Septal Volume Research Articles

Chronic Hypoxia in an EXTrauterine Environment for Neonatal Development Impairs Lung Development.

Severe fetal hypoxia poses a significant risk to lung development resulting in severe postnatal complications. Existing chronic hypoxia animal models lack the ability to achieve pathologically reduced fetal oxygen without compromising animal development, placental blood flow, or maternal health. Using an established model of isolated chronic hypoxia involving the Extrauterine Environment for Neonatal Development (EXTEND), we are able to investigate the direct impact of fetal hypoxia on lung development. Oxygen delivery to preterm fetal lambs (105-110 days GA) delivered by cesarean section was reduced, and animals were supported on EXTEND through the canalicular or saccular stage of lung development. Fetal lambs in hypoxic conditions showed significant growth restriction compared to their normoxic counterparts. We also observed modest aberrant vascular remodeling in the saccular group after hypoxic conditions with decreased macrovessel numbers, microvascular endothelial cell numbers, and increased peripheral vessel muscularization. In addition, fetal hypoxia resulted in enlarged distal airspaces and decreased septal wall volume. Moreover, there was a reduction in mature SFTPB and processed SFTPC protein expression concomitant with a decrease in AT2 cell number. These findings demonstrate that maternally-independent fetal hypoxia predominantly impacts distal airway development, AT2 cell number, and surfactant production with mild effects on the vasculature.

Assessment of the Change in the Nasal Septum and Nasal Profile After Le Fort I With Cone Beam Computed Tomography.

This study aimed to determine the relationship between nasal changes and the amount of advancement, impaction, and downward movement of the maxilla after Le Fort I osteotomy. The study included 48 patients who underwent Le Fort I surgery and had pre- and postoperative cone-beam computed tomography records. Changes in the nasal septum were evaluated by measuring septal deviation angles and volumes. In addition, nasolabial angle and width of nasal and alar base were examined. Groups were determined according to the movement of point A (the deepest point on the curvature of the maxillary alveolar process), using a threshold of 1.5 mm for vertical movements and 4 mm for sagittal movements. This resulted in the comparison of 6 groups of 8 people each. Results are presented as mean and standard deviation or median and range depending on the data distribution. Significance level was accepted as P < 0.05. There were no significant differences for each group on its own septal deviation volume or angle values pre/postoperatively. Groups 3 and 5, which both had at least 1.5 mm of impaction, showed significant changes in both deviation angle and volume between the preoperative and postoperative measurements. Nasolabial angle did not show significant changes between groups. Alar base width and nasal width increase was significantly highest in Group 1, which has more than 4 mm sagittal movement and less than 1.5 mm vertical movement. Le Fort I osteotomy may lead to undesirable changes in the spatial positioning of the nasal septum. The results of this study suggest that maxillary advancement does not significantly impact septal deviation, whereas maxillary impaction increases the amount of deviation. In addition, nasal width and alar base width tended to increase, and the nasolabial angle tended to decrease slightly, regardless of the direction of movement of the maxilla after orthognathic surgery. