Angiotensin-converting enzyme 2 activation attenuates inflammation and oxidative stress in brain death donor followed by rat lung transplantation.

Brain death (BD) provides most of the donor organs destined for lung transplantation (LTx). However, the organs may be affected by inflammatory and oxidative processes. Based on this, we hypothesize that the angiotensin-converting enzyme 2 (ACE2) activation can reduce the lung injury associated with LTx. 3 h after BD induction, rats were injected with saline (BD group) or an ACE2 activator (ACE2a group; 15 mg/kg-1) and kept on mechanical ventilation for additional 3 h. A third group included a control ventilation (Control group) prior to transplant. After BD protocol, left LTx were performed, followed by 2 h-reperfusion. ACE2 activation was associated with better oxygenation after BD management (p = 0.01), attenuating edema (p = 0.05) followed by the reduction in tissue resistance (p = 0.01) and increase of respiratory compliance (p = 0.02). Nrf2 expression was also upregulated in the ACE2a group (p = 0.03). After transplantation, ACE2a group showed lower levels of TNF-α (p = 0.02), IL-6 (p = 0.001), IL-1ß (p = 0.01), ROS (p = 0.004) and MDA (p = 0.002), in addition to higher CAT activity (p = 0.04). In conclusion, our study suggests that ACE2 activation improves anti-inflammatory and antioxidant activity in a model of LTx.

Comparison between contact diode laser with 980 nm and 1470 nm wavelengths for posterior laryngofissure in pigs.

To compare two different wavelengths of the surgical contact diode laser (CDL) for producing a posterior laryngofissure in in-vivo pigs. Anesthetized pigs underwent a tracheostomy and an anterior laryngofissure through a cervicotomy. They were randomly selected for the CDL wavelength and Power, according to the peak of Power set at device (980nm wavelength: Ppeak power of 10 W, 15 W, and 20 W, or 1470 nm wavelength: Ppeak 3 W, 5 W, 7 W, 10 W). At the end of the experiment, the laryngotracheal specimen was extracted and sent for histology and morphometry measurements (incision size, depth, area, and lateral thermal damage). Hemodynamic data and arterial blood gases were recorded during the incisions. Statistical analysis of the comparisons between the parameters and groups had a level of significance of p < 0.05. Twenty-six pigs were divided into CDL 980 nm (n = 11) and 1470 nm (n = 15). There was a greater incision area at the thyroid level in the 980 nm CDL and a wider incision at the trachea level, with a larger distance between mucosa borders. There were no significant differences in the area of lateral thermal damage between the two groups and neither difference among the power levels tested. Both wavelengths tested showed similar results in the various combinations of power levels without significant differences in the lateral thermal damage. The posterior laryngofissure incision can be performed by either of the wavelengths at low and medium power levels without great difference on lateral thermal damage.

Exposure of cinnamyl alcohol in co-culture of BEAS-2B and dendritic cells: Interaction between CYP450 and cytokines.

The prevalence of fragrances in various hygiene products contributes to their sensorial allure. However, fragrances can induce sensitization in the skin or respiratory system, and the mechanisms involved in this process are incompletely understood. This study investigated the intricate mechanisms underlying the fragrance's effects on sensitization response, focusing on the interplay between CYP450 enzymes, a class of drug-metabolizing enzymes, and the adaptive immune system. Specifically, we assessed the expression of CYP450 enzymes and cytokine profiles in culture of BEAS-2B and mature dendritic cells (mDC) alone or in co-culture stimulated with 2 mM of a common fragrance, cinnamyl alcohol (CA) for 20 h. CYP1A1, CYP1A2, CYP1B1, CYP2A6, and CYP2A13 were analyzed by RT-PCR and IL-10, IL-12p70, IL-18, IL-33, and thymic stromal lymphopoietin (TSLP) by Cytometric Bead Array (CBA). Through RT-PCR analysis, we observed that CA increased CYP1A2 and CYP1B1 expression in BEAS-2B, with a further increased in BEAS-2B-mDC co-culture. Additionally, exposure to CA increased IL-12p70 levels in mDC rather than in BEAS-2B-mDC co-culture. In regards to IL-18, level was higher in BEAS-2B than in BEAS-2B-mDC co-culture. A positive correlation between the levels of IL-10 and CYP1B1 was found in mDC-CA-exposed and between IL-12p70 and CYP1A1 was found in BEAS-2B after CA exposure. However, IL-12p70 and CYP1A2 as well as IL-18, IL-33, and CYP1A1 levels were negative, correlated mainly in co-culture control. These correlations highlight potential immunomodulatory interactions and complex regulatory relationships. Overall, exposure to CA enhances CYP450 expression, suggesting that CA can influence immune responses by degrading ligands on xenosensitive transcription factors.

