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

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

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

Effect of superfine powder and aqueous extract of Polygonati Rhizoma on rats with natural perimenopausal syndrome / 中国中药杂志

This study aims to examine the effect of superfine powder and aqueous extract of Polygonati Rhizomaon on natural perimenopausal syndrome in rats and explore the underlying mechanism. To be specific, a total of 60 female SD rats(14-15 months old) with estrous cycle disorder were screened by the vaginal smear and randomized into model control group, β-estradiol 3-benzoate group(0.1 mg·kg~(-1)), superfine powder of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)) and aqueous extract of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)), and another 10 female SD rats(14-15 months old) were selected as the youth control group. The administration lasted 6 weeks. Then the perimenopausal syndrome-related indexes such as body temperature, microcirculatory blood flow of face and ear, vertigo period, salivary secretion, grip force, and bone strength were determined and open field test was conducted. The immune system-related indexes such as the wet weight and index of thymus and spleen, percentage of T lymphocytes and subgroups in peripheral blood, and hematological indexes were measured. In addition, the ovary-related indexes such as estrous cycle, the wet weight and index of uterus and ovary, ovarian tissue morphology, and cell apoptosis were determined. Moreover, hypothalamus-pituitary-ovary axis(HPO)-related indexes such as serum sex hormone levels, cytochrome P450 family 11 subfamily A member 1(CYP11A1), cytochrome P450 family 19 subfamily A member 1(CYP19A1), and cytochrome P450 family 17 subfamily A member 1(P450 17A1) in ovarian tissue were measured. The results showed that the superfine powder and aqueous extract of Polygonati Rhizoma significantly decreased body temperature(anal, facial and dorsal temperature), microcirculatory blood flow in the ear, and vertigo period, increased salivary secretion, grip force, bone strength, total distance and total speed in the open field test, wet weight and index of thymus and spleen, lymphocyte ratio, CD3~+ level, and CD4~+/CD8~+ ratio, reduced neutrophil number and ratio, estrous cycle disorder ratio, and number of ovarian apoptotic cells, raised wet weight and index of uterus, wet weight of ovary, levels of inhibin B(INHB), estradiol(E_2), anti-müllerian hormone(AMH), and ovarian CYP11A1 and CYP19A1, decreased follicle-stimulating hormone(FSH) and luteinizing hormone(LH) content, and improved ovarian tissue morphology. It is suggested that the superfine powder and aqueous extract of Polygonati Rhizoma can improve the symptoms associated with natural perimenopausal syndrome in rats and enhance ovarian function and immune function. The mechanism is that they regulate HPO axis function by increasing estrogen synthesis.

Correlation between four limbs perfusion index and lactic acid in patients with severe neurological diseases / 中华危重病急救医学

OBJECTIVE@#To observe the correlation between the four limbs perfusion index (PI) and blood lactic acid in patients with neurosis, and evaluate the predictive value of PI on microcirculation perfusion metabolic disorder in patients with neurosis.@*METHODS@#A prospective observational study was conducted. Adult patients admitted to the department of neurological intensive care unit (NICU) of the First Affiliated Hospital of Xinjiang Medical University from July 1 to August 20 in 2020 were enrolled. Under the condition of indoor temperature controlled at 25 centigrade, all patients were placed in the supine position, and the blood pressure, heart rate, PI of both fingers and thumb toes and arterial blood lactic acid were measured within 24 hours and 24-48 hours after NICU. The difference of four limbs PI at different time periods and its correlation with lactic acid were compared. Receiver operator characteristic curve (ROC curve) was used to evaluate the predictive value of four limbs PI on patients with microcirculatory perfusion metabolic disorder.@*RESULTS@#A total of 44 patients with neurosis were enrolled, including 28 males and 16 females; average age (61.2±16.5) years old. There were no significant differences in PI of the left index finger and the right index finger [2.57 (1.44, 4.79) vs. 2.70 (1.25, 5.33)], PI of the left toe and the right toe [2.09 (0.85, 4.76) vs. 1.88 (0.74, 4.32)] within 24 hours after entering the NICU, and the PI of the left index finger and the right index finger [3.17 (1.49, 5.07) vs. 3.14 (1.33, 5.36)], PI of the left toe and the right toe [2.07 (0.75, 5.20) vs. 2.07 (0.68, 4.67)] at 24-48 hours after NICU admission (all P > 0.05). However, compared to the PI of the upper and lower limbs on the same side, except for the 24-48 hours after ICU of the PI difference between the left index finger and the left toe (P > 0.05), the PI of the toe was lower than that of the index finger at the other time periods (all P < 0.05). The correlation analysis showed that the PI value of four limbs of patients in both time periods were significantly negatively correlated with arterial blood lactic acid (the r values of the left index finger, the right index finger, the left toe and the right toe were -0.549, -0.482, -0.392 and -0.343 respectively within 24 hours after entering the NICU; the r values of the left index finger, the right index finger, the left toe and the right toe were -0.331, -0.292, -0.402 and -0.442 respectively after entering the NICU 24-48 hours, all P < 0.05). Taking lactic acid ≥ 2 mmol/L as the diagnostic standard for metabolic disorder of microcirculation perfusion (total 27 times, accounting for 30.7%). The efficacy of four limbs PI in predicting microcirculation perfusion metabolic disorder were compared. ROC curve analysis showed that the area under the curve (AUC) and 95% confidence interval (95%CI) of left index finger, right index finger, left toe and right toe predicting microcirculation perfusion metabolic disorder were 0.729 (0.609-0.850), 0.767 (0.662-0.871), 0.722 (0.609-0.835), 0.718 (0.593-0.842), respectively. There was no significant difference in AUC compare with each other (all P > 0.05). The cut-off value of PI of right index finger for predicting microcirculation perfusion metabolic disorder was 2.46, the sensitivity was 70.4%, the specificity was 75.4%, the positive likelihood ratio was 2.86, and the negative likelihood ratio was 0.30.@*CONCLUSIONS@#There are no significant differences in PI of bilateral index fingers, bilateral toes in patients with neurosis. However, unilateral upper and lower limbs showed lower PI in the toe than in the index finger. There is a significantly negatively correlation between PI and arterial blood lactic acid in all four limbs. PI can predict the metabolic disorder of microcirculation perfusion, and its cut-off value is 2.46.

Design and implementation of a modular pulse wave preprocessing and analysis system based on a new detection algorithm / 生物医学工程学杂志

As one of the standard electrophysiological signals in the human body, the photoplethysmography contains detailed information about the blood microcirculation and has been commonly used in various medical scenarios, where the accurate detection of the pulse waveform and quantification of its morphological characteristics are essential steps. In this paper, a modular pulse wave preprocessing and analysis system is developed based on the principles of design patterns. The system designs each part of the preprocessing and analysis process as independent functional modules to be compatible and reusable. In addition, the detection process of the pulse waveform is improved, and a new waveform detection algorithm composed of screening-checking-deciding is proposed. It is verified that the algorithm has a practical design for each module, high accuracy of waveform recognition and high anti-interference capability. The modular pulse wave preprocessing and analysis software system developed in this paper can meet the individual preprocessing requirements for various pulse wave application studies under different platforms. The proposed novel algorithm with high accuracy also provides a new idea for the pulse wave analysis process.

Mean platelet volume and neutrophil to lymphocyte ratio in patients with tinnitus: a case-control study / Volume plaquetário médio e relação neutrófilos/linfócitos em pacientes com zumbido: estudo de caso-controle

Abstract Introduction: Different theories have been proposed on the etiology of tinnitus, including metabolic and audiologic causes. We suggest that mean platelet volume and neutrophil to lymphocyte ratio levels change in tinnitus, indicating microcirculatory disturbance and inflammatory process in the etiopathogenesis of tinnitus. Objectives: We aimed to evaluate the mean platelet volume and neutrophil to lymphocyte ratio in patients with tinnitus in comparison to healthy controls. Methods: Retrospective case-control study. Two-hundred and eighty-seven patients aged 18-59 years and diagnosed with tinnitus in the Ear, Nose, and Throat Clinic between December 2014 and May 2017 (patient group) and 275 healthy individuals who applied for a hearing screening within the same time period (control group). Demographics, concomitant diseases, laboratory results, and audiometric data were recorded. Mean platelet volume and neutrophil to lymphocyte ratio were the outcome measures. Patients with hearing loss due to presbycusis or another reasons, and patients with anatomical disorders in the external and middle ear were excluded from the study by using physical examinations, pure audio audiometry results and radiological imaging. The upper age limit was set at 59 to exclude presbycusis patients. Results: The ratio of female patients was higher in patient group than control group (58.5%, n = 168 vs. 49.4%, n= 127; respectively; p = 0.033). The mean age of patient group was significantly higher than those of control group (44.89 ± 10.96 years and 38.37 ± 10.65 years, respectively; p = 0.001). The percentage of subjects with high mean platelet volume level was significantly higher in patient group than control group (9.4%, n = 27, and 3.1%, n = 8 respectively; p = 0.008). The mean neutrophil to lymphocyte ratio was higher in patients with tinnitus than control group (1.95 ± 1.02 and 1.67 ±0.57, p = 0.012). A neutrophil to lymphocyte ratio level of 2.17 and above is associated with 1.991 times higher risk of tinnitus (odds ratio = 1.99, 95% confidence interval 1.31-3.02). Conclusion: High mean platelet volume and neutrophil to lymphocyte ratio values are associated with idiopathic tinnitus, suggesting the role of vascular pathologies in etiology of tinnitus. Tinnitus may be a sign of underlying systemic or local disorders. Therefore, patients with tinnitus should undergo detailed evaluation including hematological indices.

Resumo Introdução: Diferentes teorias já foram propostas sobre a etiologia do zumbido, inclusive causas metabólicas e audiológicas. Acreditamos que os níveis do volume plaquetário médio e da relação neutrófilos/linfócitos se alteram no zumbido, sugerem distúrbio microcirculatório e processo inflamatório na etiopatogenia do zumbido. Objetivo: Avaliar o volume plaquetário médio e a relação neutrófilos/linfócitos em pacientes com zumbido em comparação com controles saudáveis. Método: Estudo de caso-controle retrospectivo, com 287 pacientes entre 18 e 59 anos e diagnosticados com zumbido na Clínica de Otorrinolaringologia entre dezembro de 2014 e maio de 2017 (grupo pacientes) e 275 indivíduos saudáveis que solicitaram uma triagem auditiva no mesmo período (grupo controle). Foram registrados dados demográficos, doenças concomitantes, resultados laboratoriais e dados audiométricos. O volume plaquetário médio e a relação neutrófilos/linfócitos foram as medidas de desfecho. Pacientes com perda auditiva por presbiacusia ou por outros motivos e pacientes com distúrbios anatômicos na orelha externa e média foram excluídos do estudo por meio de exame físico, resultados de audiometria tonal pura e imagens radiológicas. O limite de idade superior foi fixado em 59 anos para excluir pacientes com presbiacusia. Resultados: A proporção de pacientes do sexo feminino foi maior no grupo de pacientes do que no grupo controle (58,5%, n = 168 vs. 49,4%, n = 127; respectivamente; p = 0,033). A média de idade do grupo de pacientes era significantemente maior do que a do grupo controle (44,89 ± 10,96 anos e 38,37 ± 10,65 anos, respectivamente; p = 0,001). A porcentagem de indivíduos com nível alto de volume plaquetário médio foi significantemente maior no grupo de pacientes do que no grupo controle (9,4%, n = 27 e 3,1%, n = 8, respectivamente; p = 0,008). A relação neutrófilos/linfócitos média foi maior nos pacientes com zumbido do que no grupo controle (1,95 ± 1,02 e 1,67 ±0,57, p = 0,012). Um nível de relação neutrófilos/linfócitos de 2,17 e acima está associado a um risco 1,991 vez maior de zumbido (odds ratio = 1,99, Intervalo de Confiança de 95% 1,31 a 3,02). Conclusão: Altos valores de volume plaquetário médio e relação neutrófilos/linfócitos estão associados ao zumbido idiopático, sugerem o papel de doenças vasculares na etiologia do zumbido. O zumbido pode ser um sinal de distúrbios sistêmicos ou locais subjacentes. Portanto, pacientes com zumbido devem ser submetidos a uma avaliação detalhada, inclusive índices hematológicos.

Index of microcirculatory resistance: state-of-the-art and potential applications in computational simulation of coronary artery disease / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The dysfunction of coronary microcirculation is an important cause of coronary artery disease (CAD). The index of microcirculatory resistance (IMR) is a quantitative evaluation of coronary microcirculatory function, which provides a significant reference for the prediction, diagnosis, treatment, and prognosis of CAD. IMR also plays a key role in investigating the interaction between epicardial and microcirculatory dysfunctions, and is closely associated with coronary hemodynamic parameters such as flow rate, distal coronary pressure, and aortic pressure, which have been widely applied in computational studies of CAD. However, there is currently a lack of consensus across studies on the normal and pathological ranges of IMR. The relationships between IMR and coronary hemodynamic parameters have not been accurately quantified, which limits the application of IMR in computational CAD studies. In this paper, we discuss the research gaps between IMR and its potential applications in the computational simulation of CAD. Computational simulation based on the combination of IMR and other hemodynamic parameters is a promising technology to improve the diagnosis and guide clinical trials of CAD.

Inspiration from the research advances in microcirculatory dysfunction to the treatment of burn shock and burn septic shock / 中华烧伤杂志

Microcirculatory dysfunction is an important pathophysiological change of shock. In the last decade, many researches on the mechanism of microcirculatory dysfunction have been involved in areas such as the glycocalyx damage of vascular endothelial cells, macrocirculation- microcirculation discoupling, vascular hyporeactivity, and microcirculation monitoring. Accordingly, this paper discussed how these research findings can be applied to burn patients, with the aim of alerting the clinicians to improving microcirculation, and maintaining hemodynamic coordination during the treatment of burn shock and burn septic shock. In addition, with the development of accurate and reliable microcirculation monitoring techniques, it is necessary to carry out multi-center clinical trials to reveal the clinical significance of target-oriented shock resuscitation protocol combining macrocirculatory and microcirculatory parameters.

Effects of dexmedetomidine on hemodynamic, oxygenation, microcirculation, and inflammatory markers in a porcine model of sepsis

Purpose: To determine whether dexmedetomidine aggravates hemodynamic, metabolic variables, inflammatory markers, and microcirculation in experimental septic shock. Methods: Twenty-four pigs randomized into: Sham group (n = 8), received saline; Shock group (n = 8), received an intravenous infusion of Escherichia coli O55 (3 × 109 cells/mL, 0.75 mL/kg, 1 hour); Dex-Shock group (n = 8), received bacteria and intravenous dexmedetomidine (bolus 0.5 mcg/kg followed by 0.7 mcg/kg/h). Fluid therapy and/ornorepinephrine were administered to maintain a mean arterial pressure > 65 mmHg. Hemodynamic, metabolic, oxygenation, inflammatory markers, and microcirculation were assessed at baseline, at the end of bacterial infusion, and after 60, 120, 180, and 240 minutes. Results: Compared to Shock group, Dex-Shock group presented a significantly increased oxygen extraction ratio at T180 (23.1 ± 9.7 vs. 32.5 ± 9.2%, P = 0.0220), decreased central venous pressure at T120 (11.6 ± 1 vs. 9.61 ± 1.2 mmHg, P = 0.0214), mixed-venous oxygen saturation at T180 (72.9 ± 9.6 vs. 63.5 ± 9.2%, P = 0.026), and increased plasma lactate (3.7 ± 0.5 vs. 5.5 ± 1 mmol/L, P = 0.003). Despite the Dex-Shock group having a better sublingual vessel density at T240 (12.5 ± 0.4 vs. 14.4 ± 0.3 mL/m2; P = 0.0003), sublingual blood flow was not different from that in the Shock group (2.4 ± 0.2 vs. 2.4 ± 0.1 mL/kg, P = 0.4418). Conclusions: Dexmedetomidine did not worsen the hemodynamic, metabolic, inflammatory, or sublingual blood flow disorders resulting from septic shock. Despite inducing a better sublingual vessel density, dexmedetomidine initially and transitorily increased the mismatch between oxygen supply and demand.

Influence of Acupuncture on Microcirculation Perfusion of Pericardium Meridian and Heart in Acute Myocardial Ischemia Model Rats / 中国结合医学杂志

OBJECTIVE@#To observe the influence of acupuncture on microcirculation perfusion of the pericardium meridian and heart in acute myocardial ischemia (AMI) rats and evaluate whether acupuncture can simultaneously affect the meridians and corresponding viscera. Additionally, acupoints at different meridians were compared and whether they exert the same effects was discussed.@*METHODS@#Totally 32 Sprague-Dawley rats were subjected to left anterior descending (LAD) ligation to develop an AMI model. Rats were divided into 4 groups, including AMI, acupuncture Neiguan (PC 6), Lieque (LU 7) and Qiansanli (LI 10) groups (n=8). Eight rats received only thoracotomy (sham-operated group). The rats in the acupuncture groups received manual acupuncture at PC 6, LU 7 and LI 10 acupoints for 15 min, respectively. The microcirculation perfusion of pericardium meridian and heart was monitored by laser speckle perfusion imager (LSPI) before, during and after acupuncture manipulation for 15 min. Subsequently, the perfusion unit (PU) was calculated and analyzed by PSI System.@*RESULTS@#After LAD, compared to pre-acupuncture stage, the heart microcirculation perfusion (HMP) in the AMI group decreased continuously at during-acupuncture (P>0.05) and post-acupuncture stages (P0.05). Compared to pre-acupuncture stage, the PMP and HMP in PC 6 group significantly increased during acupuncture manipulation (both P0.05); however, they were significantly reduced after acupuncture manipulation (both P<0.05). Additionally, HMP of LI 10 group was decreased significantly during acupuncture, especially compared to pre-acupuncture stage (P<0.05).@*CONCLUSIONS@#Acupuncture at PC 6 obviously increased the PMP and HMP in AMI rats, and the effects were superior to at LU 7 and LI 10 acupoints. It was further confirmed that acupuncture promoted qi and blood circulation, indicating that acupoint specificity exists and features a meridian-propagated effect.

Influence of Microcirculatory Dysfunction on Myocardial Injury after Cardiopulmonary Resuscitation / 生物医学与环境科学（英文）

Objective@#This study aimed to examine the effects of microcirculatory dysfunction and 654-1 intervention after cardiopulmonary resuscitation on myocardial injury.@*Methods@#Landrace pigs were divided into a sham operation group (S group, n= 6), ventricular fibrillation control group (VF-C group, n= 8) and 654-1 intervention group (VF-I group, n= 8). Hemodynamics was recorded at baseline, at recovery of spontaneous circulation (ROSC), and 1 h, 2 h, 4 h and 6 h thereafter. Sidestream dark field (SDF) technology was used to evaluate and monitor the microcirculation flow index, total vessel density, perfusion vessel ratio, De-Backer score, and perfusion vessel density in animal viscera at various time points.@*Results@#After administration of 654-1 at 1.5 h post-ROSC, the hemodynamics in the VF-I group, as compared with the VF-C group, was significantly improved. The visceral microcirculation detected by SDF was also significantly improved in the VF-I group. As observed through electron microscopy, significantly less myocardial tissue injury was present in the VF-I group than the VF-C group.@*Conclusion@#Administration of 654-1 inhibited excessive inflammatory by improving the state of visceral microcirculation.

Resuscitation fluids as drugs: targeting the endothelial glycocalyx / 中华医学杂志(英文版)

Fluid resuscitation is an essential intervention in critically ill patients, and its ultimate goal is to restore tissue perfusion. Critical illnesses are often accompanied by glycocalyx degradation caused by inflammatory reactions, hypoperfusion, shock, and so forth, leading to disturbed microcirculatory perfusion and organ dysfunction. Therefore, maintaining or even restoring the glycocalyx integrity may be of high priority in the therapeutic strategy. Like drugs, however, different resuscitation fluids may have beneficial or harmful effects on the integrity of the glycocalyx. The purpose of this article is to review the effects of different resuscitation fluids on the glycocalyx. Many animal studies have shown that normal saline might be associated with glycocalyx degradation, but clinical studies have not confirmed this finding. Hydroxyethyl starch (HES), rather than other synthetic colloids, may restore the glycocalyx. However, the use of HES also leads to serious adverse events such as acute kidney injury and bleeding tendencies. Some studies have suggested that albumin may restore the glycocalyx, whereas others have suggested that balanced crystalloids might aggravate glycocalyx degradation. Notably, most studies did not correct the effects of the infusion rate or fluid volume; therefore, the results of using balanced crystalloids remain unclear. Moreover, mainly animal studies have suggested that plasma may protect and restore glycocalyx integrity, and this still requires confirmation by high-quality clinical studies.

Peripapillary microvascular parameters in unilateral open-angle glaucoma using the optical coherence tomography-angiography

Objective@#This study compared the peripapillary retinal nerve fiber layer (pRNFL) microangiographic properties [vessel area density (VAD) and blood flux index (BFI)] of unilateral open-angle glaucomatous eyes to contralateral eyes-at-risk, and to eyes of healthy age- and sex-matched subjects.@*Methods@#This was a single-center, case-control study of Filipinos diagnosed with unilateral primary openangle glaucoma (POAG) or normal-tension glaucoma (NTG). Mean overall and quadrantal VAD and BFI of the three groups were measured with optical coherence tomography- angiography (OCT-A). Area under the receiver operating characteristic (AROC) was used to measure diagnostic ability.@*Results@#Twenty-two (22) glaucomatous subjects (15 POAG and 7 NTG eyes), 22 contralateral eyes-at-risk, and 22 normal eyes from age- and sex-matched control subjects completed the study. Eyes with glaucoma showed lower mean overall VAD (40%) and BFI (0.37) compared to eyes-at-risk (44.4% and 0.42, respectively; p <0.001) and control eyes (45.6% and 0.44, respectively; p <0.001). Mean VAD and BFI values of eyes-at-risk and control groups did not significantly differ from each other. Overall pRNFL thickness showed highest diagnostic accuracy for glaucoma (AROC = 0.97), followed by VAD (0.94), and BFI (0.88) (p=0.46).@*Conclusion@#VAD and BFI were significantly diminished in unilateral open-angle glaucoma, suggesting that the utility of OCT-A in the detection of glaucoma is comparable to pRNFL thickness.

