 40% MVC (5-s contraction, 5-s recovery) for a duration of 3 mins. Forearm contractile fatigue was quantified as the reduction in MVC. RESULTS: MVC was equivalent between groups (P>0.05). Sustained MVC force (time to decline 50% MVC) was longer in the RC versus AT (AT: 35±5, PL: 46±6, RC: 54±4 s, P<0.05) and both AT and PL for sustained 40% MVC (AT: 56±9, RT: 62±8, RC: 87±7 s, P<0.05). Reduction in MVC was less in RC post intermittent 40% contractions (P<0.05). Oxygen desaturation half-time was longer in the RC versus AT (AT: 65±9, RT: 86±7, RC: 99±7 s, P<0.05) and this was associated with time to 50% MVC (P<0.05, r2=0.53) and time to 40% MVC task failure (P<0.05, r2=0.32). CONCLUSIONS: Rock climbers' enhanced isometric fatigue-resistance and ability to maintain MVC was associated with a lower oxygen consumption of the forearm flexors during the ischemic state. This suggests a training adaptation involving intracellular oxygen consumption.


Assuntos
Antebraço/fisiologia , Montanhismo/fisiologia , Fadiga Muscular/fisiologia , Músculo Esquelético/fisiologia , Adaptação Fisiológica , Adulto , Dedos/fisiologia , Antebraço/irrigação sanguínea , Antebraço/diagnóstico por imagem , Humanos , Contração Isométrica/fisiologia , Masculino , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/diagnóstico por imagem , Consumo de Oxigênio , Condicionamento Físico Humano/fisiologia , Espectroscopia de Luz Próxima ao Infravermelho , Levantamento de Peso/fisiologia , Adulto Jovem
4.
Plast Reconstr Surg ; 146(4): 778-781, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32969999

RESUMO

Mortality after gluteal augmentation with fat transfer techniques is extremely high. Placement of fat subcutaneously versus in the gluteal musculature, or both, is considerably debated. The purpose of this study was to radiographically show the anatomical difference in live subjects in different procedural positions: the flexed or "jackknife" versus prone position. A total of 10 women underwent computed tomographic scanning of the pelvis with venous phase run-off in both the jackknife and prone positions. A computed tomography-specialized radiologist then reviewed images and measured distances from the inferior and superior gluteal veins to the skin and muscle. Three-dimensional imaging and analysis were also performed. Measurements were significantly shorter with respect to distance from skin to muscle, skin to vessel, and vessel to muscle observed from inferior and superior gluteal veins in the jackknife versus the prone position. Three-dimensional modeling showed a significant reduction in the volume and inferior and superior gluteal vein diameters when in the jackknife position. When placed in the jackknife position for gluteal augmentation with fat transfer, extreme caution should be taken with the injecting cannula, as the underlying muscle is only 2 to 3 cm deep. Three-dimensional analysis showed narrowed and reduced volume of gluteal vasculature when in the jackknife position; this is a possible indication of torsion or stretch on the vessel around the pelvic rim that could cause vein avulsion injury from the pressurized fat within the piriform space.


Assuntos
Nádegas/irrigação sanguínea , Nádegas/diagnóstico por imagem , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/diagnóstico por imagem , Posicionamento do Paciente/métodos , Tomografia Computadorizada por Raios X , Adulto , Nádegas/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Músculo Esquelético/cirurgia , Decúbito Ventral , Estudos Prospectivos , Procedimentos Cirúrgicos Reconstrutivos , Adulto Jovem
5.
Arterioscler Thromb Vasc Biol ; 40(10): 2454-2467, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32787524

RESUMO

OBJECTIVE: There has been little success in translating preclinical studies of mouse hind limb ischemia into benefit for patients with peripheral artery disease. Using systematic strategies, we sought to define the injury and angiogenesis landscapes in mice subjected to hind limb ischemia and ascertain whether published studies to date have used an analysis strategy concordant with these data. Approach and Results: Maps of ischemic injury were generated from 22 different hind limb muscles and 33 muscle territories in 12-week-old C57BL/6 mice, based on loss or centralization of myofiber nuclei. Angiogenesis was similarly mapped based on CD (cluster of differentiation) 31-positive capillary content. Only 10 of 33 muscle territories displayed consistent muscle injury, with the distal anterior hind limb muscles most reliably injured. Angiogenesis was patchy and exclusively associated with zones of regenerated muscle (central nuclei). Angiogenesis was not observed in normal appearing muscle, necrotic muscle, or injury border zones. Systematic review of mouse hind limb angiogenesis studies identified 5147 unique publications, of which 509 met eligibility criteria for analysis. Only 7% of these analyzed manuscripts evaluated angiogenesis in distal anterior hind limb muscles and only 15% consistently examined for angiogenesis in zones of muscle regeneration. CONCLUSIONS: In 12-week C57BL/6 mice, angiogenesis postfemoral artery excision proceeds exclusively in zones of muscle regeneration. Only a minority of studies to date have analyzed angiogenesis in regions of demonstrably regenerating muscle or in high-likelihood territories. Quality assurance standards, informed by the atlas and mapping data herein, could augment data reliability and potentially help translate mouse hind limb ischemia studies to patient care.


Assuntos
Isquemia/fisiopatologia , Músculo Esquelético/irrigação sanguínea , Neovascularização Fisiológica , Projetos de Pesquisa/normas , Animais , Confiabilidade dos Dados , Modelos Animais de Doenças , Membro Posterior , Isquemia/patologia , Masculino , Camundongos Endogâmicos C57BL , Desenvolvimento Muscular , Músculo Esquelético/patologia , Necrose , Regeneração , Fluxo Sanguíneo Regional , Fatores de Tempo
6.
Am J Physiol Heart Circ Physiol ; 319(4): H797-H807, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32822215

RESUMO

Patients with type 2 diabetes mellitus (T2DM) exhibit diminished exercise capacity likely attributable to reduced skeletal muscle blood flow (i.e., exercise hyperemia). A potential underlying mechanism of the impaired hyperemic response to exercise could be inadequate blunting of sympathetic-mediated vasoconstriction (i.e., poor functional sympatholysis). Therefore, we studied the hyperemic and vasodilatory responses to handgrip exercise in patients with T2DM as well as vasoconstriction to selective α-agonist infusion. Forearm blood flow (FBF) and vascular conductance (FVC) were examined in patients with T2DM (n = 30) as well as nondiabetic controls (n = 15) with similar age (59 ± 9 vs. 60 ± 9 yr, P = 0.69) and body mass index (31.4 ± 5.2 vs. 29.5 ± 4.6 kg/m2, P = 0.48). Intra-arterial infusion of phenylephrine (α1-agonist) and dexmedetomidine (α2-agonist) were used to induce vasoconstriction: [(FVCwith drug - FVCpredrug)/FVCpredrug × 100%]. Subjects completed rest and dynamic handgrip exercise (20% of maximum) trials per α-agonist. Patients with T2DM had smaller increases (Δ from rest) in FBF (147 ± 71 vs. 199 ± 63 ml/min) and FVC (126 ± 58 vs. 176 ± 50 ml·min-1·100 mmHg-1, P < 0.01 for both) during exercise compared with controls, respectively. During exercise, patients with T2DM had greater α1- (-16.9 ± 5.9 vs. -11.3 ± 3.8%) and α2-mediated vasoconstriction (-23.5 ± 7.1 vs. -19.0 ± 6.5%, P < 0.05 for both) versus controls. The magnitude of sympatholysis (Δ in %vasoconstriction between exercise and rest) for PE was lower (worse) in patients with T2DM versus controls (14.9 ± 12.2 vs. 23.1 ± 8.1%, P < 0.05) whereas groups were similar during DEX trials (24.6 ± 12.3 vs. 27.6 ± 13.4%, P = 0.47). Our data suggest patients with T2DM have attenuated hyperemic and vasodilatory responses to exercise, which could be attributable to greater α1-mediated vasoconstriction in contracting skeletal muscle.NEW & NOTEWORTHY Findings presented in this article are the first to show patients with type 2 diabetes mellitus have blunted hyperemic and vasodilatory responses to dynamic handgrip exercise. Moreover, we illustrate greater α1-adrenergic-mediated vasoconstriction may contribute to our initial observations. Collectively, these data suggest patients with type 2 diabetes may have impaired functional sympatholysis, which can contribute to their reduced exercise capacity.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Diabetes Mellitus Tipo 2/fisiopatologia , Contração Muscular , Músculo Esquelético/irrigação sanguínea , Fenilefrina/administração & dosagem , Vasoconstrição/efeitos dos fármacos , Idoso , Tolerância ao Exercício/efeitos dos fármacos , Feminino , Antebraço , Humanos , Hiperemia/metabolismo , Hiperemia/fisiopatologia , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória
7.
Nat Commun ; 11(1): 3953, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769974