Effect of Hypertonic Saline Solution on the Ventilatory Mechanics of Lungs Donated After Brain Death.

INTRODUCTION: Brain death (BD) compromises the viability of the lung for donation. Hypertonic saline solution (HSS) induces rapid intravascular volume expansion and immunomodulatory action. We investigated its role in ventilatory mechanics (VMs) and in the inflammatory activity of the lungs of rats subjected to BD. METHODS: Wistar rats were divided into four groups: control, n = 10: intact rats subjected to extraction of the heart-lung block; BD, n = 8 (BD): rats treated with isotonic saline solution (4 mL/kg) immediately after BD; hypertonic saline 0 h, n = 9 (Hip.0'): rats treated with HSS (4 mL/kg) immediately after BD; and hypertonic saline 1 h, n = 9 (Hip.60'), rats treated with HSS (4 mL/kg) 60 min after BD. The hemodynamic characteristics, gas exchange, VMs, inflammatory mediators, and histopathological evaluation of the lung were evaluated over 240 min of BD. RESULTS: In VMs, we observed increased airway resistance, tissue resistance, tissue elastance, and respiratory system compliance in the BD group (P < 0.037), while the treated groups showed no impairment over time (P > 0.05). In the histological analysis, the BD group showed a greater area of perivascular edema and a higher neutrophil count than the control group and the Hip.60' group (P < 0.05). CONCLUSIONS: Treatment with HSS was effective in preventing changes in the elastic and resistive pulmonary components, keeping them at baseline levels. Late treatment reduced perivascular and neutrophilic edema in lung tissue.

Tacrolimus impairs airway mucociliary clearance of rats.

OBJECTIVES: Tacrolimus (TAC) is the most widely used immunosuppressive agent after lung transplantation. Considering that the ciliary beat frequency (CBF) mainly depends on the cytoplasmic calcium concentration and that TAC can affect this due to its binding with the intracellular immunophilin FKBP12, we hypothesized that TAC could also impair the airway mucociliary clearance of rats. METHODS: Sixty rats were divided into two groups (n = 30 each): Control = water; TAC = tacrolimus. After 7, 15 or 30 days of treatment, ten animals from each group were euthanized and the following parameters were studied: mucus transportability, CBF, mucociliary transport velocity (MCTV), and neutral and acid mucus production. RESULTS: There was a significant decrease in CBF (Control vs TAC: 7 days, p = 0.008; 15 days, p = 0.007; 30 days, p = 0.001) and MCTV (Control vs TAC: 7 days, p = 0.004; 15 days, p < 0.001; 30 days, p < 0.001) in all immunosuppressed animals. TAC therapy also caused an increase in acid mucus production at all treatment times (Control vs TAC: 7 days, p = 0.001; 15 days, p = 0.043; 30 days, p = 0.001). CONCLUSIONS: TAC impairs airway mucociliary clearance of rats.

Evaluation of Structural Viability of Porcine Tracheal Scaffolds after 3 and 6 Months of Storage under Three Different Protocols.

Tracheal replacement with a bioengineered tracheal substitute has been developed for long-segment tracheal diseases. The decellularized tracheal scaffold is an alternative for cell seeding. It is not defined if the storage scaffold produces changes in the scaffold's biomechanical properties. We tested three protocols for porcine tracheal scaffold preservation immersed in PBS and alcohol 70%, in the fridge and under cryopreservation. Ninety-six porcine tracheas (12 in natura, 84 decellularized) were divided into three groups (PBS, alcohol, and cryopreservation). Twelve tracheas were analyzed after three and six months. The assessment included residual DNA, cytotoxicity, collagen contents, and mechanical properties. Decellularization increased the maximum load and stress in the longitudinal axis and decreased the maximum load in the transverse axis. The decellularization of the porcine trachea produced structurally viable scaffolds, with a preserved collagen matrix suitable for further bioengineering. Despite the cyclic washings, the scaffolds remained cytotoxic. The comparison of the storage protocols (PBS at 4 °C, alcohol at 4 °C, and slow cooling cryopreservation with cryoprotectants) showed no significant differences in the amount of collagen and in the biomechanical properties of the scaffolds. Storage in PBS solution at 4 °C for six months did not change the scaffold mechanics.