Protective Mechanism of Electroacupuncture on Peripheral Neurotoxicity Induced by Oxaliplatin in Rats / 中国结合医学杂志

OBJECTIVE@#To study the effect of electroacupuncture (EA) on oxaliplatin-induced peripheral neuropathy (OIPN) in rats.@*METHODS@#Male Sprague-Dawley rats were equally divided into 3 groups using a random number table: the control group, the OIPN group, and the EA (OIPN + EA) group, with 10 rats in each. The time courses of mechanical, cold sensitivity, and microcirculation blood flow intensity were determined. The morphology of the dorsal root ganglion (DRG) was observed by electron microscopic examination. The protein levels of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the transient receptor potential (TRP) protein family in DRGs were assayed by Western blot.@*RESULTS@#EA treatment significantly reduced mechanical allodynia and cold allodynia in OIPN rats (P<0.01). Notably, oxaliplatin treatment resulted in impaired microcirculatory blood flow and pathomorphological defects in DRGs (P<0.01). EA treatment increased the microcirculation blood flow and attenuated the pathological changes induced by oxaliplatin (P<0.01). In addition, the expression levels of Nrf2 and HO-1 were down-regulated, and the TRP protein family was over-expressed in the DRGs of OIPN rats (P<0.01). EA increased the expression levels of Nrf2 and HO-1 and decreased the level of TRP protein family in DRG (P<0.05 or P<0.01).@*CONCLUSION@#EA may be a potential alternative therapy for OIPN, and its mechanism may be mainly mediated by restoring the Nrf2/HO-1 signaling pathway.

Comparação entre Dois Escores de Risco quanto à Predição de Obstrução Microvascular Coronariana durante a Intervenção Percutânea Primária / The Comparison between Two Risk Scores as for the Prediction of Coronary Microvascular Obstruction during Primary Percutaneous Intervention

Resumo Fundamento: Para pacientes com infarto do miocárdio com elevação do segmento ST (IAMCST) que sofrem de obstrução coronariana microvascular funcional e estrutural (OCM) subsequente, nenhuma abordagem terapêutica específica e definitiva de atenuação foi comprovada como válida em testes de larga escala atuais, o que destaca a necessidade de abordar seu reconhecimento precoce. Objetivos: Este estudo teve como objetivo comparar o desempenho de dois escores de risco clínico com uma medida objetiva de OCM durante intervenção coronária percutânea (ICP) em casos de IAMCST Métodos: A medição do índice de resistência microcirculatória (IRM) foi realizada e os parâmetros clínicos e angiográficos basais também foram registrados. Os pacientes foram divididos em entre os grupos OM (obstrução microvascular) e NOM (não-obstrução microvascular), de acordo com o valor de IRM pós-procedimento. O risco de OCM foi avaliado para todos os participantes pelos escores preditivos SAK e ATI, respectivamente. Cada sistema foi calculado somando-se as pontuações de todas as variáveis. As curvas de características do operador receptor (ROC) e a área sob a curva (AUC) de dois modelos de risco foram utilizadas para avaliar o desempenho discriminatório. Um ecocardiograma foi realizado sete dias após o procedimento para avaliar a fração de ejeção do ventrículo esquerdo (FEVE). Um valor P bicaudal de <0,05 foi considerado estatisticamente significativo. Resultados: Entre os 65 pacientes elegíveis com IAMCST, 48 foram alocados no grupo NOM e 17 no grupo OM, com uma incidência de OCM de 26,15%. Não houve diferença significativa na AUC entre os dois escores. A FEVE avaliada para o grupo NOM foi maior do que para o grupo OM. Conclusão: Os escores SAK e ATI tiveram bom desempenho para estimar o risco de OCM após ICP primário para pacientes com IAMCST.

Abstract Background: For patients with ST-segment elevation myocardial infarction (STEMI) that are suffering from subsequent coronary microvascular functional and structural obstruction (CMVO), no specific and definitive therapeutic approaches of attenuation have been proven valid in up-to-date large-scale tests, which highlights the urge to address its early recognition. Objectives: This study aimed to compare the performance of two clinical risk scores with an objective measurement of CMVO during percutaneous coronary intervention (PCI) with STEMI. Methods: The Index of Microcirculatory Resistance (IMR) measurement was conducted and the baseline clinical and angiographic parameters were also recorded. The patients were divided into MO (Microvascular obstruction) or NMO (Non-microvascular obstruction) groups according to the post-procedure IMR value. The CMVO risk was evaluated for all participants by SAK and ATI predictive scores, respectively. Each system was calculated by summing the scores of all variables. The receiver operator characteristic (ROC) curves and the area under the curve (AUC) of two risk models were used to evaluate the discriminatory performance. An echocardiography was performed seven days after the procedure to evaluate left ventricular ejection fraction (LVEF). A two-sided P-value of <0.05 was considered statistically significant. Results: Among the 65 eligible STEMI patients, 48 patients were allocated in the NMO group and 17 in the MO group, with a CMVO incidence of 26.15%. There was no significant difference in the AUC between both scores. The LVEF evaluated for the NMO group was higher than that of MO group. Conclusion: Both SAK and ATI scores performed well in estimating CMVO risk after primary PCI for STEMI patients.