RESUMO

Many important cell types in adult vertebrates have a mesenchymal origin, including fibroblasts and vascular mural cells. Although their biological importance is undisputed, the level of mesenchymal cell heterogeneity within and between organs, while appreciated, has not been analyzed in detail. Here, we compare single-cell transcriptional profiles of fibroblasts and vascular mural cells across four murine muscular organs: heart, skeletal muscle, intestine and bladder. We reveal gene expression signatures that demarcate fibroblasts from mural cells and provide molecular signatures for cell subtype identification. We observe striking inter- and intra-organ heterogeneity amongst the fibroblasts, primarily reflecting differences in the expression of extracellular matrix components. Fibroblast subtypes localize to discrete anatomical positions offering novel predictions about physiological function(s) and regulatory signaling circuits. Our data shed new light on the diversity of poorly defined classes of cells and provide a foundation for improved understanding of their roles in physiological and pathological processes.


Assuntos
Diferenciação Celular , Fibroblastos/fisiologia , Células-Tronco Mesenquimais/fisiologia , Miócitos de Músculo Liso/fisiologia , Pericitos/fisiologia , Animais , Separação Celular , Vasos Coronários/citologia , Matriz Extracelular/metabolismo , Fibroblastos/citologia , Citometria de Fluxo , Intestinos/irrigação sanguínea , Intestinos/citologia , Masculino , Camundongos , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/citologia , Músculo Liso Vascular/citologia , Miocárdio/citologia , Miócitos de Músculo Liso/citologia , Pericitos/citologia , RNA-Seq , Análise de Célula Única , Bexiga Urinária/irrigação sanguínea , Bexiga Urinária/citologia
8.
J Vasc Res ; 57(4): 185-194, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32526735

RESUMO

Information on the function of transient receptor potential vanilloid 1 (TRPV1) in arteriogenesis is limited. We aimed to verify whether TRPV1 is involved in collateral vessel growth in rat hind limbs and elucidate the possible subcellular action mechanisms. Adult Sprague Dawley rats were chosen to establish the hind limb ischemic model and treatment with capsaicin. Angiographies were performed, and tissue was isolated for immunohistochemistry. In vitro, rat aortic endothelial cells (RAECs) were treated with capsaicin and antagonist capsazepine. The RAEC proliferation was determined, and the protein and mRNA levels of Ca2+-dependent transcription factors were assessed. In vivo, the collateral vessels exhibited positive outward remodeling characterized by enhanced inflammatory cell/macrophage accumulation in the adventitia and activated cell proliferation in all layers of the vascular wall and elevated endothelial NO synthetase expression in the rats with hind limb ligation. In RAECs, TRPV1 activation-induced Ca2+-dependent transcriptional factors, nuclear factor of activated T cells 1, calsenilin and myocyte enhancer factor 2C increase, and augmented RAEC proliferation could be a subcellular mechanism for TRPV1 in endothelial cells and ultimately contribute to collateral vessel growth. TRPV1, a novel candidate, positively regulates arteriogenesis, meriting further studies to unravel the potential therapeutic target leading to improved collateral vessel growth for treating ischemic diseases.


Assuntos
Indutores da Angiogênese/farmacologia , Artérias/efeitos dos fármacos , Capsaicina/farmacologia , Circulação Colateral/efeitos dos fármacos , Isquemia/tratamento farmacológico , Músculo Esquelético/irrigação sanguínea , Neovascularização Fisiológica/efeitos dos fármacos , Canais de Cátion TRPV/agonistas , Animais , Artérias/metabolismo , Artérias/fisiopatologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Membro Posterior , Isquemia/metabolismo , Isquemia/fisiopatologia , Proteínas Interatuantes com Canais de Kv/metabolismo , Fatores de Transcrição MEF2/metabolismo , Fatores de Transcrição NFATC/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional , Transdução de Sinais , Canais de Cátion TRPV/metabolismo
9.
Am J Physiol Heart Circ Physiol ; 319(1): H171-H182, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32502377