A modified hydrogel production protocol to decrease cellular content.

PURPOSE: To analyze the cytotoxicity and cell in porcine-derived decellularized skin matrix. METHODS: We analyzed the effect of multiple decellularization processes by histological analysis, DNA quantification, and flow cytometry. Subsequently, we analyzed the most appropriate hydrogel concentration to minimize cytotoxicity on fibroblast culture and to maximize cell proliferation. RESULTS: After the fourth decellularization, the DNA quantification showed the lowest DNA concentration (< 50 ng/mg). Histological analysis showed no cell components in the hydrogel. Moreover, hematoxylin and eosin showed a heterogeneous structure of collagen fibers. The best hydrogel concentration ranged from 3 to 25%, and there was no significant difference between the 24 hours and seven days. CONCLUSIONS: The process of hydrogel production was effective for removing cells and DNA elements. The best hydrogel concentration ranged from 3 to 25%.

Basiliximab Does Not Impair Airway Mucociliary Clearance of Rats.

Previous studies have shown that immunosuppressive drugs impair the airway mucociliary clearance of rats. However, considering the high specificity of basiliximab (BSX) and the absence of studies reporting its side effects, our aim was to investigate whether BSX, associated or not with triple therapy, impairs the mucociliary system. Forty rats were divided into 4 groups: Control, BSX, Triple, and BSX + Triple. After 15 days of treatment, animals were euthanized and the ciliary beating frequency (CBF), mucociliary transport velocity (MCTV), neutral and acid mucin production, Muc5ac and Muc5b gene expression, inflammatory cell number, and interleukin (IL)-6 concentration were analyzed. CBF and MCTV were lower in Triple and BSX + Triple groups (p < 0.05). Neutral mucin percentage was higher in Triple group (p < 0.05), and acid mucin percentage was higher in Triple and BSX + Triple groups (p < 0.05). The Muc5ac and Muc5b gene expression was higher in Triple and BSX + Triple groups (p < 0.05). Animals from Triple and BSX + Triple groups presented fewer mononuclear cells (p < 0.05). The number of polymorphonuclear cells was higher in the Triple group (p < 0.05). In the analysis of inflammatory cells in the blood, there was a decrease in lymphocytes and an increase in neutrophils in the Triple and BSX + Triple groups (p < 0.05). The concentration of IL-6 significantly increased in the animals of the Triple and BSX + Triple groups (p < 0.05). BSX did not change the mucociliary apparatus of rats.

Airway inflammatory profile among cleaning workers from different workplaces.

BACKGROUND: Cleaning workers represent a significant proportion of the active population worldwide, with poor remuneration, particularly in developing countries. Despite this, they remain a relatively poorly studied occupational group. They are constantly exposed to agents that can cause symptoms and respiratory problems. This study aimed to evaluate upper airway inflammation in professional cleaning workers in three different occupational settings by comparing nasal cytology inflammation and clinical profiles. METHODS: We performed a cross-sectional study on the prevalence of upper airway inflammation and symptoms of asthma/rhinitis related to cleaning work, according to workplace. A total of 167 participants were divided into four groups: hospital, university, housekeeper and control. A nasal swab was collected for upper airway inflammation evaluation. Clinical profiles and respiratory symptom employee evaluations were performed using specific questionnaires (European Community Respiratory Health Survey-ECRS and the International Study of Asthma and Allergies in Childhood-ISAAC). RESULTS: Cleaning workers showed increased neutrophils and lymphocytes; the hospital and university groups showed increased macrophages compared to the housekeeper and control groups. The hospital and housekeeper groups showed increased eosinophils when they performed cleaning services for up to one year and reported having more asthma symptoms than the control group. Cleaning workers showed increased rhinitis symptoms. The university group showed increased rhinitis symptoms aggravated by the workplace compared with the hospital and housekeeper groups. Cleaning workers showed an increased affirmative response when directly asked about rhinitis symptoms compared to the control group. CONCLUSIONS: Cleaning workers showed airway inflammation, asthma symptoms and rhinitis, regardless of the occupational environment to which they were exposed, as well as showed increased rhinitis and asthma symptoms. Hospital cleaning workers showed increased macrophages, lymphocytes and eosinophils compared to the others. The length of time spent performing cleaning work was not related to nasal inflammation or respiratory symptoms in this population. However, there were differences in workplaces. Registered on ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT03311048. Registration date: 10.16.2017. Retrospectively registered.

