Fibrofatty Tissue Research Articles

Vaccine-Associated Anaphylactic Shock in a Springer Spaniel Dog with Arrhythmogenic Right Ventricular Cardiomyopathy

A 5-year-old female Springer Spaniel dog was submitted for necropsy after sudden death following vaccination against Leptospira spp. Gross examination revealed a diffuse dark red discolouration of skeletal musculature, severe diffuse congestion of all the abdominal organs and a contracted spleen. Severe dilation and reduction in wall width was seen in the right ventricle and histological examination revealed multifocal replacement of the right ventricular myocardium by a large amount of fibrofatty tissue. Pathological changes were consistent with post-vaccinal anaphylactic shock in a dog with arrhythmogenic right ventricular cardiomyopathy (ARVC), a rare condition typical of Boxer dogs but not previously reported in Springer Spaniels. Canine vaccine-associated adverse events are discussed and ARVC is compared with the corresponding human cardiac condition.

Celecoxib induces adipogenic differentiation of hemangioma-derived mesenchymal stem cells through the PPAR-γ pathway in vitro and in vivo.

Infantile hemangioma (IH) is a benign tumor that produces a permanent scar or a mass of fibro-fatty tissue after involution in 40-80% of cases. Celecoxib is an inhibitor of cyclooxygenase-2 (COX-2), and can inhibit angiogenesis and fibrosis. The present study aimed to clarify whether celecoxib is able to induce tumor regression with minimal side effects. For that purpose, the regulation of celecoxib in the involution of IH was investigated in an IH model. Hemangioma-derived mesenchymal stem cells (Hem-MSCs) were isolated from proliferating specimens, and an IH model was established by injecting these cells into nude mice. Celecoxib was administered in vitro and in vivo. Oil Red O staining and reverse transcription-quantitative-PCR were used to detect the adipogenic differentiation of Hem-MSCs. Histologic analysis and immunohistochemical staining of the tumor xenografts were performed to investigate the pathological evolution of the tumor. The results showed that celecoxib inhibited the proliferation and induced the adipogenic differentiation of Hem-MSCs in vitro. In vivo, adipocytes were only present in the celecoxib group at week 4, while a larger number of fibroblasts and collagenous fibers could be observed in the basic fibroblast growth factor group. Therefore, celecoxib may be a potential agent used for IH treatment by inducing adipogenesis and inhibiting fibroblast formation.

A Tachycardia in Disguise.

A Tachycardia in Disguise.

Atomic Force Microscopy (AFM) Applications in Arrhythmogenic Cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disorder characterized by progressive replacement of cardiomyocytes by fibrofatty tissue, ventricular dilatation, cardiac dysfunction, arrhythmias, and sudden cardiac death. Interest in molecular biomechanics for these disorders is constantly growing. Atomic force microscopy (AFM) is a well-established technic to study the mechanobiology of biological samples under physiological and pathological conditions at the cellular scale. However, a review which described all the different data that can be obtained using the AFM (cell elasticity, adhesion behavior, viscoelasticity, beating force, and frequency) is still missing. In this review, we will discuss several techniques that highlight the potential of AFM to be used as a tool for assessing the biomechanics involved in ACM. Indeed, analysis of genetically mutated cells with AFM reveal abnormalities of the cytoskeleton, cell membrane structures, and defects of contractility. The higher the Young’s modulus, the stiffer the cell, and it is well known that abnormal tissue stiffness is symptomatic of a range of diseases. The cell beating force and frequency provide information during the depolarization and repolarization phases, complementary to cell electrophysiology (calcium imaging, MEA, patch clamp). In addition, original data is also presented to emphasize the unique potential of AFM as a tool to assess fibrosis in cardiac tissue.

Autonomic nerves in myocardial sleeves around caval veins: Potential role in cardiovascular mortality?

