Irreversible Fibrosis Research Articles

Left ventricular lobal longitudinal strain as a prognostic marker in low-risk patients undergoing TAVI

Abstract Funding Acknowledgements Type of funding sources: None. Background Left ventricular global longitudinal strain (LV GLS) correlate with the risk of symptoms, irreversible myocardial damage and progressive myocardial fibrosis. LV GLS detects subtle changes in LV function that precede those of LVEF and is associated to outcomes after TAVI. Purpose Evaluation of the LV GLS as the prognostic parameter in patients low-, intermediate and high-risk patients undergoing TAVI and its potential relationship with frailty syndrom. Methods The study included 105 patients (mean age 82.36 ± 4.5) with severe AS treated with TAVI at the Department of Invasive Cardiology, Central Clinical Hospital of the Ministry of Interior in Warsaw. Each patient had laboratory tests, ECG, echocardiography (LV GLS) and was assessed based on the STS scale and the Katz frailty scale. Follow-up observations were carried out at 1 month and 1 year. Results In the study population 46% were men, the mean age was 82.36 ± 4.5 years, the mean STS score was 7.03 ± 4.24. The mean pre-TAVI LVEF was 54.51 ± 6.44% (in 87 (82.8%) patients above 50%). The mean LV GLS before TAVI was -12.82 ± 1.94%. AVAI area was 0.38 ± 0.08 cm/m2, and the mean gradient through the stenotic aortic valve was 51.69 ± 10.66 mmHg. LV GLS was significantly improved in patients after TAVI. LV GLS analysis showed change from -12.82% before TAVI, to -14.35% after 1-month follow-up and -14.47% at 1-year follow-up (p ≤ 0,05, p ≤ 0,05 respectively). LV GLS of -11% was a cut-off value determining the risk of death after 1 year post-TAVI (p < 0,001). The area under the curve was 0,87, which was a statistically significant result that can be used as a significant prognostic factor. In low-risk patients there was a significant improvement of LV GLS in 1-year follow-up, compared to patients with STS 4-8% (p ≤ 0.01) and in patients with STS> 8% (p ≤ 0, 05) (Tab. 1). Logistic regression analysis showed that the change of LV GLS at 1 year significantly correlated with Katz frailty score at 1-month and 1-year follow-up ((p ≤ 0,01, p ≤ 0,01 respectively) (Tab. 2). Conclusion LV GLS of -11% was a cut-off value distinguishing patients with increased risk of death after TAVI. In low-risk patients the improvement in LV GLS indicates a favorable reverse myocardial remodeling after TAVI and better prognosis after TAVI, which was not observed in the intermediate- and high-risk patients. Abstract Figure. Abstract Figure.

Brazilian initial experience with lung transplantation due to irreversible lung fibrosis post-COVID-19 in a national reference center: a cohort study.

Lung transplantation (LTx) has been discussed as an option for treating irreversible lung fibrosis post-coronavirus disease 2019 (COVID-19), in selected cases. To report on the initial experience and management of end-stage lung disease due to COVID-19 at a national center reference in Brazil. Cohort study conducted at a national reference center for lung transplantation. Medical charts were reviewed regarding patients' demographics and pre-COVID-19 characteristics, post-LTx due to COVID-19. Between March 2020 and September 2021, there were 33 cases of LTx. During this period, we evaluated 11 cases of severe COVID-19-related acute respiratory distress syndrome (ARDS) that were potentially candidates for LTx. Among these, LTx was only indicated for three patients (9.1%). All of these patients were on venovenous extracorporeal membrane oxygenation (ECMO), and the procedure that they underwent was central venoarterial ECMO. All three patients were still alive after the first 30 postoperative days. However, patient #1 and patient #2 subsequently died due to fungal sepsis on the 47th and 52nd postoperative days, respectively. Patient #3 was discharged on the 30th postoperative day. LTx is feasible among these complex patients. Survival over the first 30 days was 100%, and this favors surgical feasibility. Nonetheless, these were critically ill patients.