Soluble factors of mesenchimal stem cells (FS-MSC) as a potential tool to reduce inflammation in donor's lungs after hypovolemic shock. / Fatores solúveis de células-tronco mesenquimais (FS-CTM) como uma ferramenta potencial para reduzir a inflamação nos pulmões de doadores após choque hipovolêmico.

OBJECTIVE: The shortage of viable lungs is still a major obstacle for transplantation. Trauma victims who represent potential lung donors commonly present hypovolemic shock leading to pulmonary inflammation and deterioration and rejection after transplantation. Seeking to improve lung graft, new approaches to donor treatment have been tested. This study focuses on treatment with mesenchymal stem cells (MSCs) or soluble factors produced by MSCs (FS-MSC) using a rat model for lung donors after hemorrhagic shock. METHODS: Forty-eight rats were divided into four groups: Sham (n=12), animals without induction of hypovolemic shock; Shock (n=12), animals submitted to hypovolemic shock (mean arterial pressure 40 mmHg); MSC (n=12), animals submitted to hypovolemic shock and treated with MSCs, and FS (n=12), animals submitted to hypovolemic shock and treated with FS-MSC. The animals were subjected to a 50-minute hypovolemic shock (40 mmHg) procedure. The treated animals were monitored for 115 minutes. We performed histopathology of lung tissue and quantification of inflammatory markers (TNF-α, IL-1ß, IL-6, IL-10, iCAM and vCAM) in lung tissue and peripheral blood leukocytes (PBLs). RESULTS: Hemorrhagic shock resulted in higher PBLs and neutrophil infiltrate in the lungs. FS animals had lower neutrophil density comparing with Shock and MSC animals (p<0.001). No differences in the cytokine levels in lung tissue were observed between the groups. CONCLUSIONS: The lungs of rats submitted to hemorrhagic shock and treated with FS-MSC showed reduced inflammation indicated in a decrease in lung neutrophil infiltrate.

OBJETIVO: A escassez de pulmões viáveis ainda é um grande obstáculo para o transplante. As vítimas de trauma, que constituem potenciais doadores de pulmão, comumente apresentam choque hipovolêmico que acarreta inflamação e deterioração pulmonar e rejeição após o transplante. Buscando melhorar o enxerto pulmonar, testaram-se novas abordagens ao tratamento do doador. Este estudo foca o tratamento com células-tronco mesenquimais (CTMs) ou fatores solúveis produzidos pelas CTMs (FS-CTMs), usando um modelo com ratos para doadores de pulmão após choque hemorrágico. MÉTODOS: Quarenta e oito ratos foram divididos em quatro grupos: Controle (n=12), animais sem indução de choque hipovolêmico; Choque (n=12), animais submetidos a choque hipovolêmico (pressão arterial média de 40 mmHg); CTM (n=12), animais submetidos a choque hipovolêmico e tratados com CTMs; e FS (n=12), animais submetidos a choque hipovolêmico e tratados com FS-CTMs. Os animais foram submetidos a um procedimento de choque hipovolêmico (40 mmHg) com 50 minutos de duração. Os animais tratados foram monitorados por 115 minutos. Realizamos análise histopatológica do tecido pulmonar e quantificação dos marcadores inflamatórios (TNF-α, IL-1ß, IL-6, IL-10, iCAM e vCAM) no tecido pulmonar e leucócitos no sangue periférico (LSPs). RESULTADOS: O choque hemorrágico resultou em taxas mais altas de LSPs e infiltrado de neutrófilos nos pulmões. Os animais do grupo FS apresentaram menor densidade de neutrófilos em comparação com os animais dos grupos Choque e CTM (p<0,001). Não foram observadas diferenças entre os grupos quanto aos níveis de citocinas no tecido pulmonar. CONCLUSÃO: Os pulmões dos ratos submetidos a choque hemorrágico e tratados com FS-CTM apresentaram inflamação reduzida indicada por uma diminuição do infiltrado de neutrófilos nos pulmões.

Increased bone resorption by long-term cigarette smoke exposure in animal model.

INTRODUCTION: Clinical and experimental studies have been attesting the deleterious effects of smoking mainly due to the stimulation of osteoclastogenesis and inhibition of osteoblastogenesis. However the physiological mechanisms that can explain these changes are not fully understood. AIMS: To evaluate the trabecular bone resorption effect caused by long-term exposure to cigarette smoke and the action of cytokines and reactive oxygen species involved in this process. METHODS: Sixty young adult C57BL/6 mice were allocated to two groups: control, 30 animals exposed to filtered air for 1, 3 and 6 months; and smoke, 30 animals exposed to cigarette smoke for 1, 3 and 6 months. Femoral and tibial extraction was performed to evaluate the bone mineral matrix, bone cytokines (Receptor activator of nuclear factor-kappa B ligand - RANKL and Osteoprotegerin - OPG) and oxidative stress markers (Thiobarbituric acid reactive substances - Tbars). RESULTS: Exposure to cigarette smoke (CS) generated changes in bone structural parameters in the 6th month of follow-up, demonstrating an evident bone loss; reduction in OPG/RANKL ratio from the 3rd month on and increase in Tbars in the first month, both closely related to the increase in osteoclastogenic activity and bone resorption. CONCLUSION: These findings reinforce the importance of CS-induced oxidative stress in bone compromising the bone cellular activities with a consequent impairment in bone turn over and changes in bone structure.

Decreased Bone Type I Collagen in the Early Stages of Chronic Obstructive Pulmonary Disease (COPD).

Smoking is the main risk factor for the development of chronic obstructive pulmonary disease (COPD) and is known to have deleterious effects on bone metabolism. However, the effects on bone collagen matrix during the development of COPD are unclear. The aim of this study was to evaluate the temporal effect of cigarette smoke exposure on bone type I collagen during COPD development in a cigarette smoke-induced model. C57BL/6 mice were allocated to three groups: control (C), animals exposed to filtered air for 1, 3 and 6 months; cigarette smoke (S), animals exposed to cigarette smoke for 1, 3 and 6 months; provisional smoking (PS), animals exposed to cigarette smoke for 3 months, followed by another 3 months of filtered air exposure. Evaluation of the respiratory mechanics and alveolar enlargement were performed. Femoral and tibial extraction was also performed to evaluate the type I collagen by immunofluorescence and COL1A1 gene expression. Exposure to cigarette smoke led to an alveolar enlargement and progressive reduction in lung tissue resistance and elastance, progressive reduction of type I collagen and reduction in COL1A1 gene expression. Although we did not observe any improvement in the functional and histological parameters in the provisional smoking group, we detected an increase in COL1A1 gene expression. A worsening in bone collagen matrix is part of the initial physiopathological events during COPD development and the smoking cessation induced an evident recovery of COL1A1 expression, possibly to attempt at tissue repair.

Effect of hypertonic saline in the pretreatment of lung donors with hemorrhagic shock.

BACKGROUND: Hemorrhagic shock-induced lung edema and inflammation are two of the main reasons for the rejection of lungs donated for transplantation. Hypertonic saline (HS) induces intravascular volume expansion and has considerable immunomodulating effects that might minimize edema. Our hypothesis is based on the use of a hypertonic solution for treatment of donors who are in shock in an attempt to increase the supply of lungs for transplantation. METHODS: A total of 80 rats were allocated to four groups: one group was given an infusion of normal saline (NS; n = 20), one group received HS; n = 20, a sham group (n = 20), and a Shock group (n = 20). Half of the lungs from each group were evaluated in an ex vivo perfusion system, and the other half was used for measurements of cytokine levels and neutrophil counts. RESULTS: In the ex vivo perfusion assessment, the pulmonary artery pressures of the animals in the NS and HS groups did not exhibit significant differences compared with those in the sham group (P > 0.05) but were lower than those in the Shock group (P < 0.01). Furthermore, the tumor necrosis factor-α levels and neutrophil counts were lower in the HS group than those in the Shock group (P < 0.01) and did not exhibit significant differences compared with those in either the NS and Sham groups (P > 0.05). CONCLUSIONS: We showed that HS was equivalent to isotonic saline and contributed to the treatment of lungs subjected to hemorrhagic shock.

Left ventricular chamber geometry in cardiomyopathies: insights from a computerized anatomical study.

AIMS: Some authors have hypothesized that left ventricular chamber dilatation in ischaemic and idiopathic cardiomyopathies results in spherical transformation. Aiming to characterize how this transformation occurs, a study was performed by comparing normal and dilated specimens regarding sphericity and proportionality in left heart chambers. It is important to provide data for the development of therapeutic strategies in these diseases. METHODS AND RESULTS: An anatomical study was performed by comparing normal (n = 10), ischaemic (n = 15), and idiopathic (n = 18) dilated human cardiomyopathic specimens regarding left ventricular chambers and their segmental proportionality to normal hearts. It was performed by capturing and processing images with proper software in three different levels of left ventricular chamber (basal, equatorial, and apical). These obtained data were analysed based on sphericity and proportionality by two dedicated indexes. Spherical shape: Calculated segmental indexes showed that dilated specimens were not spherical because they were smaller than as expected for a spherical shape (all values were <70% of a perfect sphere). Proportionality: There was no difference between basal index perimeters among groups, but apical index was lower in dilated specimens than in normal hearts, and so dilatation was not proportional to normal hearts. CONCLUSIONS: Left ventricular chambers of anatomical specimens with dilated cardiomyopathies did not display a spherical shape and were not proportional to normal hearts.