BackgroundQuantitative changes in the cardiac autonomic nervous system may play an important role in the pathogenesis of various cardiovascular diseases. In the present morphological analysis, we aimed to study autonomic nerve density in myocardial sleeves and surrounding fibro-fatty tissue around caval veins. We correlated the nerve distribution with cardiovascular mortality and a history of atrial fibrillation. Materials and MethodsA total of 24 autopsied adult hearts were excised together with the superior and inferior vena cava and grouped according to the immediate and underlying causes of death (cardiovascular vs. non-cardiovascular), and documented heart rhythm history (atrial fibrillation vs. sinus rhythm). The density of autonomic nerves was quantified by measuring the area of immunohistochemical staining for sympathetic (tyrosine hydroxylase, TH) and parasympathetic (choline acetyltransferase, CHAT) nerves and ganglia. Growth-associated protein 43 (GAP43) was used as a neural growth marker. ResultsThe mean density of TH-positive nerves in the superior vena cava myocardial sleeves was significantly decreased between groups with documented underlying cardiovascular vs. non-cardiovascular cause of death (mean density ± standard deviation (SD): 704.81±1016.41 µm2/mm2 vs. 2391.01±1841.37 µm2/mm2; P = .008). Similarly, the nerve density of GAP43-positive nerves in the superior vena cava myocardial sleeves was significantly lower in subjects with documented underlying cardiovascular cause of death (mean density ± SD: 884.74±1240.16 µm2/mm2 vs. 2132.89±1845.89 µm2/mm2; P = .040). The mean age was significantly higher in subjects with documented underlying cardiovascular vs. non-cardiovascular cause of death (mean age ± SD: 69.2±11.9 years, vs. 57.5±11.2 years, P = .016). No differences were found in nerve densities of TH-positive (953.01±1042.93 µm2/mm2 vs. 919.26±1677.58 µm2/mm2), CHAT-positive (180.8±532.9 µm2/mm2 vs. 374.22±894.76 µm2/mm2), and GAP43-positive nerves (593.58±507.97 µm2/mm2 vs. 1337.34±1747.69 µm2/mm2) in myocardial sleeves around the inferior vena cava between groups with documented immediate cardiovascular vs. non-cardiovascular cause of death. Similarly, no differences were found between groups with documented underlying cardiovascular vs. non-cardiovascular cause of death (TH: 717.23±887.31 µm2/mm2 vs. 1365.51±2149.10 µm2/mm2; CHAT: 256.18±666.86 µm2/mm2 vs. 368.53±959.47 µm2/mm2; GAP43: 661.21±839.51 µm2/mm2 vs. 1759.90±2008.80 µm2/mm2). Moreover, there was no association found in nerve densities between subjects with documented atrial fibrillation vs. sinus rhythm (TH: 235.07±425.69 µm2/mm2 vs. 1166.08±1563.84 µm2/mm2; CHAT: 648.59±1017.33 µm2/mm2 vs. 175.31±641.65 µm2/mm2; GAP43: 990.17±1315.18 µm2/mm2 vs. 1039.86±1467.23 µm2/mm2). ConclusionsDecrease of superior vena cava myocardial sleeve sympathetic nerves may be associated with cardiovascular mortality and/or aging. No difference in autonomic innervation was found between subjects with documented atrial fibrillation vs. sinus rhythm.

Successful Treatment of Symptomatic Fibrofatty Tissue of an Involuted Infantile Hemangioma on the Cheek With Intralesional Deoxycholic Acid and Pulsed Dye Laser.

Successful Treatment of Symptomatic Fibrofatty Tissue of an Involuted Infantile Hemangioma on the Cheek With Intralesional Deoxycholic Acid and Pulsed Dye Laser.