POS-379 TO INVESTIGATE THE EFFECT OF HERBA LYSIMACHIAE IN THE TREATMENT OF OBSTRUCTIVE NEPHROPATHY BASED ON STAT-1/TREM-1 PATHWAY

Obstructive nephropathy is a major cause of chronic renal failure in children and adults.Clinical and animal experiments have found that renal damage still exists after obstruction is relieved, which is mainly related to irreversible fibrosis changes caused by persistent inflammatory infiltration, and there is no specific medicine for western medicine treatment. Herba lysimachiae can detoxify detumescence, diuresis tonglin, has a certain kidney protection. However, there is still a lack of systematic knowledge about the herba lysimachiae components and mechanism of s. chinensis in the treatment of obstructive nephropathy. Twenty SD rats were randomly divided into Sham operation group (Sham), unilateral ureteral obstruction operation group (UUO), Pennyswort intervention Sham operation group (Sham+Lys), herba lysimachiae intervention model group (UUO+ Lys).From the 1st day after surgery, the decoction of herba lysimachiae was given 24g/kg, once a day, for continuous 2w.Or intragastric administration of normal saline at the same time.Routine biochemical kit was used to detect renal function 2 weeks later.Renal tubule dilatation, mesangial hyperplasia and renal interstitial fibrosis were detected by HE, PAS and Masson staining.Immunohistochemistry and immunofluorescence were used to detect the activation of STAT-1/ TreM-1 pathway, macrophage aggregation (CD68+ iNOS+), renal tubular injury markers (KIM-1), and fibrosis related molecules (α-SMA, TGF-beta) in renal tissues. In the model group, the renal tubules were oppressed by urine retention on the obstructed side. Pathological staining showed that the epithelial cells of the renal tubules were necrotic to varying degrees, and the interstitial was infiltrated by acute and chronic inflammatory cells. Some of the necrotic renal tubules were gradually replaced by fibrous scar, and the formation of renal interstitial fibrosis was visible.Biochemical tests showed that the creatinine and renal injury scores were significantly higher than those of the normal group.Immunohistochemistry/immunofluorescence assay showed increased stat-1 /TREM-1 expression.Abnormal aggregation of M1-type macrophages in renal interstitium, accompanied by renal injury and fibrosis, showed increased expressions of KIM-1, α-SMA and TGF-beta (all P<0.05).In contrast, stat-1 /TREM-1 expression was decreased in renal tissue after herba lysimachiae intervention, and the above inflammatory and fibrosis related indicators were improved (P<0.05). Herba lysimachiae can protect renal function and inhibit renal inflammation and fibrosis in UUO rats, and this mechanism is related to the STAT-1/TREM-1 pathway.

Inflammogenic effect of polyacrylic acid in rat lung following intratracheal instillation

BackgroundSome organic chemicals are known to cause allergic disorders such as bronchial asthma and hypersensitivity pneumonitis, and it has been considered that they do not cause irreversible pulmonary fibrosis. It has recently been reported, however, that cross-linked acrylic acid-based polymer, an organic chemical, might cause serious interstitial lung diseases, including pulmonary fibrosis. We investigated whether or not intratracheal instillation exposure to cross-linked polyacrylic acid (CL-PAA) can cause lung disorder in rats.MethodsMale F344 rats were intratracheally instilled with dispersed CL-PAA at low (0.2 mg/rat) and high (1.0 mg/rat) doses, and were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months after exposure to examine inflammatory and fibrotic responses and related gene expressions in the lungs. Rat lungs exposed to crystalline silica, asbestos (chrysotile), and NiO and CeO2 nanoparticles were used as comparators.ResultsPersistent increases in total cell count, neutrophil count and neutrophil percentage, and in the concentration of the cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2 and C-X-C motif chemokine 5 (CXCL5), which correlated with lung tissue gene expression, were observed in bronchoalveolar lavage fluid (BALF) from 3 days until at least 1 month following CL-PAA intratracheal instillation. Persistent increases in heme oxygenase-1 (HO-1) in the lung tissue were also observed from 3 days to 6 months after exposure. Histopathological findings of the lungs demonstrated that extensive inflammation at 3 days was greater than that in exposure to silica, NiO nanoparticles and CeO2 nanoparticles, and equal to or greater than that in asbestos (chrysotile) exposure, and the inflammation continued until 1 month. Fibrotic changes also progressed after 1 month postexposure.ConclusionOur results suggested that CL-PAA potentially causes strong neutrophil inflammation in the rat and human lung.