Human bronchial epithelial cells exposed in vitro to diesel exhaust particles exhibit alterations in cell rheology and cytotoxicity associated with decrease in antioxidant defenses and imbalance in pro- and anti-apoptotic gene expression.

Diesel exhaust particles (DEPs) from diesel engines produce adverse alterations in cells of the airways by activating intracellular signaling pathways and apoptotic gene overexpression, and also by influencing metabolism and cytoskeleton changes. This study used human bronchial epithelium cells (BEAS-2B) in culture and evaluates their exposure to DEPs (15ug/mL for 1 and 2 h) in order to determine changes to cell rheology (viscoelasticity) and gene expression of the enzymes involved in oxidative stress, apoptosis, and cytotoxicity. BEAS-2B cells exposed to DEPs were found to have a significant loss in stiffness, membrane stability, and mitochondrial activity. The genes involved in apoptosis [B cell lymphoma 2 (BCL-2 and caspase-3)] presented inversely proportional expressions (p = 0.05, p = 0.01, respectively), low expression of the genes involved in antioxidant responses [SOD1 (superoxide dismutase 1); SOD2 (superoxide dismutase 2), and GPx (glutathione peroxidase) (p = 0.01)], along with an increase in cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) (p = 0.01). These results suggest that alterations in cell rheology and cytotoxicity could be associated with oxidative stress and imbalance between pro- and anti-apoptotic genes.

Alternative solution for ex vivo lung perfusion, experimental study on donated human lungs non-accepted for transplantation.

PURPOSE: To evaluate a new perfusate solution to be used for ex vivo lung perfusion. METHODS: Randomized experimental study using lungs from rejected brain-dead donors harvested and submitted to 1 hour of ex vivo lung perfusion (EVLP) using mainstream solution or the alternative. RESULTS: From 16 lungs blocs tested, we found no difference on weight after EVLP: Steen group (SG) = 1,097±526g; Alternative Perfusion Solution (APS) = 743±248g, p=0.163. Edema formation, assessed by Wet/dry weigh ratio, was statistically higher on the Alternative Perfusion Solution group (APS = 3.63 ± 1.26; SG = 2.06 ± 0.28; p = 0.009). No difference on PaO2 after EVLP (SG = 498±37.53mmHg; APS = 521±55.43mmHg, p=0.348, nor on histological analyses: pulmonary injury score: SG = 4.38±1.51; APS = 4.50±1.77, p=0.881; apoptotic cells count after perfusion: SG = 2.4 ± 2.0 cells/mm2; APS = 4.8 ± 6.9 cells/mm2; p = 0.361). CONCLUSION: The ex vivo lung perfusion using the alternative perfusion solution showed no functional or histological differences, except for a higher edema formation, from the EVLP using Steen Solution(r) on lungs from rejected brain-dead donors.

Alternative solution for ex vivo lung perfusion, experimental study on donated human lungs non-accepted for transplantation

PURPOSE: To evaluate a new perfusate solution to be used for ex vivo lung perfusion. METHODS: Randomized experimental study using lungs from rejected brain-dead donors harvested and submitted to 1 hour of ex vivo lung perfusion (EVLP) using mainstream solution or the alternative. RESULTS: From 16 lungs blocs tested, we found no difference on weight after EVLP: Steen group (SG) = 1,097±526g; Alternative Perfusion Solution (APS) = 743±248g, p=0.163. Edema formation, assessed by Wet/dry weigh ratio, was statistically higher on the Alternative Perfusion Solution group (APS = 3.63 ± 1.26; SG = 2.06 ± 0.28; p = 0.009). No difference on PaO2 after EVLP (SG = 498±37.53mmHg; APS = 521±55.43mmHg, p=0.348, nor on histological analyses: pulmonary injury score: SG = 4.38±1.51; APS = 4.50±1.77, p=0.881; apoptotic cells count after perfusion: SG = 2.4 ± 2.0 cells/mm2; APS = 4.8 ± 6.9 cells/mm2; p = 0.361). CONCLUSION: The ex vivo lung perfusion using the alternative perfusion solution showed no functional or histological differences, except for a higher edema formation, from the EVLP using Steen Solution(r) on lungs from rejected brain-dead donors. .