RESUMO

The role of the ASIC1a in evoking the exercise pressor reflex in rats with simulated peripheral artery disease is unknown. This prompted us to determine whether ASIC1a plays a role in evoking the exaggerated exercise pressor reflex in decerebrated rats with simulated peripheral artery disease. To simulate peripheral artery disease, we ligated the left femoral artery 72 h before the experiment. The right femoral artery was freely perfused and used as a control. To test our hypothesis, we measured the effect of injecting two ASIC1a blockers into the arterial supply of the triceps surae muscles with and without the femoral artery ligated on the reflex pressor responses to 1) static contraction of the triceps surae muscles, 2) calcaneal tendon stretch, and 3) intra-arterial injection of diprotonated phosphate (pH 6.0). We found that the ASIC1a blockers psalmotoxin-1 (200 ng/kg) and mambalgin-1 (6.5 µg/kg) decreased the pressor responses to static contraction as well as the peak pressor responses to injection of diprotonated phosphate when these responses were evoked from the freely perfused hindlimb. In contrast, ASIC1a blockers only decreased the peak pressor responses evoked by injection of diprotonated phosphate in the hindlimb circulation with simulated peripheral artery disease. This inhibitory effect was less than the one measured from the healthy hindlimb. Independently of the hindlimb of interest, ASIC1a blockers had no effect on the pressor responses to tendon stretch. Our results do not support the hypothesis that ASIC1a play a role in evoking the exercise pressor reflex arising from a hindlimb with simulated peripheral artery disease.NEW & NOTEWORTHY The role of ASIC1a in evoking the metabolic component of the exercise pressor reflex in peripheral artery disease is unknown. Using a within-rat experimental design, we found that the contribution of ASIC1a decreased in a rat model of peripheral artery disease. These results have key implications to help finding better treatments and improve morbidity, quality of life, and mortality in patients with peripheral artery disease.


Assuntos
Canais Iônicos Sensíveis a Ácido/metabolismo , Contração Muscular , Doença Arterial Periférica/metabolismo , Esforço Físico , Reflexo , Bloqueadores do Canal Iônico Sensível a Ácido/farmacologia , Animais , Venenos Elapídicos/farmacologia , Artéria Femoral/fisiopatologia , Masculino , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiopatologia , Peptídeos/farmacologia , Doença Arterial Periférica/fisiopatologia , Ratos , Ratos Sprague-Dawley , Venenos de Aranha/farmacologia , Tendões/fisiopatologia
10.
Surgery ; 168(1): 155-159, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32493616

RESUMO

BACKGROUND: Neuropeptide Y acts directly on the vasculature as a cotransmitter with norepinephrine for an augmented contraction. Little, however, is known about the effects of neuropeptide Y on the microvasculature of human skeletal muscle. Neuropeptide Y signaling has not been studied in the setting of cardiac surgery and cardiopulmonary bypass. We investigated the role of neuropeptide Y signaling on vasomotor tone in the microvessels of human skeletal muscle, as well as the effect of cardiopulmonary bypass on neuropeptide Y-induced responsiveness. METHODS: Specimens taken from intercostal muscles were collected from patients, pre- and post-cardiopulmonary bypass, undergoing coronary artery bypass grafting or cardiac valve surgery (n = 8/group). Microvessels (157 ± 47 microns) were isolated in vitro in a no-flow state. Arterial microvascular responses to a neuropeptide Y agonist, a Y1 receptor antagonist, phenylephrine, and the coadministration of neuropeptide Y and phenylephrine were examined. The abundance and localization of the Y1 receptor were measured using Western blot and immunofluorescence, respectively. RESULTS: Arterial microvessels showed responsiveness to the neuropeptide Y agonist (10-9 to 4 × 10-7 mol/L) both before and after cardiopulmonary bypass, reaching a 12.5% vasoconstriction from the baseline luminal diameter. With administration of the Y1 receptor antagonist after neuropeptide Y, the contractile response was eliminated (n = 3/group, P = .04). No difference in vasoconstriction was observed between pre- and post-cardiopulmonary bypass groups (P = .73). The coadministration of neuropeptide Y and phenylephrine (10-9 to 10-4 mol/L) elicited no difference in vasoconstriction (n = 7/group, P = .06 both pre- and post-cardiopulmonary bypass) when compared with phenylephrine alone (10-9 to 10-4 mol/L). No change in the protein expression or localization of the Y1 receptor was detected by Western blotting (n = 6/group, P = .44) or immunofluorescence (n = 6/group, P = .13). CONCLUSION: Neuropeptide Y induced vasoconstriction, suggesting that neuropeptide Y may play an important role in the regulation of the peripheral microvasculature. There was no change in microvascular responsiveness to neuropeptide Y after cardiopulmonary bypass nor were there any synergistic effects of neuropeptide Y on phenylephrine-induced vasoconstriction in the skeletal muscle microvasculature.


