Tissue desaturation is not a major determinant of aging-related impairment in skeletal muscle reactive hyperemia: a retrospective analysis.

Near-infrared spectroscopy combined with vascular occlusion test (NIRS-VOT) is a reactive hyperemia technique for in vivo evaluation of skeletal muscle microvascular reactivity. Previous studies using NIRS-VOT have been shown to be able to detect impairments in microvascular function in high-risk cardiovascular disease populations, such as older individuals. It has been demonstrated that older individuals have slower reactive hyperemia compared with young individuals. Importantly, older individuals also show less desaturation during ischemia compared with young individuals. Based on these findings, it has been suggested that the slower reactive hyperemia observed in older individuals is explained by the lower desaturation during blood flow occlusion (reduced ischemic stimulus). This retrospective analysis compared reactive hyperemia in 36 young and 47 older tissue desaturation-matched individuals that underwent 5-min blood flow occlusion. Overall, we showed that older individuals have impaired reactive hyperemia compared with young when matching for the degree of desaturation and blood flow occlusion time. These findings provide evidence that lower tissue desaturation during ischemia is not a major determinant of impaired reactive hyperemia in older individuals.NEW & NOTEWORTHY Previous findings have suggested that aging-related impairment in skeletal muscle reactive hyperemia is majorly influenced by a lower degree of tissue desaturation during ischemia in older individuals compared with young individuals. In a retrospective analysis including 83 tissue desaturation-matched individuals, we show that the degree of tissue desaturation is not a major determinant of aging-related impairments in reactive hyperemia.

The Effect of Social Determinants of Health in Treating Chronic Limb-Threatening Ischemia.

Social determinants of health (SDOHs) are broadly defined as nonmedical factors that impact the outcomes of one's health. SDOHs have been increasingly recognized in the literature as profound and modifiable factors on the outcomes of vascular care in peripheral artery disease (PAD) and chronic limb-threatening ischemia (CLTI) despite surgical and technological advancements. In this paper, we briefly review the SDOH and its impact on the management and outcome of patients with CLTI. We highlight the importance of understanding how SDOH impacts our patient population so the vascular community may provide more effective, inclusive, and equitable care.

Regenerative effect of platelet-rich plasma in the murine ischemic limbs.

AIMS: The purpose of this study was to investigate the effect of PPRP (pure PRP) and LPRP (PRP with leukocytes) on recovery from limb ischemia and on expression of growth factors involved in angiogenesis, myogenesis and fibrogenesis. MATERIAL AND METHODS: PPRP and LPRP prepared by centrifugation were added to cultures of C2C12 and NIH3T3 cells (1 or 10% PRPs) to evaluate alterations in cell metabolism and expression of growth factors by MTT, ELISA and RT-qPCR, respectively. To evaluate in vivo regenerative effects, PRPs were injected into the ischemic limbs of BALB/c mice and muscle mass/strength and histomorphometry were evaluated after 30 days. KEY FINDINGS: Mice treated with PRPs after limb ischemia showed an increase in the size of myofibers and muscle strength, reduced fibrosis and adipocytes, and decreased capillary density and necrosis scores compared to untreated mice. In cell culture, serum deprivation reduced the viability of C2C12 and NIH3T3 cells to about 50%, but the addition of 1% PRPs completely recovered this loss. Both PRPs, downregulated most of the tested genes; however, angiogenic gene Vegfa in C2C12 and the fibrogenic genes Col1a1 and Col3a1 in NIH3T3 cells were upregulated by LPRP. SIGNIFICANCE: PPRP and LPRP had similar effects in regulation of genes involved in angiogenesis, myogenesis and fibrogenesis. However, the presence of leucocytes did not significantly affect regenerative activities of PRP in the ischemic limb.

Veno-Occlusive Priapism in COVID-19 Disease.

Infection by COVID-19, being a respiratory disease caused by SARS-CoV-2, can predispose to arterial and venous thrombotic disease, in response to excessive inflammation, platelet activation, endothelial dysfunction, and venous stasis. During the COVID-19 pandemic period, the technological and resource availability for the care of these patients with thrombotic disease is critical, marking a factor of morbidity and poor prognosis in these cases. We describe a case of priapism in a patient with COVID-19, during the course of systemic inflammatory response syndrome and respiratory distress syndrome with a procoagulant state, seeking to relate the pathophysiological factors of ischemic priapism in patients with infection with SARS-Cov-2.

Effects of induced local ischemia during a 4-km cycling time trial on neuromuscular fatigue development.

The present study analyzed the effects of local ischemia during endurance exercise on neuromuscular fatigue (NMF). Nine cyclists performed, in a counterbalanced order, two separate 4-km cycling time trials (TT) with (ISCH) or without (CONTR) induced local ischemia. NMF was characterized by using isometric maximal voluntary contractions (IMVC), whereas central [voluntary activation (VA)] and peripheral fatigue [peak torque of potentiated twitch (TwPt)] of knee extensors were evaluated using electrically evoked contractions performed before (PRE) and 1 min after (POST) the TT. Electromyographic activity (EMG), power output (PO), oxygen uptake (V̇o2), and rating of perceived exertion (RPE) were also recorded. The decrease in IMVC (-15 ± 9% vs. -10 ± 8%, P = 0.66), VA (-4 ± 3% vs. -3 ± 3%, P = 0.46), and TwPt (-16 ± 7% vs. -19 ± 14%, P = 0.67) was similar in ISCH and CONTR. Endurance performance was drastically reduced in ISCH condition (512 ± 29 s) compared with CONTR (386 ± 17 s) (P < 0.001), which was accompanied by lower EMG, PO, and V̇o2 responses (all P < 0.05). RPE was greater in ISCH compared with CONTR (P < 0.05), but the rate of change was similar throughout the TT (8.19 ± 2.59 vs. 7.81 ± 2.01 RPE.% of total time-1, P > 0.05). These results indicate that similar end-exercise NMF levels were accompanied by impaired endurance performance in ISCH compared with CONTR. These novel findings suggest that the local reduced oxygen availability affected the afferent feedback signals to the central nervous system, ultimately increasing perceived effort and reducing muscle activity and exercise intensity to avoid surpassing a sensory tolerance limit before the finish line.

Resistance training with blood flow restriction and cognition in elderly women (project "forte-mente-ativa"): study protocol

Abstract Aim: In the process of aging, there is a decrease on muscle strength and cognitive function. Resistance training combined with blood flow restriction (BFRRT) has been shown capable of maintaining or improve aspects of physical health. However, the effects of BFRRT the cognitive function of the elderly are not clear. This study aimed to describe the design of a randomized controlled clinical trial, that will investigate the effects of BFRRT on cognitive function, physical performance and physiological and morphological aspects in elderly women. Methods: Forty participants will be randomized into one of the following groups: low load resistance training, blood flow restriction resistance training, moderate load resistance training or Control. All intervention groups will complete 16 weeks of resistance training, three times week (45 minutes each), with training consisting of four exercises for the upper and lower body, including three sets of ten repetitions each. No exercise will be performed by the Control group. Cognitive function will be the primary outcome of the study. Secondary outcomes will include body composition, muscle strength, functional capacity, double-task, level of physical activity, static and dynamic balance, brain activity, BDNF neurotrophic factor, anxiety, depression and sleep state). Conclusion: This project will contribute to the existing knowledge and will have a social impact regarding the use of physical exercise as a non-pharmacological tool for the mental and physical health older individuals. Trial Registration: Brazilian Registry of Clinical Trials number RBR-7BC8ZP.

Remodelado cardíaco en el modelo preclínico de falla cardíaca isquémica experimental por dislipidemia en el ratón SR-B1 KO/ApoER6 1h/h / Cardiac remodeling in experimental cardiac failure induced by hyperlipidemia in mice

INTRODUCCIÓN: Los ratones SR-B1 KO/ApoER6 1h/h que son alimentados con una dieta rica en grasas saturadas, desarrollan enfermedad coronaria aterosclerótica severa, complicaciones isquémicas e insuficiencia cardíaca, con alta mortalidad. Los estudios con este modelo se han enfocado fundamentalmente en la enfermedad coronaria y menos en el remodelado cardíaco. El OBJETIVO del trabajo ha sido caracterizar el remodelado miocárdico, evaluar la evolución temporal de la función ventricular izquierda y la sobrevida asociada a enfermedad cardíaca por ateromatosis. MÉTODO: Ratones homocigotos SR-B1 KO/ApoER6 1h/h fueron alimentados por 8 semanas con dieta aterogénica o dieta normal y se comparó la sobrevida en ambos grupos. A las 4 semanas se realizó un ecocardiograma bidimensional. En los ratones eutanasiados se evaluó en la pared cardíaca fibrosis miocárdica y tamaño de los cardiomiocitos por morfometría, apoptosis con técnica de TUNEL e infiltración por células inflamatorias mononucleares (ED1) por inmunohistoquímica. RESULTADOS: En el grupo que recibió dieta aterogénica la sobrevida se redujo en 46,7% (p < 0.001), debido a muerte súbita y a falla cardíaca progresiva. En este grupo, a las 4 semanas se observó dilatación de cavidades izquierdas y disminución de la fracción de eyección del ventrículo izquierdo en comparación con el grupo control (79,3 ± 1,3% vs 66 ± 3,7%, p<0,01). También se observó aumento de la masa cardíaca relativa de 2.1 veces (p<0,001) y del peso pulmonar relativo en 80% (p<0,001), sin cambios en las dimensiones de los cardiomiocitos. En el miocardio de los ratones que recibieron dieta aterogénica hubo un aumento de la fibrosis cardíaca de 7.9 veces (p < 0.01) y del número de cardiomiocitos apoptóticos en 55.9 veces (p < 0.01), junto a un aumento del número de células inflamatorias mononucleares ED1. CONCLUSIONES: En el modelo de falla cardíaca severa de etiología isquémica con alta mortalidad en el ratón homocigoto SR-B1 KO/ApoER6 1h/h sometido a una dieta aterogénica, con falla cardíaca izquierda por disfunción sistólica, el remodelado patológico del miocardio está dado fundamentalmente por apoptosis y fibrosis. También se observa un aumento discreto de macrófagos en la pared cardíaca. Es posible que el edema parietal también pueda ser un mecanismo de remodelado relevante en este modelo.

Abstract: SR-B1 KO/ApoER6 1h/h mice fed a high saturated fat diet develop severe coronary atheromatosis, and cardiac failure with a high mortality rate. Cardiac remodeling under these conditions has not been well studied. AIM: To evaluate the time course of left ventricular function, cardiac remodeling and survival associated to the administration of an atherogenic diet. METHOD: Homozygote SR-B1 KO/ApoER6 1h/h mice received an atherogenic diet for 8 weeks. Mice receiving a normal diet served as controls. Survival rate, myocardial fibrosis, cardiomyocyte size, apoptosis and infiltration by inflammatory or mononuclear cells were compared between groups. A TUNEL technique was used to evaluate apoptosis. RESULTS: A 46.7% survival reduction compared to controls was observed in the experimental group (p<0.01), due to left ventricular and atrial dilatation associated to a decrease in ejection fraction (79,3 ± 1,3% vs 66 ± 3,7%, p<0,01, respectively). Also, an increased cardiac weight, 2.6 times greater was observed in the experimental group, compared to controls. Mice receiving the atherogenic diet showed an 80% increased lung weight. There was no evident change in cardiomyocytes, but there was more (7.9 times) cardiac fibrosis (p<0.01) and 55.9 times more apoptotic cells. (p<0.01), along with a greater number of inflammatory cells and ED1 mononuclear cells. CONCLUSION: Mice receiving an atherogenic diet develop heart failure and reduced survival rate. This is associated with cardiac remodeling with underlying apoptosis an ventricular wall fibrosis. It is posible that wall edema might contribute to the observed cardiac remodeling.

Afferent innervation of the ischemic kidney contributes to renal dysfunction in renovascular hypertensive rats.

The ablation of renal nerves, by destroying both the sympathetic and afferent fibers, has been shown to be effective in lowering blood pressure in resistant hypertensive patients. However, experimental studies have reported that the removal of sympathetic fibers may lead to side effects, such as the impairment of compensatory cardiorenal responses during a hemodynamic challenge. In the present study, we evaluated the effects of the selective removal of renal afferent fibers on arterial hypertension, renal sympathetic nerve activity, and renal changes in a model of renovascular hypertension. After 4 weeks of clipping the left renal artery, afferent renal denervation (ARD) was performed by exposing the left renal nerve to a 33 mM capsaicin solution for 15 min. After 2 weeks of ARD, we found reduced MAP (~ 18%) and sympathoexcitation to both the ischemic and contralateral kidneys in the hypertensive group. Moreover, a reduction in reactive oxygen species was observed in the ischemic (76%) and contralateral (27%) kidneys in the 2K1C group. In addition, ARD normalized renal function markers and proteinuria and podocin in the contralateral kidney. Taken altogether, we show that the selective removal of afferent fibers is an effective method to reduce MAP and improve renal changes without compromising the function of renal sympathetic fibers in the 2K1C model. Renal afferent nerves may be a new target in neurogenic hypertension and renal dysfunction.

Dissection of the Hepatic Artery: A Rare Cause of Late Ischemia After Liver Transplant.

Hepatic artery dissection is an infrequent vascular complication that can arise after orthotopic liver transplant. Most patients with this complication are diagnosed during the intraoperative period or the first days after liver transplant, with an association shown with living-donor liver transplant. In this study, we discuss a rare case of an extrahepatic artery dissection that was successfully managed through surgical excision and arterial revascularization that was diagnosed 4 years after orthotopic liver transplant. Furthermore, we hypothesize on the potential causes of its occurrence.

Analysis of the Safety and Efficacy of the Endovascular Treatment for Acute Limb Ischemia with Percutaneous Pharmacomechanical Thrombectomy Compared with Catheter-Directed Thrombolysis.

BACKGROUND: To evaluate the rates of limb salvage, survival, and perioperative mortality in patients with acute limb ischemia (ALI) submitted to endovascular revascularization with pharmacomechanical thrombectomy (PMT) and catheter-directed thrombolysis (CDT). METHODS: This was a retrospective consecutive cohort study of patients with ALI who were submitted to endovascular treatment with PMT or fibrinolysis at the Division of Vascular and Endovascular Surgery, Hospital do Servidor Público Estadual (São Paulo, Brazil), between July 2015 and December 2018. The limb salvage rate and survival rate at 720 days were analyzed in both the PMT (group 1) and CDT treatment (group 2), as well as the perioperative mortality rate (PMR) at 30 days after surgery. RESULTS: One hundred twelve patients were admitted to the emergency department with ALI between July 2015 and December 2018. Seventeen patients diagnosed with Rutherford III irreversible ALI and 46 patients submitted to open surgery were excluded. Thus, 49 patients were submitted to endovascular surgery; 18 (36.7%) were classified into group 1, and 31 (63.3%) were classified into group 2. The clinical data were equal between the 2 groups, but there was a higher prevalence of thrombophilia in group 1 (3 cases; P < 0.001). The limb salvage rate and the overall survival rate at 720 days were similar between groups 1 and 2 (87.8% vs. 89.7%, P = 0.78 and 84.7% vs. 69.2%, P = 0.82, respectively). There was no statistical difference regarding secondary patency rates at 720 days between groups 1 and 2 (group 1, 81.9% and group 2, 78.8%; P = 0.66). The PMR was 16.7% (8 patients) within the first 30 days. Group 2 had a higher overall mortality rate (OMR) (6 patients, 19.3%, P = 0.03). Regarding the PMT group, there was a higher rate of complications such as myoglobinuria, hematuria, acute renal failure, and death in the subgroup of patients in whom there were performed more than 150 cycles/sec during the surgery (P < 0.001). CONCLUSIONS: In the present study, the PMT and CDT endovascular procedures had similar limb salvage, overall survival, and secondary patency rates. However, the OMR was higher in the CDT group. Another important finding was related to the number of cycles/sec performed in the PMT group, in whom patients with more than 150 cycles/sec have presented with higher rates of hematuria, myoglobinuria, acute renal failure, and death.

Is flow-mediated dilatation associated with near-infrared spectroscopy-derived magnitude of muscle O2 desaturation in healthy young and individuals at risk for cardiovascular disease?

Vascular occlusion test (VOT)-induced reactive hyperemia in brachial artery is crucial to flow-mediated dilation (FMD). Emerging studies have suggested that reactive hyperemia depends on the magnitude of the O2 desaturation (ischemia) in downstream microvessels. Although near-infrared spectroscopy-derived tissue O2 saturation index (TSI) has been used to assess the magnitude of ischemia, the association between FMD and the magnitude of O2 desaturation has not been addressed. Therefore, the aim of the present study was to evaluate whether FMD correlates with the magnitude of muscle O2 desaturation in healthy young individuals and older adults at risk for cardiovascular disease (CVD). Twenty healthy young individuals and 20 others at risk for CVD participated in the study. The magnitude of ischemic stimulus was determined by calculating the area under curve of TSI signal over 5 min of cuff occlusion period. Oxygen resaturation rate was calculated as the upslope of the TSI signal over 10 s following cuff deflation. There was no significant correlation between FMD and the magnitude of ischemic stimulus in both groups assessed (young: R = 0.327; P = 0.159 and older: R = -0.184; P = 0.436). However, a significant correlation between the magnitude of O2 desaturation and O2 resaturation rate in young (R = 0.555; P = 0.011) and older individuals at risk for CVD (R = 0.539; P = 0.014). In conclusion, FMD response did not correlate with the magnitude of muscle O2 desaturation, although it seems to be partially associated with O2 resaturation rate.

Cirugía de hombro en posición silla de playa: estrategias y recomendaciones para la prevención de complicaciones isquémicas / Strategies and recommendations for the prevention of ischemic complications in beach chair position for shoulder surgery

Beach chair position is require for Shoulder surgery frequently for proper resolution. The stroke associated with shoulder surgery is a rare complication and probably underreported. The objective of this article is to review the pathophysiology of the ischemic damage associated with beach chair position, learn about strategies and develop recommendations to minimize risks.

La cirugía de hombro (CH), requiere y requerirá colocar a los pacientes en la posición en silla de playa (PSP), cada vez con mayor frecuencia para su adecuada resolución. El asociado a CH, es una complicación poco frecuente y probablmente subreportada. El objetivo de esta revisión, es repasar la fisiopatología del daño isquémico asociado a PSP, conocer estrategias y elaborar recomedaciones destinadas a minimizar riesgos.

TLR7 mediates increased vulnerability to ischemic acute kidney injury in diabetes.

OBJECTIVE: Diabetes is a risk factor for acute kidney injury (AKI). However, its mechanism of pathogenesis has not been elucidated. The aim of the study was to investigate the role of inflammation and the toll-like receptor 7 (TLR7) in ischemic AKI for diabetes. METHODS: A high glucose hypoxia-reoxygenation model of human renal tubular epithelial (HK-2) cells was used to generate AKI induced by ischemia-reperfusion in diabetes. The activity of cells was measured by CCK-8 assay and LDH activity. Inflammatory cytokines were assessed by ELISA. TLR7, MyD88, and NF-κB expressions were examined by western blotting. Apoptosis was evaluated by flow cytometry. RESULTS: The high glucose group and low glucose group were subjected to hypoxia-reoxygenation. The low glucose group developed only mild cell damage, apoptosis, and inflammatory response. In contrast, an equivalent hypoxia-reoxygenation injury provoked severe cell damage, apoptosis, and inflammatory response in the high glucose group. Expression of TLR7 and its related proteins were measured in the high glucose group before and after hypoxia-reoxygenation. The high glucose group exhibited more significant increases in TLR7 expression following hypoxia-reoxygenation than the low glucose group. In addition, the expression of TLR7 and its related proteins after hypoxia-reoxygenation were higher in the high glucose group than in the low glucose group. Inhibition of TLR7 provides significant protection against ischemic injury in diabetes. CONCLUSION: Our results suggest that diabetes increases the vulnerability to ischemia-induced renal injury. This increased vulnerability originates from a heightened inflammatory response involving the TLR7 signal transduction pathway.

TLR7 mediates increased vulnerability to ischemic acute kidney injury in diabetes

SUMMARY OBJECTIVE Diabetes is a risk factor for acute kidney injury (AKI). However, its mechanism of pathogenesis has not been elucidated. The aim of the study was to investigate the role of inflammation and the toll-like receptor 7 (TLR7) in ischemic AKI for diabetes. METHODS A high glucose hypoxia-reoxygenation model of human renal tubular epithelial (HK-2) cells was used to generate AKI induced by ischemia-reperfusion in diabetes. The activity of cells was measured by CCK-8 assay and LDH activity. Inflammatory cytokines were assessed by ELISA. TLR7, MyD88, and NF-κB expressions were examined by western blotting. Apoptosis was evaluated by flow cytometry. RESULTS The high glucose group and low glucose group were subjected to hypoxia-reoxygenation. The low glucose group developed only mild cell damage, apoptosis, and inflammatory response. In contrast, an equivalent hypoxia-reoxygenation injury provoked severe cell damage, apoptosis, and inflammatory response in the high glucose group. Expression of TLR7 and its related proteins were measured in the high glucose group before and after hypoxia-reoxygenation. The high glucose group exhibited more significant increases in TLR7 expression following hypoxia-reoxygenation than the low glucose group. In addition, the expression of TLR7 and its related proteins after hypoxia-reoxygenation were higher in the high glucose group than in the low glucose group. Inhibition of TLR7 provides significant protection against ischemic injury in diabetes. CONCLUSION Our results suggest that diabetes increases the vulnerability to ischemia-induced renal injury. This increased vulnerability originates from a heightened inflammatory response involving the TLR7 signal transduction pathway.

RESUMO OBJETIVO O diabetes é um fator de risco para a lesão renal aguda (LRA). No entanto, seu mecanismo de patogênese não foi elucidado. O objetivo do estudo foi investigar o papel da inflamação e do receptor Toll-like 7 (TLR7) na LRA isquêmica no diabetes. MÉTODOS Um modelo de hipóxia-reoxigenação de células epiteliais tubulares renais humanas (HK-2) na presença de concentrações altas de glicose foi utilizado para gerar LRA induzida por isquemia-reperfusão em diabetes. A atividade das células foi medida pelo ensaio Cell Counting Kit-8 (CCK-8) e pela atividade da lactato desidrogenase (LDH). As citocinas inflamatórias foram avaliadas por ensaio imunoenzimático (Elisa). A expressão de TLR7, do fator de diferenciação mieloide 88 (MyD88) e do fator de transcrição nuclear-κB (NF-κB) foi examinada por Western blotting. A apoptose foi avaliada por citometria de fluxo. RESULTADOS Os grupos glicose alta e glicose baixa foram submetidos à hipóxia-reoxigenação. O grupo de baixa glicose desenvolveu apenas danos celulares ligeiros, apoptose e uma resposta inflamatória. Em contraste, no grupo de alta glicose, uma lesão equivalente de hipóxia-reoxigenação provocou danos celulares graves, apoptose e uma resposta inflamatória. A expressão de TLR7 e suas proteínas relacionadas foi medida no grupo de alta glicose antes e após a hipóxia-reoxigenação. O grupo de alta glicose exibiu maiores aumentos na expressão de TLR7 após hipóxia-reoxigenação do que o grupo de baixa glicose. Além disso, a expressão de TLR7 e suas proteínas relacionadas após a hipóxia-reoxigenação foi maior no grupo com alto nível de glicose do que no grupo com baixo nível de glicose. A inibição do TLR7 fornece proteção significativa contra a lesão isquêmica no diabetes. CONCLUSÃO Nossos resultados sugerem que o diabetes aumenta a vulnerabilidade à lesão renal induzida por isquemia. Essa vulnerabilidade acrescida tem por origem uma resposta inflamatória aumentada envolvendo a via de transdução de sinal do TLR7.

N-acetyl-l-cysteine exacerbates kidney dysfunction caused by a chronic high-sodium diet in renal ischemia and reperfusion rats.

AIMS: To investigate the effect of long-term N-acetyl-l-cysteine (NAC) treatment in Wistar rats subjected to renal ischemia and reperfusion (IR) and a chronic high­sodium diet (HSD). MAIN METHODS: Adult male Wistar rats received an HSD (8.0% NaCl) or a normal­sodium diet (NSD; 1.3% NaCl) and NAC (600 mg/L) or normal drinking water starting at 8 weeks of age. At 11 weeks of age, the rats from both diet and NAC or water treatment groups underwent renal IR or Sham surgery and were followed for 10 weeks. The study consisted of six animal groups: NSD + Sham + water; NSD + IR + water; NSD + IR + NAC; HSD + Sham + water; HSD + IR + water; and HSD + IR + NAC. KEY FINDINGS: Tail blood pressure (tBP) increased with IR and NAC treatment in the NSD group but not in the HSD group. The serum creatinine level was higher after NAC treatment in both diet groups, and creatinine clearance was decreased in only the HSD + IR + NAC group. Albuminuria increased in the HSD + IR + water group and decreased in the HSD + IR + NAC group. Kidney mass was increased in the HSD + IR group and decreased with NAC treatment. Renal fibrosis was prevented with NAC treatment and cardiac fibrosis was decreased with NAC treatment in the HSD + IR group. SIGNIFICANCE: NAC treatment promoted structural improvements, such as decreased albuminuria and fibrosis, in the kidney and heart. However, NAC could not recover kidney function or blood pressure from the effects of IR associated with an HSD. Therefore, in general, long-term NAC treatment is not effective and is deleterious to recovery of function after kidney injury.

Revisión Bibliográfica: Glicocálix Endotelial como Blanco de Agresión del Fenómeno Isquemia Reperfusión / Bibliographic Review: Endothelial Glycocalyx as Target of Aggression of the Ischemia-Reperfusion Injury

El glicocálix endotelial es una estructura rica en glucosaminoglicanos, proteoglicanos y glucoproteínas que recubre el endotelio vascular; además de ser una estructura de protección, al estar en contacto directo con la sangre se convierte en el blanco de agresión de diversos mecanismos fisiopatológicos. El fenómeno isquemia-reperfusión se presenta comúnmente en varias entidades del paciente crítico, incluyendo: eventos cerebro vasculares isquémicos, síndrome coronario agudo, sepsis y choque en sus distintos tipos, traumatismos mayores, cirugía y trasplante. Las complicaciones derivadas de este fenómeno son múltiples y dependientes del sitio de presentación; el común denominador es la disfunción microvascular que potencialmente podría desencadenar un fallo multisistémico. El objetivo de esta revisión bibliográfica fue realizar una actualización de los conocimientos en relación a la injuria del glicocálix endotelial durante el fenómeno isquemia-reperfusión.(au)

The endothelial glycocalyx is a structure rich in glycosaminoglycans, proteoglycans and glycoproteins that cover vascular endothelium; in addition of being a protective structure, the direct contact with blood turns it the target of aggression of multiple physiopathological mechanisms. The ischemia-reperfusion injury commonly presents in several critical care entities, including: ischemic stroke, acute coronary syndrome, sepsis and shock, major trauma, surgery and transplantation. Complications are multiple and dependent of the site of presentation; the common denominator is microvascular dysfunction that could potentially trigger multiple organ dysfunction syndrome. The aim of this bibliographic review was to update the knowledge regarding endothelial glycocalyx damage and ischemia-reperfusion injury.(au)

Neonatal hypoxia-ischemia caused mild motor dysfunction, recovered by acrobatic training, without affecting morphological structures involved in motor control in rats.

The aim of this study was to evaluated motor function and morphological aspects of the components involved in motor control (sensorimotor cortex, spinal cord, sciatic nerve, neuromuscular junctions and skeletal muscle) in male Wistar rats exposed to a model of neonatal hypoxic-ischemic encephalopathy (HIE) and the possible influence of different physical exercise protocols - treadmill and acrobatic. Male Wistar rats at the 7th post-natal day (PND) were submitted to the HIE model and from the 22nd until 60th PND the exercise protocols (treadmill or acrobatic training) were running. After the training, the animals were evaluated in Open Field, Ladder Rung Walking and Rotarod tasks and after samples of the motor control components were collected. Our results evidenced that the acrobatic training reversed the hyperactivity and anxiety, caused locomotion improvement and decreased brain atrophy in HIE animals. We did not find morphological differences on sensorimotor cortex, spinal cord, sciatic nerve, neuromuscular junctions and skeletal muscle in the animals submitted to HIE model. These intriguing data support the statement of the Rice-Vannucci model does not seem to reproduce, in structures involved in control function, the damage found in humans that suffer HIE. Regarding the protocols of exercise, we proposed that the acrobatic exercise could be a good therapeutic option especially in children affected by neonatal HIE and can be responsible for good results in cognitive and motor aspects.

Use of intravenous alprostadil in patients with severe critical ischemia of the lower limbs.