Nova contribuição ao estudo do remodelamento ventricular e dos anéis valvares na cardiomiopatia dilatada: avaliação anátomo-histopatológica / New contribution to the study of ventricular remodeling and valve rings in dilated cardiomyopathy: anatomical and histological evaluation

Introdução: A cardiomiopatia dilatada idiopática (CMDId) é causadora de grande impacto, porém aspectos de sua fisiopatologia são desconhecidos. Objetivo: Avaliar aspectos anatomo-histológicos de corações com CMDId comparando-os a corações normais, com medidas perimetrais dos anéis atrioventriculares direito (AVD) e esquerdo (AVE) e dos ventrículos direito (VD) e esquerdo (VE) e a porcentagem de fibras colágenas e elásticas dos anéis. Métodos: Foram avaliados 13 corações de cadáveres portadores de CMDId e 13 corações normais, que foram dissecados mantendo-se os anéis atrioventriculares e a massa ventricular, com laminação em segmentos correspondentes a 20%, 50% e 80% da distância entre o sulco atrioventricular e o ápice ventricular. Os cortes foram submetidos à digitalização fotográfica, sendo comparadas as medidas. Os anéis foram dissecados, medidos e enviados ao laboratório de anatomia patológica, sendo realizadas colorações por meio de hematoxilina-eosina, picrossírius e resorcina fuccina oxidada. Resultados: Com relação aos ventrículos, no grupo CMDId ocorre dilatação nos segmentos apical, equatorial e basal. A medida do AVD foi maior no grupo CMDId, não havendo diferença no AVE entre os grupos. Com relação ao percentual de fibras colágenas, há diminuição no grupo CMDId em relação ao grupo normal. Com relação às fibras elásticas, não houve diferença entre os grupos. Conclusão: Ocorre alteração da geometria ventricular com dilatação no grupo CMDId. Na CMDId observou-se aumento no perímetro do AVD. Não se observou aumento do perímetro do AVE. Houve diminuição percentual na área total de colágeno tanto no AVD quanto no AVE em corações com CMDId. .

Introduction: Idiopathic dilated cardiomyopathy causes great impact but many aspects of its pathophysiology remain unknown. Objective: To evaluate anatomical and histological aspects of hearts with idiopathic dilated cardiomyopathy and compare them to a control group, evaluating the behavior of the perimeters of the atrioventricular rings and ventricles and to compare the percentage of collagen and elastic fibers of the atrioventricular rings. Methods: Thirteen hearts with cardiomyopathy and 13 normal hearts were analysed. They were dissected keeping the ventricular mass and atrioventricular rings, with lamination of segments 20%, 50% and 80% of the distance between the atrioventricular groove and the ventricular apex. The sections were subjected to photo scanning, with measurement of perimeters. The atrioventricular rings were dissected and measured digitally to evaluate their perimeters, later being sent to the pathology laboratory, and stained by hematoxylin-eosin, picrosirius and oxidized resorcin fuccin. Results: Regarding to ventricles, dilation occurs in all segments in the pathological group, and the right atrioventricular ring measurement was higher in idiopathic dilated cardiomyopathy group, with no difference in the left side. With respect to collagen, both sides had lower percentage of fibers in the pathological group. With respect to the elastic fibers, there was no difference between the groups. Conclusion: There is a change in ventricular geometry in cardiomyopathy group. The left atrioventricular ring does not dilate, in spite of the fact that in both ventricles there is lowering of collagen. .

Idiopathic dilated cardiomyopathy: computerized anatomic study of relashionship between septal and free left ventricle wall.