Assuntos
Ponte Cardiopulmonar , Microvasos/fisiologia , Neuropeptídeo Y/fisiologia , Vasoconstrição , Idoso , Feminino , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/irrigação sanguínea
11.
Life Sci ; 256: 117989, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32565250

RESUMO

AIMS: The beneficial effects of cannabinoid type 2 receptor (CB2R) activation have been verified in various tissue repair processes. Our recent study revealed CB2R activation promotes myogenesis partly through Nrf2 signaling in a mouse skeletal muscle ischemia-reperfusion (IR) injury model. Other relevant mechanisms need to be further elucidated. Macrophages orchestrate tissue regeneration mainly by changing their phenotype and function. The aim of this study was to investigate the role of CB2R in IR-induced skeletal muscle regeneration, focusing on its impact on macrophage polarization and the consequences on myogenesis. MAIN METHODS: The effects of CB2R on skeletal muscle regeneration, and the macrophage infiltration and M1/M2 polarization were tested with the IR injury model in wild type (WT) and CB2R knockout (CB2R-KO) mice. The effect of CB2R on peritoneal macrophage polarization, and its impact on the myoblasts differentiation was evaluated by co-culture experiments in vitro. KEY FINDINGS: The present study revealed the myofiber regeneration was hindered in the CB2R-KO mice. The infiltration of M1 macrophages and relevant markers' protein expression were enhanced in the CB2R-KO mice, while that of M2 macrophages was decreased compared with the WT mice. The in vitro studies further demonstrated that the absence of CB2R promoted M1 polarization while inhibited M2 polarization. The promoted M1 polarization and retarded M2 polarization in CB2R-KO macrophages hindered myoblasts differentiation. SIGNIFICANCE: Overall, these results suggested CB2R plays a beneficial effect on skeletal muscle regeneration partly by regulating macrophage M1/M2 polarization after IR injury in mice.


Assuntos
Polaridade Celular/fisiologia , Macrófagos/fisiologia , Músculo Esquelético/fisiologia , Receptor CB2 de Canabinoide/deficiência , Regeneração/fisiologia , Traumatismo por Reperfusão/metabolismo , Animais , Células Cultivadas , Técnicas de Cocultura , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Esquelético/irrigação sanguínea
12.
Proc Natl Acad Sci U S A ; 117(25): 14354-14364, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32513697

RESUMO

Ischemic injury initiates a sterile inflammatory response that ultimately participates in the repair and recovery of tissue perfusion. Macrophages are required for perfusion recovery during ischemia, in part because they produce growth factors that aid in vascular remodeling. The input signals governing this pro-revascularization phenotype remain of interest. Here we found that hindlimb ischemia increases levels of resolvin D1 (RvD1), an inflammation-resolving lipid mediator that targets macrophages via its receptor, ALX/FPR2. Exogenous RvD1 enhances perfusion recovery during ischemia, and mice deficient in Alx/Fpr2 have an endogenous defect in this process. Mechanistically, RNA sequencing revealed that RvD1 induces a transcriptional program in macrophages characteristic of a pro-revascularization phenotype. Vascularization of ischemic skeletal muscle, as well as cutaneous wounds, is impaired in mice with myeloid-specific deficiency of Alx/Fpr2, and this is associated with altered expression of pro-revascularization genes in skeletal muscle and macrophages isolated from skeletal muscle. Collectively, these results uncover a role of ALX/FPR2 in revascularization that may be amenable to therapeutic targeting in diseases associated with altered tissue perfusion and repair.


Assuntos
Ácidos Docosa-Hexaenoicos/metabolismo , Isquemia/imunologia , Neovascularização Fisiológica/imunologia , Receptores de Formil Peptídeo/metabolismo , Receptores de Lipoxinas/metabolismo , Cicatrização/imunologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Técnicas de Inativação de Genes , Humanos , Isquemia/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Knockout , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/imunologia , Músculo Esquelético/patologia , Cultura Primária de Células , RNA-Seq , Receptores de Formil Peptídeo/genética , Receptores de Lipoxinas/genética , Transdução de Sinais/imunologia , Pele/irrigação sanguínea , Pele/imunologia , Pele/lesões , Pele/patologia , Transcrição Genética/imunologia
13.
Medicine (Baltimore) ; 99(24): e20310, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541454

RESUMO

RATIONALE: Mitochondrial encephalomyopathy with lactic acidosis and stroke- like episodes (MELAS) syndrome is caused by mitochondrial respiratory chain dysfunction and oxidative phosphorylation disorder. It is a rare clinical metabolic disease involved with multiple systems. PATIENT CONCERNS: A 22-year-old patient presented with limb convulsion accompanied by loss of consciousness, headache, partial blindness, blurred vision, and so on. DIAGNOSES: Brain magnetic resonance imaging showed a high-intensity area in bilateral occipital cortex, left parietal lobe and cerebellum on diffusion-weighted imaging. These focus did not distribute as vascular territory. The pathological examination of skeletal muscle revealed several succinate dehydrogenase reactive vessels with overreaction and increased content of lipid droplets in some muscle fibers. Genetic testing showed that the patient carried m.10158T>C mutation. INTERVENTIONS: She was provided with traditional arginine hydrochloride therapy and orally medication of coenzyme Q (10 mg). OUTCOMES: Mitochondrial DNA of blood and hair follicle of patient carried m.10158T>C mutation LESSONS:: For the suspected patients of MELAS syndrome, if the hot-spot mutation test is negative, more detection sites should be selected.


Assuntos
Acidose Láctica/complicações , DNA Mitocondrial/genética , Síndrome MELAS/genética , Acidente Vascular Cerebral/etiologia , Administração Oral , Arginina/administração & dosagem , Arginina/uso terapêutico , Conscientização , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Feminino , Humanos , Síndrome MELAS/diagnóstico por imagem , Síndrome MELAS/tratamento farmacológico , Síndrome MELAS/patologia , Imagem por Ressonância Magnética/métodos , Micronutrientes/administração & dosagem , Micronutrientes/uso terapêutico , Encefalomiopatias Mitocondriais/diagnóstico , Encefalomiopatias Mitocondriais/etiologia , Encefalomiopatias Mitocondriais/patologia , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Mutação , Acidente Vascular Cerebral/diagnóstico , Succinato Desidrogenase/metabolismo , Ubiquinona/administração & dosagem , Ubiquinona/uso terapêutico , Adulto Jovem
14.
J Frailty Aging ; 9(3): 134-138, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32588026

RESUMO

BACKGROUND: High levels of intramuscular adipose tissue and low levels of capillarization are both predicative of low muscle and mobility function in older adults, however little is known about their relationship. OBJECTIVES: The purpose of this study was to examine the relationship of intramuscular adipose tissue and capillarization in older adults. SETTING: An outpatient medical center. PARTICIPANTS: Forty-seven sedentary adults (age 59.9 ± 1.0 years, BMI 32.0 ± 0.7 kg/m2, VO2max 22.4 ± 0.7 ml/kg/min); Measurements: All participants underwent CT scans to determine intramuscular adipose tissue and muscle biopsies to determine capillarization in the mid-thigh. A step-wise hierarchical linear regression analysis was used to examine the contributions of age, sex, race, body mass index, 2-hour postprandial glucose, VO2max, and muscle capillarization, to the variability in intramuscular adipose tissue. RESULTS: The predictors as a group accounted for 38.1% of the variance in intramuscular adipose tissue, with body mass index and capillarization each significantly contributing to the final model (P<0.001). The part correlation of body mass index with intramuscular adipose tissue was r = 0.47, and the part correlation of capillarization with intramuscular adipose tissue was r = 0.39, indicating that body mass index and capillarization explained 22.1%, and 15.2% of the variance in intramuscular adipose tissue. CONCLUSIONS: While increased muscle capillarization is typically thought of as a positive development, in some clinical conditions, such as tendinopathies, an increase in capillarization is part of the pathological process related to expansion of the extracellular matrix and fibrosis. This may also be an explanation for the surprising finding that high capillarization is related to high levels of intramuscular adipose tissue. Future studies are necessary to determine the relationship of changes in both capillarization and intramuscular adipose tissue after interventions, such as exercise.


Assuntos
Tecido Adiposo/metabolismo , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/metabolismo , Índice de Massa Corporal , Capilares/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Coxa da Perna/irrigação sanguínea
15.
Artigo em Inglês | MEDLINE | ID: mdl-32466396