OBJECTIVES: To determine the indications for the use, potential benefits, and adverse reactions of alprostadil in a group of Colombian patients. METHODS: A retrospective cross-sectional study was conducted in patients diagnosed with critical limb ischemia who received alprostadil in five hospitals in Colombia between September 2011 and July 2017. We reviewed the clinical records of each patient to obtain the sociodemographic and pharmacological variables, clinical stages, complications, comorbidities, reported effectiveness and adverse reactions. RESULTS: Sixty-one patients treated with alprostadil were evaluated; 50.8% of patients were men, and the average age of 72.5 ± 10.7 years. A total of 86.9% of patients were hypertensive, and 65.6% were diabetic. A total of 77.0% presented ulceration, and this condition was considered as a diabetic foot in 57.4% of patients. A total of 81.9% of patients were classified as Fontaine stage 4; 60.7% received therapy as initially indicated, with an average of 19 days of alprostadil use. Regarding the therapy results, 58.0% of the patients with ulcers or trophic lesions showed improvement, 86.2% showed improvement of pain, and the limb was saved in 72.1% of patients. CONCLUSIONS: Critical limb ischemia was presented by patients with advanced age and high cardiovascular risk who were treated during severe and advanced stages where therapeutic options are limited. Treatment with alprostadil achieved satisfactory results with improvement in ulcers, pain, and limb salvage rates in this series of patients.

Ischemic preconditioning delays the time of exhaustion in cycling performance during the early but not in the late phase

Aims: To investigate the early and late ischemic preconditioning (IPC) effect on the trained cyclists' performance during incremental cycling test until exhaustion. Methods: Twenty-one male cyclists allocated to an IPC (2 x 5-min of blood flow occlusion at 50 mm Hg above systolic pressure followed + 5-min of deflation), SHAM (2 x 5-min at 20 mm Hg) or control (CON; no occlusion) interventions, performed three incremental cycling test (ICT) until exhaustion on separate days. The ICT were conducted pre interventions (baseline), 5-min and 24-h after interventions. The heart rate (HR) and power output (PO) were recorded during all ICT. Results: The IPC group increased ICT performance (4.4 ± 4.0 %; effect size (ES) = 0.27) 5-min post intervention, accompanied by HR mean reduction, compared to baseline (p < 0.05). However, there were no changes in SHAM (2.2 ± 4.2%; ES = 0.07) and CON (2.9 ± 5.0%; ES = 0.06) groups. In 24-h post intervention, SHAM (0.2 ± 4.7%; ES = 0.02) and CON (-1.0 ±1.6; ES = 0.03) maintained (p > 0.05) and IPC group decreased the performance (-4.6 ± 3.6 %; ES = 0.16) compared to 5-min post intervention (p < 0.05), but all groups were similar to baseline (p > 0.05). There were no difference (p > 0.05) among groups for PO peak, HR and ICT performance in all moments (baseline, 5-min and 24-h post intervention). Conclusion: The IPC increases early but not late incremental cycling test performance.(AU)

Declines in exercise performance are prevented 24 hours after post-exercise ischemic conditioning in amateur cyclists.

Brief moments of blood flow occlusion followed by reperfusion may promote enhancements in exercise performance. Thus, this study assessed the 24-h effect of post-exercise ischemic conditioning (PEIC) on exercise performance and physiological variables in trained cyclists. In a randomized, single-blind study, 28 trained cyclists (27.1 ± 1.4 years) performed a maximal incremental cycling test (MICT). The outcome measures were creatine kinase (CK), muscle soreness and perceived recovery status, heart rate, perceived exertion and power output. Immediately after the MICT, the cyclists performed 1 of the following 4 interventions: 2 sessions of 5-min occlusion/5-min reperfusion (PEIC or SHAM, 2 x 5) or 5 sessions of 2-min occlusion/2-min reperfusion (PEIC or SHAM, 5 x 2). The PEIC (50 mm Hg above the systolic blood pressure) or SHAM (20 mm Hg) treatment was applied unilaterally on alternating thighs. At 24 h after the interventions, a second MICT was performed. In all the groups, the CK levels were increased compared with the baseline (p < 0.05) after the 24-h MICT. The PEIC groups (2 x 5 and 5 x 2) felt more tired at 24 h post intervention (p < 0.05). However, both PEIC groups maintained their performance (2 x 5: p = 0.819; 5 x 2: p = 0.790), while the SHAM groups exhibited decreased performance at 24 h post intervention compared to baseline (2 x 5: p = 0.015; 5 x 2: p = 0.045). A decrease in the maximal heart rate (HR) was found only in the SHAM 2 x 5 group (p = 0.015). There were no other significant differences in the heart rate, power output or perceived exertion after 24 h compared with the baseline values for any of the interventions (p > 0.05). In conclusion, PEIC led to maintained exercise performance 24 h post intervention in trained cyclists.