INTRODUCTION: A feature of dilated cardiomyopathy is the deformation of ventricular cavity, which contributes to systolic dysfunction. Few studies have evaluated this deformation bearing in mind ventricular regions and segments of the ventricle, which could reveal important details of the remodeling process, supporting a better understanding of its role in functional impairment and the development of new therapeutic strategies. OBJECTIVE: To evaluate if, in basal, equatorial and apical regions, increased internal transverse perimeter of left ventricle in idiopathic dilated cardiomyopathy occurs proportionally between the septal and non-septal segment. METHODS: We performed an anatomical study with 28 adult hearts from human cadavers. One group consisted of 18 hearts with idiopathic dilated cardiomyopathy and another group with 10 normal hearts. After lamination and left ventricle digital image capture, in three different regions (base, equator and apex), the transversal internal perimeter of left ventricle was divided into two segments: septal and not septal. These segments were measured by proper software. It was established an index of proportionality between these segments, called septal and non-septal segment index. Then we determined whether this index was the same in both groups. RESULTS: Among patients with normal hearts and idiopathic dilated cardiomyopathy, the index of proportionality between the two segments (septal and non-septal) showed no significant difference in the three regions analyzed. The comparison results of the indices NSS/SS among normal and enlarged hearts were respectively: in base 1.99 versus 1.86 (P=0.46), in equator 2.22 versus 2.18 (P=0.79) and in apex 2.96 versus 3.56 (P=0.11). CONCLUSION: In the idiopathic dilated cardiomyopathy, the transversal dilatation of left ventricular internal perimeter occurs proportionally between the segments corresponding to the septum and free wall at the basal, equatorial and apical regions of this chamber.

Idiopathic dilated cardiomyopathy: computerized anatomic study of relashionship between septal and free left ventricle wall / Cardiomiopatia dilatada idiopática: estudo anatômico computadorizado da relação entre o septo e a parede livre do ventrículo esquerdo

Introduction: A feature of dilated cardiomyopathy is the deformation of ventricular cavity, which contributes to systolic dysfunction. Few studies have evaluated this deformation bearing in mind ventricular regions and segments of the ventricle, which could reveal important details of the remodeling process, supporting a better understanding of its role in functional impairment and the development of new therapeutic strategies. Objective: To evaluate if, in basal, equatorial and apical regions, increased internal transverse perimeter of left ventricle in idiopathic dilated cardiomyopathy occurs proportionally between the septal and non-septal segment. Methods: We performed an anatomical study with 28 adult hearts from human cadavers. One group consisted of 18 hearts with idiopathic dilated cardiomyopathy and another group with 10 normal hearts. After lamination and left ventricle digital image capture, in three different regions (base, equator and apex), the transversal internal perimeter of left ventricle was divided into two segments: septal and not septal. These segments were measured by proper software. It was established an index of proportionality between these segments, called septal and non-septal segment index. Then we determined whether this index was the same in both groups. Results: Among patients with normal hearts and idiopathic dilated cardiomyopathy, the index of proportionality between the two segments (septal and non-septal) showed no significant difference in the three regions analyzed. The comparison results of the indices NSS/SS among normal and enlarged hearts were respectively: in base 1.99 versus 1.86 (P=0.46), in equator 2.22 versus 2.18 (P=0.79) and in apex 2.96 versus 3.56 (P=0.11). Conclusion: In the idiopathic dilated cardiomyopathy, the transversal dilatation of left ventricular internal perimeter occurs proportionally between the segments corresponding to the septum and free wall at the ...

Introdução: Uma das características da cardiomiopatia dilatada idiopática é a deformação da cavidade ventricular, a qual contribui para a disfunção sistólica. Poucos trabalhos julgam importante a avaliação dessa deformação ventricular levando em consideração regiões e segmentos do ventrículo, o que pode revelar detalhes importantes do processo de remodelamento, dando suporte a um melhor entendimento do seu papel no comprometimento funcional e ao surgimento de novas estratégias terapêuticas. Objetivo: Verificar se, em regiões diferentes, o aumento do perímetro transversal da câmara ventricular esquerda na cardiomiopatia dilatada idiopática ocorre de maneira proporcional entre o segmento septal e o não septal (parede livre). Métodos: Foi realizado um estudo anatômico com 28 corações adultos. Um grupo foi constituído por 18 corações com cardiomiopatia dilatada idiopática e outro grupo com 10 corações normais. Em três regiões diferentes (base, equador e ápice), o perímetro interno transversal do ventrículo esquerdo foi dividido em dois segmentos: septal e não septal. Foi criado um índice de proporcionalidade entre esses segmentos. Em seguida verificou-se se esse índice era o mesmo entre os grupos. Resultados: Entre corações normais e portadores de cardiomiopatia dilatada idiopática, o índice de proporcionalidade entre os dois segmentos (septal e não septal) não apresentou diferença significativa nas três regiões analisadas. Conclusão: Na cardiomiopatia dilatada idiopática, a dilatação transversal do septo é proporcional à dilatação da parede livre nas regiões basal, equatorial e apical da câmara ventricular esquerda. .