RESUMO

Background: The aim of the present study was to evaluate the effects of post-activation performance enhancement (PAPE) during successive sets of the bench press (BP) exercise under blood flow restriction (BFR). Methods: The study included 10 strength-trained males (age = 29.8 ± 4.6 years; body mass = 94.3 ± 3.6 kg; BP 1-repetition maximum (1RM) = 168.5 ± 26.4 kg). The experiment was performed following a randomized crossover design, where each participant performed two different exercise protocols: under blood flow restriction (BFR) and control test protocol (CONT) without blood flow restriction. During the experimental sessions, the study participants performed 3 sets of 3 repetitions of the BP exercise at 70%1RM with a 5 min rest interval between sets. The differences in peak power output (PP), mean power output (MP), peak bar velocity (PV), and mean bar velocity (MV) between the CONT and BFR conditions were examined using 2-way (condition × set) repeated measures ANOVA. Furthermore, t-test comparisons between conditions were made for the set 2-set 1, set 3-set 1, and set 3-set 2 delta values for all variables. Results: The post hoc results for condition × set interaction in PP showed a significant increase in set 2 compared to set 1 for BFR (p < 0.01) and CONT (p = 0.01) conditions, a significant increase in set 3 compared to set 1 for the CONT (p = 0.01) condition, as well as a significant decrease in set 3 compared to set 1 for BFR condition occurred (p < 0.01). The post hoc results for condition × set interaction in PV showed a significant increase in set 2 compared to set 1 for BFR (p < 0.01) and CONT (p = 0.01) conditions, a significant increase in set 3 compared to set 1 for CONT (p = 0.03) condition, as well as a significant decrease in set 3 compared to set 1 for BFR condition (p < 0.01). The t-test comparisons showed significant differences in PP (p < 0.01) and PV (p = 0.01) for set 3-set 2 delta values between BFR and CONT conditions. Conclusion: The PAPE effect was analyzed through changes in power output and bar velocity that occurred under both the CONT and BFR conditions. However, the effects of PAPE have different kinetics in successive sets for BFR and for CONT conditions.


Assuntos
Exercício Físico , Hemodinâmica , Músculo Esquelético , Treinamento de Resistência , Adulto , Humanos , Masculino , Músculo Esquelético/irrigação sanguínea , Fluxo Sanguíneo Regional
16.
Arterioscler Thromb Vasc Biol ; 40(7): 1695-1704, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32404008

RESUMO

OBJECTIVE: In mice fed a high-fat diet, impairment of insulin signaling in endothelium is an early phenomenon that precedes decreased insulin sensitivity of skeletal muscle, adipose tissue, and liver. We assessed in humans whether short-term overfeeding affects insulin-induced microvascular recruitment in skeletal muscle and adipose tissue before changes occur in glucose uptake and lipolysis. Approach and Results: Fifteen healthy males underwent a hypercaloric and subsequent hypocaloric diet intervention. Before, during, and after the hypercaloric diet, and upon return to baseline weight, all participants underwent (1) a hyperinsulinemic-euglycemic clamp to determine insulin-induced glucose uptake and suppression of lipolysis (2) contrast-enhanced ultrasonography to measure insulin-induced microvascular recruitment in skeletal muscle and adipose tissue. In addition, we assessed insulin-induced vasodilation of isolated skeletal muscle resistance arteries by pressure myography after the hypercaloric diet in study participants and controls (n=5). The hypercaloric diet increased body weight (3.5 kg; P<0.001) and fat percentage (3.5%; P<0.001) but did not affect glucose uptake nor lipolysis. The hypercaloric diet increased adipose tissue microvascular recruitment (P=0.041) and decreased the ratio between skeletal muscle and adipose tissue microvascular blood volume during hyperinsulinemia (P=0.019). Insulin-induced vasodilation of isolated skeletal muscle arterioles was significantly lower in participants compared with controls (P<0.001). The hypocaloric diet reversed all of these changes, except the increase in adipose tissue microvascular recruitment. CONCLUSIONS: In lean men, short-term overfeeding reduces insulin-induced vasodilation of skeletal muscle resistance arteries and shifts the distribution of tissue perfusion during hyperinsulinemia from skeletal muscle to adipose tissue without affecting glucose uptake and lipolysis. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02628301.


Assuntos
Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/metabolismo , Arteríolas/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Restrição Calórica , Ingestão de Energia , Insulina/administração & dosagem , Lipólise/efeitos dos fármacos , Microcirculação/efeitos dos fármacos , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/metabolismo , Adiposidade , Adolescente , Adulto , Arteríolas/fisiologia , Glicemia/metabolismo , Estudos de Casos e Controles , Voluntários Saudáveis , Humanos , Resistência à Insulina , Masculino , Fatores de Tempo , Vasodilatação/efeitos dos fármacos , Ganho de Peso , Perda de Peso , Adulto Jovem
17.
Otolaryngol Head Neck Surg ; 162(6): 993-995, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32393106

RESUMO

We describe the use of the medial sural artery musculocutaneous perforator (MSAP) flap at our institution. It is a relatively new flap, originally described in 2001 for lower extremity defects, that has become increasingly popular for head and neck reconstruction due to its versatility, thinness, pliability, long pedicle, and particularly favorable donor site. It has been described for reconstruction of oral defects, but there is little published on its use in pharyngeal reconstruction. We suggest that the MSAP is an ideal flap for addressing defects caused by pharyngoesophageal stenosis, pharyngeal fistulas, or laryngopharyngectomies. We review 5 cases at our institution from June 2016 to November 2017.