PIK3CA mutation correlates with mTOR pathway expression but not clinical and pathological features in Fibro-adipose vascular anomaly (FAVA)

BackgroundFibro-adipose vascular anomaly (FAVA) is a rare and new entity of vascular anomaly. Activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene were identified at a frequency of 62.5% in FAVA cases. The PIK3CA mutations excessively activate mammalian target of rapamycin (mTOR) pathway, which promotes angiogenesis and lymphangiogenesis, implying that PIK3CA mutations may act as drivers of FAVAs. This study investigated the correlations between PIK3CA mutational status, clinicopathological features and immunohistochemical expression of the mTOR pathway in a series of FAVA.MethodsWe retrospectively evaluated the clinical and pathological findings of four FAVA cases. We performed next-generation sequencing (NGS) with a custom panel of genes associated with the mTOR pathway and genes responsible for other vascular anomalies; followed by direct sequencing and immunohistochemical analysis of the mTOR pathway.ResultsTwo PIK3CA-mutation cases and two PIK3CA-wild-type (wt) cases exhibited similar typical clinical features of FAVA. Histological analysis revealed venous malformation, lymphatic malformation, nerves containing enlarged abnormal vessels and fibrofatty tissue were observed regardless of PIK3CA mutational status. In contrast to clinical and histological findings, the immunohistochemical expression of activated AKT and mTOR that are upstream of the mTOR pathway was detected in abnormal vessels of PIK3CA-mutation cases but not in those of PIK3CA-wt cases. However, activated eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) and ribosomal protein S6 kinase 1 (S6K1), both of which are downstream effectors of the mTOR pathway, were expressed in abnormal vessels of both PIK3CA-mutation and PIK3CA-wt cases. Furthermore, targeting NGS did not find any common genetic mutations involved in the mTOR pathway among PIK3CA-wt cases.ConclusionsThere was no significant association between the presence of PIK3CA mutations and the clinicopathological features of FAVA, suggesting that the PIK3CA gene is not necessarily involved in the onset of FAVA. FAVAs lacking PIK3CA mutations may be caused by other gene mutations that activate 4EBP1 and S6K1.

Multimodality Approach to Lymphedema Surgery Achieves and Maintains Normal Limb Volumes: A Treatment Algorithm to Optimize Outcomes.

Surgical treatment of advanced lymphedema is challenging and outcomes are suboptimal. Physiologic procedures including lymphaticovenous anastomosis (LVA) and vascularized lymph node transfer (VLNT) improve lymphatic flow but cannot reverse fibrofatty tissue deposition, whereas liposuction removes fibrofatty tissue but cannot prevent disease progression. The adjunctive use of nanofibrillar collagen scaffolds (BioBridgeTM) can promote lymphangiogenesis. We report a treatment algorithm utilizing a multimodality approach to achieve sustained normal limb volumes in patients with stage II-III lymphedema. A retrospective review of late stage II-III lymphedema patients treated with liposuction, physiologic procedures, and BioBridgeTM from 2016 through 2019 was conducted. Treatment outcome in the form of excess volume reduction is reported. Total of 14 patients underwent surgical treatment of late stage II and III lymphedema according to our triple therapy algorithm. Patients had a baseline median volume excess of 29% (19.8, 43.3%). The median volume excess was improved to 0.5% (−4.3, 3.8%) at 14.4 months from the first stage surgery (p < 0.05) and further improved to −1.0% (−3.3, 1.3%) after triple therapy with BB placement at 24.6 months. A triple therapy surgical treatment algorithm can optimize outcomes and achieve sustained normalization of limb volume in late stage II-III lymphedema. The incorporation of nanofibrillar collagen scaffold technology allows for improved and sustained volume reduction.

Miniseries 2-Septal and paraseptal accessory pathways-Part I: The anatomic basis for the understanding of para-Hisian accessory atrioventricular pathways.