Hemodynamic monitoring with two blood gases: "a tool that does not go out of style" / Monitoreo hemodinámico con dos gasometrías: "Una herramienta que no pasa de moda"

Abstract Hemodynamic monitoring of a critically ill patient is an indispensable tool both inside and outside intensive care; we currently have invasive, minimally invasive and non-invasive devices; however, no device has been shown to have a positive impact on the patient's evolution; arterial and venous blood gases provide information on the patient's actual microcirculatory and metabolic status and may be a hemodynamic monitoring tool. We aimed to carry out a non-systematic review of the literature of hemodynamic monitoring carried out through the variables obtained in arterial and venous blood gases. A non-systematic review of the literature was performed in the PubMed, OvidSP and ScienceDirect databases with selection of articles from 2000 to 2019. It was found that there are variables obtained in arterial and venous blood gases such as central venous oxygen saturation (SvcO2), venous-to-arterial carbon dioxide pressure (Δpv-aCO2), venous-to-arterial carbon dioxide pressure/arteriovenous oxygen content difference (Δpv-aCO2/ΔCavO2) that are related to cellular oxygenation, cardiac output (CO), microcirculatory veno-arterial flow and anaerobic metabolism and allow to assess tissue perfusion status. In conclusion, the variables obtained by arterial and venous blood gases allow for non-invasive, accessible and affordable hemodynamic monitoring that can guide medical decision-making in critically ill patients.

Resumen El monitoreo hemodinámico de un paciente en estado crítico es una herramienta indispensable tanto dentro como fuera de la terapia intensiva; actualmente se cuenta con dispositivos invasivos, mínimamente invasivos y no invasivos; sin embargo, ningún dispositivo ha demostrado tener impacto positivo en la evolución del paciente; la gasometría arterial y venosa proporcionan información del estado microcirculatorio y metabólico real del paciente pudiendo ser una herramienta de monitoreo hemodinámico. El objetivo de esta revisión fue realizar una revisión no sistemática de la literatura del monitoreo hemodinámico realizado mediante las variables obtenidas en la gasometría arterial y venosa. Se estudiaron las bases de datos de PubMed, OvidSP y ScienceDirect con selección de artículos del 2000 al 2019. Se encontró que hay variables obtenidas en la gasometría arterial y venosa como la saturación venosa central de oxígeno (SvcO2), la diferencia de presión venoarterial de dióxido de carbono (Δpv-aCO2), la diferencia de presión venoarterial de dióxido de carbono/diferencia del contenido arteriovenoso de oxígeno (Δpv-aCO2/ΔCa-vO2) que están relacionadas con la oxigenación celular, con el gasto cardiaco (GC), con el flujo venoarterial microcirculatorio y con el metabolismo anaerobio que permiten realizar una valoración del estado de perfusión tisular. En conclusión, las variables obtenidas por gasometría arterial y venosa permiten realizar un monitoreo hemodinámico no invasivo, accesible y asequible que pueden guiar la toma de decisiones médicas en el paciente en estado crítico.

Impacto da transfusão de eritrócitos no transporte e no metabolismo de oxigênio em pacientes com sepse e choque séptico: uma revisão sistemática e metanálise / Impact of red blood cell transfusion on oxygen transport and metabolism in patients with sepsis and septic shock: a systematic review and meta-analysis

RESUMO Considera-se que a transfusão de eritrócitos melhora a respiração celular durante o choque séptico. Contudo, seu impacto agudo no transporte e no metabolismo de oxigênio nessa condição ainda é amplamente debatido. O objetivo deste estudo foi avaliar o impacto da transfusão de eritrócitos na microcirculação e no metabolismo do oxigênio em pacientes com sepse e choque séptico. Conduzimos um levantamento nas bases de dados MEDLINE®, Elsevier e Scopus. Incluímos estudos realizados com seres humanos adultos com sepse e choque séptico. Realizamos uma revisão sistemática e metanálise com utilização do modelo de efeitos aleatórios de DerSimonian e Laird. Consideramos significante valor de p < 0,05. Incluíram-se na análise 19 manuscritos, correspondentes a 428 pacientes. As transfusões de eritrócitos se associaram com aumento de 3,7% na média combinada de saturação venosa mista de oxigênio (p < 0,001), diminuição de razão de extração de oxigênio de -6,98 (p < 0,001) e nenhum efeito significante no índice cardíaco (0,02 L/minuto; p = 0,96). Obtiveram-se resultados similares em estudos que incluíram mensurações simultâneas de saturação venosa mista de oxigênio, razão de extração de oxigênio e índice cardíaco. As transfusões de eritrócitos levaram a aumento significante na proporção de pequenos vasos perfundidos (2,85%; p = 0,553), enquanto os parâmetros de oxigenação tissular revelaram aumento significante no índice de hemoglobina tissular (1,66; p = 0,018). Estudos individuais relataram melhoras significantes na oxigenação tissular e nos parâmetros microcirculatórios sublinguais em pacientes com microcirculação alterada na avaliação inicial. A transfusão de eritrócitos pareceu melhorar o metabolismo sistêmico de oxigênio com aparente independência de variações no débito cardíaco. Observaram-se alguns efeitos benéficos para a oxigenação tissular e parâmetros microcirculatórios, em particular em pacientes com alterações iniciais mais graves. São necessários mais estudos para avaliar seu impacto clínico e individualizar as decisões relativas à transfusão.

ABSTRACT Red blood cell transfusion is thought to improve cell respiration during septic shock. Nevertheless, its acute impact on oxygen transport and metabolism in this condition remains highly debatable. The objective of this study was to evaluate the impact of red blood cell transfusion on microcirculation and oxygen metabolism in patients with sepsis and septic shock. We conducted a search in the MEDLINE®, Elsevier and Scopus databases. We included studies conducted in adult humans with sepsis and septic shock. A systematic review and meta-analysis were performed using the DerSimonian and Laird random-effects model. A p value < 0.05 was considered significant. Nineteen manuscripts with 428 patients were included in the analysis. Red blood cell transfusions were associated with an increase in the pooled mean venous oxygen saturation of 3.7% (p < 0.001), a decrease in oxygen extraction ratio of -6.98 (p < 0.001) and had no significant effect on the cardiac index (0.02L/minute; p = 0,96). Similar results were obtained in studies including simultaneous measurements of venous oxygen saturation, oxygen extraction ratio, and cardiac index. Red blood cell transfusions led to a significant increase in the proportion of perfused small vessels (2.85%; p = 0.553), while tissue oxygenation parameters revealed a significant increase in the tissue hemoglobin index (1.66; p = 0.018). Individual studies reported significant improvements in tissue oxygenation and sublingual microcirculatory parameters in patients with deranged microcirculation at baseline. Red blood cell transfusions seemed to improve systemic oxygen metabolism with apparent independence from cardiac index variations. Some beneficial effects have been observed for tissue oxygenation and microcirculation parameters, particularly in patients with more severe alterations at baseline. More studies are necessary to evaluate their clinical impact and to individualize transfusion decisions.

COVID-19: a closer look at the pathology in two autopsied cases. Is the pericyte at the center of the pathological process in COVID-19?

We performed autopsies on two cases of COVID-19. The microcirculations of all organs were the site of the pathological findings. Thrombotic microangiopathy was found in the brain and also the kidneys. Vasculitis was also a feature of the autopsy findings, together with portal triaditis of the liver. The major pathological findings in both cases were fibrin deposits. Within the lung, the fibrin deposits were observed in the alveolar microcirculation in sub-endothelial locations of capillaries, arterioles, post capillary venules, and the adventitia of larger vessels. These fibrin deposits in the lungs occurred at the sites where pericytes are located in these vessels. The pericyte with its high concentration of ACE-2 receptors and its procoagulant state may represent one of the primary sites of action of SARS-CoV-2. A review of pericytes in health and disease is undertaken. COVID-19 is a disease of the microcirculation.

Suitability of the muscle O2 resaturation parameters most used for assessing reactive hyperemia: a near-infrared spectroscopy study / Adequação de parâmetros de ressaturação muscular de O2 mais utilizados na avaliação da hiperemia reativa: um estudo por espectroscopia no infravermelho próximo

Abstract Background There is a spectrum of possibilities for analyzing muscle O2 resaturation parameters for measurement of reactive hyperemia in microvasculature. However, there is no consensus with respect to the responsiveness of these O2 resaturation parameters for assessing reactive hyperemia. Objectives This study investigates the responsiveness of the most utilized muscle O2 resaturation parameters to assess reactive hyperemia in the microvasculature of a clinical group known to exhibit impairments of tissue O2 saturation (StO2). Methods Twenty-three healthy young adults, twenty-nine healthy older adults, and thirty-five older adults at risk of cardiovascular disease (CVD) were recruited. Near-infrared spectroscopy (NIRS) was used to assess StO2 after a 5-min arterial occlusion challenge and the following parameters were analyzed: StO2slope_10s, StO2slope_30s, and StO2slope_until_baseline (upslope of StO2 over 10s and 30s and until StO2 reaches the baseline value); time to StO2baseline and time to StO2max (time taken for StO2 to reach baseline and peak values, respectively); ∆StO2reperfusion (the difference between minimum and maximum StO2 values); total area under the curve (StO2AUCt); and AUC above the baseline value (StO2AUC_above_base). Results Only StO2slope_10s was significantly slower in older adults at risk for CVD compared to healthy young individuals (p < 0.001) and to healthy older adults (p < 0.001). Conversely, time to StO2max was significantly longer in healthy young individuals than in older adult at CVD risk. Conclusions Our findings suggest that StO2slope_10s may be a measure of reactive hyperemia, which provides clinical insight into microvascular function assessment.

Resumo Contexto Existe um espectro de possibilidades na análise dos parâmetros de ressaturação de O2 muscular como uma medida de hiperemia reativa na microvasculatura. No entanto, não há consenso com relação à responsividade desses parâmetros de ressaturação de O2 para avaliação de hiperemia reativa. Objetivos Este estudo investigou a capacidade de resposta dos parâmetros de ressaturação muscular de O2 mais utilizados para avaliar a hiperemia reativa na microvasculatura de um grupo clínico conhecido por apresentar comprometimento da saturação de O2 (StO2). Métodos Foram recrutados 23 jovens saudáveis, 29 idosos saudáveis e 35 idosos com risco para doença cardiovascular. A espectroscopia no infravermelho próximo foi usada para avaliar a StO2 após um teste de oclusão arterial de 5 minutos, no qual os seguintes parâmetros foram analisados: StO2slope_10s, StO2slope_30s e StO2slope_until_baseline (inclinação da StO2 em 10 s, 30 s e até StO2 atingir valores basais); tempo para StO2baseline e tempo para StO2máx (o tempo necessário para StO2 atingir os valores da linha de base e o máximo, respectivamente); ∆StO2reperfusão (a diferença entre o valor de StO2mínimo e StO2máximo); área total sob a curva (StO2AUCt); e área sob a curva acima do valor da linha de base (StO2AUC_above_base). Resultados Apenas StO2slope_10s foi significativamente mais lento em idosos em risco de doença cardiovascular comparados com indivíduos jovens saudáveis (p < 0,001) e idosos saudáveis (p < 0,001). Por outro lado, o tempo para StO2max foi significativamente maior em indivíduos jovens saudáveis do que em idosos em risco de doença cardiovascular. Conclusões Nossos achados sugerem que StO2slope_10s pode ser uma medida de hiperemia reativa, que fornece informações clínicas sobre a avaliação da função microvascular.

Dietary supplementation with whey protein improves systemic microvascular function in heart failure patients: a pilot study

Endothelial dysfunction is a well-known component of the pathophysiology of heart failure (HF), with proven prognostic value. Dietary supplementation with whey protein (WP) has been widely used to increase skeletal muscle mass, but it also has vascular effects, which are less understood. This study aimed to evaluate the effects of WP supplementation on the systemic microvascular function of HF patients. This was a blinded, randomized, placebo-controlled clinical trial that evaluated the effects of 12-week WP dietary supplementation on systemic microvascular function, in patients with HF New York Heart Association (NYHA) classes I/II. Cutaneous microvascular flow and reactivity were assessed using laser speckle contrast imaging, coupled with pharmacological local vasodilator stimuli. Fifteen patients (aged 64.5±6.2 years, 11 males) received WP supplementation and ten patients (aged 68.2±8.8 years, 8 males) received placebo (maltodextrin). The increase in endothelial-dependent microvascular vasodilation, induced by skin iontophoresis of acetylcholine, was improved after WP (P=0.03) but not placebo (P=0.37) supplementation. Moreover, endothelial-independent microvascular vasodilation induced by skin iontophoresis of sodium nitroprusside, was also enhanced after WP (P=0.04) but not placebo (P=0.42) supplementation. The results suggested that dietary supplementation with WP improved systemic microvascular function in patients with HF.

Nailfold capillaroscopy and microvascular involvement in Diabetes Mellitus / Capilaroscopia de leito ungueal e envolvimento microvascular em Diabetes Mellitus

Objective: to study the relationship between microvascular lesions of Diabetes Mellitus and alterations in the nailfold capillaroscopy. Subjects and Methods: cross-sectional study including 140 individuals (70 with Diabetes Mellitus and 70 controls). Epidemiological and clinical variables were collected from patient's charts. Fundus ophthalmoscopy, nailfold capillaroscopy, analysis of microalbuminuria and renal clearance as well as fasting glycaemia and HbA1c values were studied simultaneously. Results: capillary density was reduced, and vascular dilatation was increased in Diabetes Mellitus patients when compared to controls (both with p<0.0001). In diabetic individuals the number of dermal papillary capillaries/mm3 correlated negatively with microalbuminuria (p=0.02), patient's age (p=0.03), values of HbA1c (p=0.03). Patients with diabetic retinopathy and using antiplatelet agents had lower capillary density (p<0.0001 and 0.04 respectively). Capillary dilatation was associated with disease duration (p=0.04). Conclusion: microvascular disease in Diabetes Mellitus is reflected in nailfold capillaroscopy. Decreased capillary density, increased number of ectasias and increased presence of avascular areas were observed in patients with diabetes when compared to controls. In the present study, capillary density correlated/associate with age, retinopathy, use of antiplatelet medication, HbA1c, microalbuminuria and diabetes duration. Ectasias or dilatations were related to retinopathy, glomerular filtration rate and longer disease duration.

Objetivo: estudar a relação entre lesões microvasculares do Diabetes Mellitus e alterações na capilaroscopia ungueal. Sujeitos e Métodos: estudo transversal incluindo 140 indivíduos (70 com Diabetes Mellitus e 70 controles). Variáveis epidemiológicas e clínicas foram coletadas dos prontuários dos pacientes. A oftalmoscopia de fundo, capilaroscopia ungueal, análise de microalbuminúria e depuração renal, bem como glicemia de jejum e valores de HbA1c foram estudados simultaneamente. Resultados: a densidade capilar foi reduzida e a dilatação vascular aumentada em pacientes com Diabetes Mellitus quando comparados aos controles (ambos com p <0,0001). Em indivíduos diabéticos, o número de capilares papilares dérmicos/ mm3 correlacionou-se negativamente com microalbuminúria (p = 0,02), idade do paciente (p = 0,03), valores de HbA1c (p = 0,03). Pacientes com retinopatia diabética e em uso de antiagregante plaquetário apresentaram menor densidade capilar (p <0,0001 e 0,04 respectivamente). A dilatação capilar foi associada ao tempo de doença (p = 0,04). Conclusão: a doença microvascular no Diabetes Mellitus reflete-se na capilaroscopia ungueal. Diminuição da densidade capilar, aumento do número de ectasias e aumento da presença de áreas avasculares foram observados em pacientes com diabetes quando comparados aos controles. No presente estudo, a densidade capilar se correlacionou/ se associou com idade, retinopatia, uso de antiagregante plaquetário, HbA1c, microalbuminúria e tempo de diabetes. Ectasias ou dilatações foram relacionadas à retinopatia, à taxa de filtração glomerular e a maior duração da doença.