Lung Ultrasound as a First-Line Test in the Evaluation of Post-COVID-19 Pulmonary Sequelae.

Background: Interstitial lung sequelae are increasingly being reported in survivors of COVID-19 pneumonia. An early detection of these lesions may help prevent the development of irreversible lung fibrosis. Lung ultrasound (LUS) has shown high diagnostic accuracy in interstitial lung disease (ILD) and could likely be used as a first-line test for post-COVID-19 lung sequelae.Methods: Single-center observational prospective study. Follow-up assessments of consecutive patients hospitalized for COVID-19 pneumonia were conducted 2–5 months after the hospitalization. All patients underwent pulmonary function tests (PFTs), high-resolution computed tomography (HRCT), and LUS. Radiological alterations in HRCT were quantified using the Warrick score. The LUS score was obtained by evaluating the presence of pathological B-lines in 12 thoracic areas (range, 0–12). The correlation between the LUS and Warrick scores was analyzed.Results: Three hundred and fifty-two patients who recovered from COVID-19 pneumonia were recruited between July and September 2020. At follow-up, dyspnea was the most frequent symptom (69.3%). FVC and DLCO alterations were present in 79 (22.4%) and 234 (66.5%) patients, respectively. HRCT showed relevant interstitial lung sequelae (RILS) in 154 (43.8%) patients (Warrick score ≥ 7). The LUS score was strongly correlated with the HRCT Warrick score (r = 0.77) and showed a moderate inverse correlation with DLCO (r = −0.55). The ROC curve analysis revealed that a LUS score ≥ 3 indicated an excellent ability to discriminate patients with RILS (sensitivity, 94.2%; specificity, 81.8%; negative predictive value, 94.7%).Conclusions: LUS could be implemented as a first-line procedure in the evaluation of Post-COVID-19 interstitial lung sequelae. A normal LUS examination rules out the presence of these sequelae in COVID-19 survivors, avoiding the need for additional diagnostic tests such as HRCT.

Endoscopic Ultrasonography in Children with Eosinophilic Esophagitis-A Review.

Endoscopic ultrasonography (EUS) is a diagnostic endoscopy of the upper gastrointestinal tract, during which ultrasound of nearby organs is also performed. It is also possible to perform a fine needle aspiration biopsy. Currently, EUS is performed more frequently in adults. Despite some limitations, this diagnostic method is also more and more often performed in pediatric patients. Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus, which also occurs in children, and leads to irreversible fibrosis of the esophagus wall, if left untreated. Traditional methods of diagnosing and monitoring EoE treatment have significant limitations, and the use of EUS and total esophageal wall thickness (TWT) assessment may bring measurable benefits. Several studies have shown an increased thickening of TWT in EoE in children compared to pediatric patients with gastroesophageal reflux disease, and a decrease in TWT in adults who responded to EoE treatment. These results suggest that EUS and TWT measurement may become an important test in diagnostics, monitoring the effectiveness of therapy, assessing disease progression, and in individualizing the method and duration of EoE treatment also in children.

A Unique Interaction of Methotrexate and Nitrofurantoin Resulting in Irreversible Pulmonary Fibrosis

Pulmonary toxicity is the most well-known severe complication related to both methotrexate and nitrofurantoin, which can present as acute, subacute, and chronic. Rheumatoid arthritis is also known to cause pulmonary disease if left untreated. In this report, we present a unique case of a 94-year-old female being treated with methotrexate for several years and then treated with nitrofurantoin in the setting of rheumatoid arthritis and chronic urinary tract infections, resulting in irreversible pulmonary fibrosis, which can further cause more susceptibility to infections and pneumonia. Drug-drug interactions are common in polypharmacy and a patient's history should be analyzed thoroughly before prescribing any new medication that can cause more harm to the patient than good.

Irreversibility of Pulmonary Fibrosis.

Pulmonary fibrosis, a kind of terminal pathological changes in the lung, is caused by aberrant wound healing, deposition of extracellular matrix (ECM), and eventually replacement of lung parenchyma by ECM. Pulmonary fibrosis induced by acute lung injury and some diseases is reversible under treatment. While idiopathic pulmonary fibrosis is persistent and irreversible even after treatment. Currently, the pathogenesis of irreversible pulmonary fibrosis is not fully elucidated. The known factors associated with the development of irreversible fibrosis include apoptosis resistance of (myo)fibroblasts, dysfunction of pulmonary vessel, cell mitochondria and autophagy, aberrant epithelia hyperplasia and lipid metabolism disorder. In this review, other than a brief introduction of reversible pulmonary fibrosis, we focus on the underlying pathogenesis of irreversible pulmonary fibrosis from the above aspects as well as preclinical disease models, and also suggest directions for future studies.

Surgery versus Medical Therapy in Luminal Ileocecal Crohn's Disease.

The deeper understanding of the inflammatory process which gradually evolves into irreversible fibrosis and tissue damage has provided a precise picture of the disease course of luminal ileocecal Crohn's disease. According to the model of progressive structural damage, ideal time windows for medical and surgical treatment have been identified. While complicated disease clearly profits from surgical treatment, uncomplicated disease has become, in the last years, the most debatable setting in terms of different approaches including early surgery. On one hand, the rationale of traditional escalating medical therapy (step-up approach) has been undermined by the top-down medical approach. Indeed, the step-up approach has the possible drawback of delaying, up to a later disease stage, the use of more effective agents such as anti-tumor necrosis factors. Conversely, the top-down approach might expose patients to an overtreatment along with side effects including hypersensitivity to biologic agents. More recently, it has been shown how early surgery could be a valid option in this subset of patients being more cost-effective than medical therapy. Involving the surgeon at an early stage is considered now a good clinical practice and, in this scenario full of possibilities, the surgeon should be included into the decision-making process from the very beginning of patient management.

Reversible Bronchiectasis in COVID-19 Survivors With Acute Respiratory Distress Syndrome: Pseudobronchiectasis.

To retrospectively analyze whether traction bronchiectasis was reversible in coronavirus disease 2019 (COVID-19) survivors with acute respiratory distress syndrome (ARDS), and whether computed tomography (CT) findings were associated with the reversibility, 41 COVID-19 survivors with ARDS were followed-up for more than 4 months. Demographics, clinical data, and all chest CT images were collected. The follow-up CT images were compared with the previous CT scans. There were 28 (68%) patients with traction bronchiectasis (Group I) and 13 (32%) patients without traction bronchiectasis (Group II) on CT images. Traction bronchiectasis disappeared completely in 21 of the 28 (75%) patients (Group IA), but did not completely disappear in seven of the 28 (25%) patients (Group IB). In the second week after onset, the evaluation score on CT images in Group I was significantly higher than that in Group II (p = 0.001). The proportion of reticulation on the last CT images in Group IB was found higher than that in Group IA (p < 0.05). COVID-19 survivors with ARDS might develop traction bronchiectasis, which can be absorbed completely in most patients. Traction bronchiectasis in a few patients did not disappear completely, but bronchiectasis was significantly relieved. The long-term follow-up is necessary to further assess whether traction bronchiectasis represents irreversible fibrosis.

Cabozantinib ameliorates lipopolysaccharide-induced lung inflammation and bleomycin--induced early pulmonary fibrosis in mice