Although the anatomy of the atrioventricular conduction axis was well described over a century ago, the precise arrangement in the regions surrounding its transition from the atrioventricular node to the so-called bundle of His remain uncertain. We aimed to clarify these relationships. We have used our various datasets to examine the development and anatomical arrangement of the atrioventricular conduction axis, paying particular attention to the regions surrounding the point of penetration of the bundle of His. It is the areas directly adjacent to the transition of the atrioventricular conduction axis from the atrioventricular node to the non-branching atrioventricular bundle that constitute the para-Hisian areas. The atrioventricular conduction axis itself traverses the membranous part of the ventricular septum as it extends from the node to become the bundle, but the para-Hisian areas themselves are paraseptal. This is because they incorporate the fibrofatty tissues of the inferior pyramidal space and the superior atrioventricular groove. In this initial overarching review, we summarize the developmental and anatomical features of these areas along with the location and landmarks of the atrioventricular conduction axis. We emphasize the relationships between the inferior pyramidal space and the infero-septal recess of the subaortic outflow tract. The details are then explored in greater detail in the additional reviews provided within our miniseries. Our anatomical findings, described here, provide the basis for our concomitant clinical review of the so-called para-Hisian arrhythmias. The findings also provide the basis for understanding the other variants of ventricular pre-excitation.

OP4: Posterior Auricular Perichondrial Cutaneous Graft for Stable Reconstruction of Nasal Defects: Long-Term Outcomes

INTRODUCTION: The posterior auricular perichondrial cutaneous graft (PCCG) was described in 2005 by Kalbermatten et al. as a functional, stable and aesthetic reconstructive option in case of cartilage or fibrofatty tissue defects of the nasal tip or ala. The composite graft is harvested using a posterior auricular donor site which is closed with a postauricular transposition flap, thus avoiding resection from the anterior conchal bowl. The present study aims at reporting long-term outcomes of the procedure. MATERIALS AND METHODS: We conducted a retrospective review of all patients undergoing nasal tip reconstruction with PCCG between 2005 and 2020. Graft survival, donor-site morbidity, nostril stability, reoperation rate and aesthetic outcomes were assessed at long follow-up. RESULTS: We identified 13 patients undergoing PCCG nasal reconstruction to cover defects presenting an average size of 2 cm2 on the ala and 2.5 cm2 on the tip after basal cell carcinoma resection. Twelve patients showed primary complete healing, while reoperation was required in one case due to partial necrosis of the graft. At a mean follow-up of 14.5 months, nostril stability and symmetry were achieved in all patients, while all donor sites healed uneventfully. Aesthetic outcomes were judged as satisfactory by both patients and surgeons. Oncological control was ensured by this reconstruction, allowing detection of relapse in three cases. CONCLUSION: This follow-up study confirmed the findings initially presented with a shorter 6months follow-up. The PCCG demonstrated to be a reliable and effective reconstructive option, able to restore function and aesthetic with minimal morbidity rate. Notably, the procedure allows optimal oncological control.

A rare case of macrodystrophia lipomatosa progressiva

A non-heritable congenital expansion of a digit is known as macrodactyly. It happens as a result of a mutation in the PIK3CA pathway, which regulates healthy cell proliferation. It is usually associated with gigantism, neurofibromatosis, lipofibromatosis, digital hyperostosis and hemihypertrophy. It is not always evident at birth, but at about age 2, the affected fingers begin to grow significantly faster than the normal fingers. Ninety percent (90%) of it is unilateral, and 70% of it involves more than one digit-most often the index. The expansion might only affect the digit or it might spread to the palm, forearm, or arm. The digit may exhibit angulation deformity. The distal interphalangeal joint occasionally exhibits motion restriction. The patient presented to us with a loss of two-point discrimination and sensory deficit. In this condition, the motor deficit is rarely seen. Our patient reported a tingling sensation and the possibility of carpal tunnel syndrome was ruled out as an enlarged median nerve might result in carpal tunnel syndrome. Inspection & palpation revealed thick, fibrofatty tissue with restricted movements. The patient’s symptoms were relieved by NSAIDs and Pregabalin 75mg, symptomatic relief was present, and the patient was advised debulking surgery as the treatment modality.