Assuntos
Artérias/transplante , Esôfago/cirurgia , Músculo Esquelético/transplante , Retalho Perfurante/irrigação sanguínea , Faringe/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Transplante de Pele/métodos , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/irrigação sanguínea , Estudos Retrospectivos
18.
Scand J Med Sci Sports ; 30(7): 1117-1131, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32246511

RESUMO

Angiogenic, mitochondrial, and related transcriptional proteins were assessed in human skeletal muscle and isolated vascular cells during the early phase of endurance training. Thigh muscle biopsies were obtained in healthy young subjects, after one acute bout (n = 9) and after 3, 5, 7, and 14 days (n = 9) of cycle ergometer training. Whole muscle homogenates were analyzed for angiogenic, mitochondrial, and regulatory mRNA and protein levels. Angiogenic proteins were determined in muscle-derived endothelial cells and pericytes sorted by fluorescence-activated cell sorting. Acute exercise induced an increase in whole muscle mRNA of peroxisome proliferator-activated receptor gamma coactivator 1α (4.5-fold; P = .002) and vascular endothelial growth factor (VEGF) (2.4-fold; P = .001) at 2 hours post. After 14 days of training, there was an increase in CD31 protein (63%; P = .010) in whole muscle indicating capillary growth. There was also an increase in muscle VEGF receptor 2 (VEGFR2) (1.5-fold; P = .013), in OXPHOS proteins (complex I, II, IV, V; 1.4- to 1.9-fold; P < .05) after 14 days of training and an increase in estrogen-related receptorα protein (1.5-fold; P = .039) at 14 days compared to 5 days of training. Both endothelial cells and pericytes expressed VEGF and other angiogenic factors at the protein level but with a distinctively lower expression of VEGFR2 and thrombospondin-1 (TSP-1) in pericytes. The findings illustrate that initiation of capillary and mitochondrial adaptations occurs within 14 days of training and suggest that sustained changes in angiogenic proteins including VEGF and TSP-1 are moderate in whole muscle and vascular cells.


Assuntos
Proteínas Angiogênicas/metabolismo , Treino Aeróbico , Proteínas Mitocondriais/metabolismo , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/metabolismo , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Neovascularização Fisiológica , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Adulto Jovem
20.
Sci Rep ; 10(1): 6342, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286372

RESUMO

Impairments in oxygen delivery and consumption can lead to reduced muscle endurance and physical disability. Perfusion, a measure of microvascular blood flow, provides information on nutrient delivery. T2* provides information about relative tissue oxygenation. Changes in these parameters following stress, such as exercise, can yield important information about imbalance between delivery and consumption. In this study, we implemented novel golden angle radial MRI acquisition technique to simultaneously quantify muscle perfusion and T2* at 7T with improved temporal resolution, and demonstrated assessment of spatial and temporal changes in these parameters within calf muscles during recovery from plantar flexion exercise. Nine healthy subjects participated the studies. At rest, perfusion and T2* in gastrocnemius muscle group within calf muscle were 5 ± 2 mL/100 g/min and 21.1 ± 3 ms respectively. Then the subjects performed plantar flexion exercise producing a torque of ~8ft-lb. Immediately after the exercise, perfusion was elevated to 79.3 ± 9 mL/100 g/min and T2* was decreased by 6 ± 3%. The time constants for 50% perfusion and T2* recovery were 54.1 ± 10 s and 68.5 ± 7 s respectively. These results demonstrate successful simultaneous quantification of perfusion and T2* in skeletal muscle using the developed technique.


Assuntos
Exercício Físico , Músculo Esquelético/fisiologia , Consumo de Oxigênio , Fluxo Sanguíneo Regional , Adolescente , Adulto , Feminino , Humanos , Perna (Membro)/fisiologia , Imagem por Ressonância Magnética , Masculino , Contração Muscular , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/diagnóstico por imagem
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