The lung, as the primary organ for gas exchange in mammals, is the main target organ for many pathogens and allergens, which may cause acute lung injury. A certain proportion of acute lung injury may progress into irreversible pulmonary fibrosis. Both acute lung injury and pulmonary fibrosis have high mortality rates and few effective treatments. Cabozantinib is a multi-target small molecule tyrosine kinase inhibitor and has been approved for the treatment of multiple malignant solid tumors. In this study, we explored the role of cabozantinib in acute lung injury and pulmonary fibrosis in vivo and in vitro. In the lipopolysaccharide and bleomycin induced mouse lung injury models, cabozantinib significantly improved the pathological state and reduced the infiltration of inflammatory cells in the lung tissues. In the bleomycin induced pulmonary fibrosis model, cabozantinib significantly reduced the area of pulmonary fibrosis and improved lung function in mice. The results of in vitro studies showed that cabozantinib could inhibit the inflammatory response and apoptosis of alveolar epithelial cells by inhibiting the activation of TLR4/NF-κB and NLRP3 inflammasome pathways. At the same time, cabozantinib could inhibit the activation of lung fibroblasts through suppressing the TGF-β1/Smad pathway, and promote the apoptosis of fibroblasts. In summary, cabozantinib could alleviate lung injury through regulating the TLR4 /NF-κB/NLRP3 inflammasome pathway, and alleviate pulmonary fibrosis by inhibiting the TGF-β1/Smad3 signaling pathway.

The effects of inhaling hydrogen gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced lung injury

BackgroundAcute respiratory distress syndrome, which is caused by acute lung injury, is a destructive respiratory disorder caused by a systemic inflammatory response. Persistent inflammation results in irreversible alveolar fibrosis. Because hydrogen gas possesses anti-inflammatory properties, we hypothesized that daily repeated inhalation of hydrogen gas could suppress persistent lung inflammation by inducing functional changes in macrophages, and consequently inhibit lung fibrosis during late-phase lung injury.MethodsTo test this hypothesis, lung injury was induced in mice by intratracheal administration of bleomycin (1.0 mg/kg). Mice were exposed to control gas (air) or hydrogen (3.2% in air) for 6 h every day for 7 or 21 days. Respiratory physiology, tissue pathology, markers of inflammation, and macrophage phenotypes were examined.ResultsMice with bleomycin-induced lung injury that received daily hydrogen therapy for 21 days (BH group) exhibited higher static compliance (0.056 mL/cmH2O, 95% CI 0.047–0.064) than mice with bleomycin-induced lung injury exposed only to air (BA group; 0.042 mL/cmH2O, 95% CI 0.031–0.053, p = 0.02) and lower static elastance (BH 18.8 cmH2O/mL, [95% CI 15.4–22.2] vs. BA 26.7 cmH2O/mL [95% CI 19.6–33.8], p = 0.02). When the mRNA levels of pro-inflammatory cytokines were examined 7 days after bleomycin administration, interleukin (IL)-6, IL-4 and IL-13 were significantly lower in the BH group than in the BA group. There were significantly fewer M2-biased macrophages in the alveolar interstitium of the BH group than in the BA group (3.1% [95% CI 1.6–4.5%] vs. 1.1% [95% CI 0.3–1.8%], p = 0.008).ConclusionsThe results suggest that hydrogen inhalation inhibits the deterioration of respiratory physiological function and alveolar fibrosis in this model of lung injury.

Evaluation of the long-term effect of polyhexamethylene guanidine phosphate in a rat lung model using conventional chest computed tomography with histopathologic analysis.

There have been no studies on the effects of polyhexamethylene guanidine phosphate (PHMG) after a long period of exposure in the rodent model. We aimed to evaluate long-term lung damage after PHMG exposure using conventional chest computed tomography (CT) and histopathologic analysis in a rat model. A PHMG solution was intratracheally administrated to 24 male rats. At 8, 26, and 52 weeks after PHMG instillation, conventional chest CT was performed in all rats and both lungs were extracted for histopathologic evaluation. At 52 weeks after PHMG instillation, four carcinomas had developed in three of the eight rats (37.5%). Bronchiolo-alveolar hyperplasia and adenoma were found in rats at 8, 26, and 52 weeks post-instillation. The number of bronchiolo-alveolar hyperplasia significantly increased over time (P-value for trend< 0.001). The severity of lung fibrosis and fibrosis scores significantly increased over time (P-values for trend = 0.002 and 0.023, respectively). Conventional chest CT analysis showed that bronchiectasis and linear density scores suggestive of fibrosis significantly increased over time (P-value for trend < 0.001). Our study revealed that one instillation of PHMG in a rat model resulted in lung carcinomas and progressive and irreversible fibrosis one year later based on conventional chest CT and histopathologic analysis. PHMG may be a lung carcinogen in the rat model.

PD45-10 CELL-BASED MOLECULAR THERAPY FOR CHRONIC KIDNEY TUBULOINTERSTITIAL FIBROSIS

INTRODUCTION AND OBJECTIVE:Chronic, irreversible tubulointerstitial fibrosis (TIF) is a common final pathway leading to end stage kidney disease. There is no effective cure; however, cell-based mol...

A comprehensive framework for navigating patient care in systemic sclerosis: A global response to the need for improving the practice of diagnostic and preventive strategies in SSc.

Systemic sclerosis (SSc), the most lethal of rheumatologic conditions, is the cause of death in >50% of SSc cases, led by pulmonary fibrosis followed by pulmonary hypertension and then scleroderma renal crisis (SRC). Multiple other preventable and treatable SSc-related vascular, cardiac, gastrointestinal, nutritional and musculoskeletal complications can lead to disability and death. Vascular injury with subsequent inflammation transforming to irreversible fibrosis and permanent damage characterizes SSc. Organ involvement is often present early in the disease course of SSc, but requires careful history-taking and vigilance in screening to detect. Inflammation is potentially reversible provided that treatment intensity quells inflammation and other immune mechanisms. In any SSc phenotype, opportunities for early treatment are prone to be under-utilized, especially in slowly progressive phenotypes that, in contrast to severe progressive ILD, indolently accrue irreversible organ damage resulting in later-stage life-limiting complications such as pulmonary hypertension, cardiac involvement, and malnutrition. A single SSc patient visit often requires much more physician and staff time, organization, vigilance, and direct management for multiple organ systems compared to other rheumatic or pulmonary diseases. Efficiency and efficacy of comprehensive SSc care enlists trending of symptoms and bio-data. Financial sustainability of SSc care benefits from understanding insurance reimbursement and health system allocation policies for complex patients. Sharing care between recognised SSc centers and local cardiology/pulmonary/rheumatology/gastroenterology colleagues may prevent complications and poor outcomes, while providing support to local specialists. As scleroderma specialists, we offer a practical framework with tools to facilitate an optimal, comprehensive and sustainable approach to SSc care. Improved health outcomes in SSc relies upon recogntion, management and, to the extent possible, prevention of SSc and treatment-related complications.

Place of bronchoscopy in the diagnostics and follow-up of patients with idiopathic pulmonary hemosiderosis

The idiopathic pulmonary hemosiderosis is a rare, life-threatening condition observed mainly in children and characterized by recurrent episodes of diffuse alveolar hemorrhages. The disease is characterized by the triad of hemoptysis, alveolar infiltrates in chest radiography, and iron-deficiency anemia. The recurrent episodes of alveolar hemorrhage can lead to chronic iron-deficiency anemia and irreversible pulmonary fibrosis; therefore, early diagnosis and treatment are crucial to the outcome of the disease.The idiopathic pulmonary hemosiderosis is a rare, life-threatening condition observed mainly in children and characterized by recurrent episodes of diffuse alveolar hemorrhages. The disease is characterized by the triad of hemoptysis, alveolar infiltrates in chest radiography, and iron-deficiency anemia. The recurrent episodes of alveolar hemorrhage can lead to chronic iron-deficiency anemia and irreversible pulmonary fibrosis; therefore, early diagnosis and treatment are crucial to the outcome of the disease.

Lung Transplantation for End-Stage Respiratory Failure After Severe COVID-19: A Report of 2 Cases

We report 2 cases of bilateral lung transplantation for nonresolving coronavirus disease 2019 associated respiratory failure. In the first patient, the severe acute respiratory syndrome coronavirus 2 infection caused acute respiratory distress syndrome requiring prolonged extracorporeal membrane oxygenation support; in the second patient, coronavirus disease 2019 resulted in irreversible pulmonary fibrosis requiring only ventilatory support. The 2 cases represent the 2 ends of the spectrum showing significant differences in preoperative and postoperative courses.

Chiari Malformation: An Unhelpful Eponym

We report 2 cases of bilateral lung transplantation for nonresolving coronavirus disease 2019 associated respiratory failure. In the first patient, the severe acute respiratory syndrome coronavirus 2 infection caused acute respiratory distress syndrome requiring prolonged extracorporeal membrane oxygenation support; in the second patient, coronavirus disease 2019 resulted in irreversible pulmonary fibrosis requiring only ventilatory support. The 2 cases represent the 2 ends of the spectrum showing significant differences in preoperative and postoperative courses.

Resolvin-D1 attenuation of angiotensin II-induced cardiac inflammation in mice is associated with prevention of cardiac remodeling and hypertension

AimsDespite the broad pharmacological arsenal to treat hypertension, chronic patients may develop irreversible cardiac remodeling and fibrosis. Angiotensin II, the main peptide responsible for the Renin-Angiotensin-Aldosterone-System, has been closely linked to cardiac remodeling, hypertrophy, fibrosis, and hypertension, and some of these effects are induced by inflammatory mediators. Resolvin-D1 (RvD1) elicits potent anti-inflammatory and pro-resolving effects in various pathological models. In this study, we aimed to examine whether RvD1 ameliorates cardiac remodeling and hypertension triggered by angiotensin II. Methods and resultsAlzet® osmotic mini-pumps filled with angiotensin II (1.5 mg/kg/day) were implanted in male C57BL/6 J mice for 7 or 14 days. RvD1 (3 μg/kg/day, i.p) was administered one day after the surgery and during the complete infusion period. Blood pressure and myocardial functional parameters were assessed by echocardiography. At the end of the experimental procedure, blood and heart tissue were harvested, and plasma and histological parameters were studied. After 7 and 14 days, RvD1 reduced the increase of neutrophil and macrophage infiltration triggered by angiotensin II, and also reduced ICAM-1 and VCAM-1 expression levels. RvD1 also reduced cytokine plasma levels (IL-1β, TNF-α, IL-6, KC, MCP-1), cardiac hypertrophy, interstitial and perivascular fibrosis, and hypertension. ConclusionsThis study unveils novel cardioprotective effects of RvD1 in angiotensin II-induced hypertension and cardiac remodeling by attenuating inflammation and provides insights into a potential clinical application.

On Left Ventricle Stroke Work Efficiency in Children with Moderate Aortic Valve Regurgitation or Moderate Aortic Valve Stenosis.

The optimal timing for management of pediatric patients with moderate aortic valve disease [moderate aortic stenosis (modAS) or moderate aortic regurgitation (modAR)] remains unknown and largely unexplored. Although usually asymptomatic, the risk of increased left ventricular (LV) wall stress, irreversible myocardial fibrosis and sudden death in untreated moderate conditions warrants clearer risk stratification for appropriate timely intervention. In this study, we explore the use of a patient-specific mathematical model to introduce a new evaluative parameter of LV performance in patients with moderate aortic valve disease. Synthetic patient data (N = 520) representing healthy patients, and patients with modAS or modAR were first generated. Then, data from twenty-five pediatric patients were included in this study (healthy = 9; moderate AS = 8; modAR = 8). The effect of modAS or modAR on LV performance was evaluated by LV stroke work (LVSW) efficiency, a new non-invasive parameter. The results demonstrate that healthy patients possess a very high LVSW efficiency (synthetic data: 91 ± 2%, in vivo data: 92 ± 3%). However, modAS patients have a significant reduction in LVSW efficiency (synthetic data: 78 ± 2%, in vivo data: 76 ± 5%, p < 0.05), whereas modAR patients had the lowest LVSW efficiency (synthetic data: 58 ± 3%, in vivo data: 66 ± 7%; p < 0.05). This highlights that patients with moderate aortic valve disease require careful myocardial assessment, regardless of onset of clinical symptoms as their LV performance is significantly reduced. The evaluation of LVSW efficiency offers a promising avenue for future stratification of mixed aortic valve disease for optimal timing of management and intervention.