Arrhythmogenic Right Ventricular Dysplasia Diagnosed in a Patient with Long-term Undiagnosed Syncope

Arrhythmogenic Right Ventricular Dysplasia (ARVD) is an inherited cardiomyopathy which represents progressive replacement of right ventricular myocardium with fibrofatty tissue. In the present case, a 42-year-old male presented to the hospital as he fell down, due to syncope. He had a history of recurrent syncopal in past 4-5 years. His chest radiogram revealed cardiomegaly (CT ratio 0.64), repeat electrocardiogram showed symmetric T-wave inversions and epsilon waves in right precordial V1, V2 and V3 leads, and echocardiogram revealed mild left ventricular dysfunction (ejection fraction - 45%) and dilated right atrium and ventricle. Cardiac Magnetic Resonance Imaging (MRI) confirmed the diagnosis of ARVD.The patient was advised for the placement of an Automatic Implantable Cardioverter Defibrillator (AICD), but he denied for this treatment. Thus, he was managed with anti-arrhythmic drugs and was advised for regular follow-up. The patient was followed-up for six months where episodes of syncope had significantly reduced to one in six months but need of AICD implantation was still there to avoid sudden cardiac death.

A traumatic injury leading the lipoma of neck: a rare image.

A 58 years old male visited our hospital with the complaint of swelling over the posterior aspect of the neck after sustaining a trauma as a result of a fall of a cement slab over him 5 years back. The patient is under a combination of metoprolol and telmisartan medication for the rectification of hypertension for 10 years. The patient got admitted to the hospital for the above complaint and has undergone a histopathology report, MRI, and USG investigation. In the histopathology report, we received a single container labelled as a resected specimen of large lipoma. On the cut section, a solid, yellowish, homogenous area was identified. MRI investigation reported a lesion over the nape of the neck size measuring from 25x20x8cm in size. USG report stated a lesion over the nape of the neck and occipital region with the dimensions of the left side as 53x25mm approximately, right side as 58x31.5Â mm approximately. After both MRI and USG investigation, the patient was diagnosed with lipoma over the nape of the neck and occipital region. The patient had gone through two separate operations in a spare of 11 days. Complete excision of Excessive fibrofatty tissue size 10x15 cm lipoma was done. Flap was approximated and romovac drian no 14 placed. Closure was done with ethilon2-0 ac. PPd debridement was done with secondary suturing. Hemostasis was confirmed and Patient stable. Shifted to ward and got discharged after 1 week with prescribed medications and physiotherapy exercise.

Restoration of neglected fracture dislocation hip in elderly: a case report

&lt;p class="abstract"&gt;Neglected traumatic fracture dislocation of the hip is a challenging problem due to soft tissue contractures, adhesions, fibro fatty tissue filling acetabulum, avascular necrosis, arthritis and myositis ossificans. These types of injury often get missed at initial evaluation in the presence of distracting injuries and in poly trauma patients. Femoral head fractures account for only 7-16% of all hip fracture dislocations, with combined femoral head and acetabular fractures in elderly being even lower. Literature favours primary hip replacement as compared to hip salvage in age above 60 years and in patients with neglected hip fracture dislocations of more than 3 months duration due to high chances of afore mentioned complications. Here, we report a case of 69 years old male with neglected hip fracture dislocation associated with posterior acetabular wall and femoral head fracture for the challenges in management with a total hip replacement.&lt;/p&gt;

Clinical, Radiological and Histopathological Features of Patients With Lacrimal Gland Enlargement.

The purpose of this study was to describe the radiologic and histopathologic features of lacrimal gland in patients presenting with lacrimal gland enlargement. We retrospectively retrieved the data of patients with lacrimal gland enlargement in Farabi Eye Hospital between 2012 and 2017. These data included demographics, the patients' facial photographs, orbital CT-scans, and histopathological findings of lacrimal gland biopsies. Forty-seven patients (15 men and 32 women) were enrolled in this study with a median age of 37.9 years (range, 15-79 years). Histopathologic diagnoses were chronic dacryoadenitis in 26 cases (55.32%), IgG4-related disease in 6 patients (12.77%), two cases of acute dacryoadenitis, two cases of non-necrotizing granulomatous inflammation, two cases of Non-Hodgkin's B-cell lymphoma, two cases of adenoid cystic carcinoma and two cases of mixed tumor (4.26% each), as well as one case of conjunctival epithelial cyst, and one case of benign lymphoid tissue and fibrofatty tissue (2.13%). In two samples (4.26%), biopsy revealed normal lacrimal glands. Interestingly, in two cases with relapsing lacrimal gland enlargement, different histopathologic diagnoses were found in biopsies taken from each lacrimal gland at different times. The average size of enlarged lacrimal glands was 19.67 mm × 7.06 mm on axial CT scan and 19.44 mm × 6.20 mm on coronal CT scan. Tissue biopsy is needed for diagnosis of lacrimal gland enlargement because it is difficult to distinguish the type of the lacrimal gland pathology based solely on clinical or radiological presentation.

Sequelae following infantile haemangiomas treated with propranolol.

Oral propranolol accelerates the involution of infantile haemangiomas (IHs). However, it is not clear whether IHs treated with oral propranolol are associated with fewer sequelae than when left untreated. To quantify and describe sequelae associated with IHs treated with oral propranolol, and to explore whether treated IHs are associated with fewer sequelae than untreated IHs. This multicentre, retrospective, cohort study included patients with IH treated with oral propranolol ≥2mg/kg for at least six months, with photographic images available at baseline and at age 4-5 years. A historical comparison cohort comprised 185 patients with untreated IHs. Main outcomes/measures were: IH features, treatment characteristics and type/degree of sequelae. Oral propranolol, most commonly at 2mg/kg/day (mean duration: nine months), was initiated in 171 patients (mean age: 6.02 months). After treatment, 125 of 171 (73.1%) IHs were associated with no/minimal sequelae. The most common sequelae were telangiectasia (78%), fibrofatty tissue (37%) and anetodermic skin (28%). Deep IHs were associated with significantly fewer sequelae than other subtypes. Ulceration appeared to increase the likelihood of severe sequelae. IHs with a stepped border was associated with more severe sequelae than those with a progressive border (44% versus 27%, p < 0.05). Treated IHs resolved without sequelae or were associated with a sequela that did not need correction in 27.7% more cases than untreated IHs (RR: 1.61; p < 0.001). Among IHs treated with oral propranolol, 73% resolved without, or were associated with minimal sequelae. Deep IHs were associated fewer sequelae than other subtypes. Oral propranolol decreased the likelihood of IH sequelae requiring correction.

Istaroxime treatment ameliorates calcium dysregulation in a zebrafish model of phospholamban R14del cardiomyopathy

The heterozygous Phospholamban p.Arg14del mutation is found in patients with dilated or arrhythmogenic cardiomyopathy. This mutation triggers cardiac contractile dysfunction and arrhythmogenesis by affecting intracellular Ca2+ dynamics. Little is known about the physiological processes preceding induced cardiomyopathy, which is characterized by sub-epicardial accumulation of fibrofatty tissue, and a specific drug treatment is currently lacking. Here, we address these issues using a knock-in Phospholamban p.Arg14del zebrafish model. Hearts from adult zebrafish with this mutation display age-related remodeling with sub-epicardial inflammation and fibrosis. Echocardiography reveals contractile variations before overt structural changes occur, which correlates at the cellular level with action potential duration alternans. These functional alterations are preceded by diminished Ca2+ transient amplitudes in embryonic hearts as well as an increase in diastolic Ca2+ level, slower Ca2+ transient decay and longer Ca2+ transients in cells of adult hearts. We find that istaroxime treatment ameliorates the in vivo Ca2+ dysregulation, rescues the cellular action potential duration alternans, while it improves cardiac relaxation. Thus, we present insight into the pathophysiology of Phospholamban p.Arg14del cardiomyopathy.

Fibro-adipogenic progenitors in skeletal muscle homeostasis, regeneration and diseases.

Skeletal muscle possesses a remarkable regenerative capacity that relies on the activity of muscle stem cells, also known as satellite cells. The presence of non-myogenic cells also plays a key role in the coordination of skeletal muscle regeneration. Particularly, fibro-adipogenic progenitors (FAPs) emerged as master regulators of muscle stem cell function and skeletal muscle regeneration. This population of muscle resident mesenchymal stromal cells has been initially characterized based on its bi-potent ability to differentiate into fibroblasts or adipocytes. New technologies such as single-cell RNAseq revealed the cellular heterogeneity of FAPs and their complex regulatory network during muscle regeneration. In acute injury, FAPs rapidly enter the cell cycle and secrete trophic factors that support the myogenic activity of muscle stem cells. Conversely, deregulation of FAP cell activity is associated with the accumulation of fibrofatty tissue in pathological conditions such as muscular dystrophies and ageing. Considering their central role in skeletal muscle pathophysiology, the regulatory mechanisms of FAPs and their cellular and molecular crosstalk with muscle stem cells are highly investigated in the field. In this review, we summarize the current knowledge on FAP cell characteristics, heterogeneity and the cellular crosstalk during skeletal muscle homeostasis and regeneration. We further describe their role in muscular disorders, as well as different therapeutic strategies targeting these cells to restore muscle regeneration.

A 73-year-old woman with delayed intra-abdominal and systemic sepsis following complicated aortobifemoral bypass

A 73-year-old woman with delayed intra-abdominal and systemic sepsis following complicated aortobifemoral bypass

Abstract 12592: Acute Administration of N-Acytylcysteine Leads to Highly Specific Sub-Regional Changes in AF Electrogram Characteristics - A New Way to ‘Uncover’ Regions of High Oxidative Injury in the Fibrillating Atrium?

Introduction: It is currently not possible to measure and therapeutically target oxidative injury (OI) in the intact fibrillating atrium. Hypothesis: We postulated that measurement of AF electrogram characteristics after acute administration of a reactive oxygen species (ROS) scavenger can help ‘uncover’ regions of high OI in the fibrillating human atrium. Methods: We mapped in both atria pre/post NAC (intravenous, 100mg/kg) in 15 persistent AF dogs (3-14 weeks rapid atrial pacing) using a high-density epicardial mapping-plaque (6 atrial regions in both atria, 130 electrodes, electrode-distance 2.5mm) and in 4 patients using the HD-grid catheter. We quantified the OS-levels as ratio of oxidatively damaged nuclei ( Figure A ) against the total number in 8-OHdG staining (N=36) and the degree of dense fibro-fatty tissue in Masson’s trichrome stained tissue (N=24) using Qupath. We analyzed cycle length (CL) and dominant frequency (DF) in ‘hot spot’-sub-region sizes with &gt;10% change pre vs. post NAC. Results: Oxidative stress (OS) levels, highest in the left atrial free wall, lowest in the appendages increased with increasing degree of fibro-fatty tissue (R=0.6,P&lt;0.05) and with decreasing cycle length (R=0.5, P&lt;0.05) in all regions ( Figure C ). NAC selectively reduced AF characteristics in ‘hot spot’-sub-regions ( Figure D ). OS level correlated with delta CL, delta DF, and delta Organization Index in delta maps (NAC - baseline) (R=0.5, P&lt;0.05, all comparisons) ( Figure E) . In patients, NAC ( Figure G) reduced AF characteristics in subregions ( Figure H) and increased cycle length from 210±50ms to 252±18ms (P&lt;0.05) in the left atrium ( Figure I ). Conclusions: OS-level correlated with the degree of dense fibro-fatty tissue and with electrogram measures in both atria. Acute scavenging of ROS reduced AF characteristics in the left atrium in dogs and patients. We might have found a new way to target regions of high OS in the atrium in the individual patient.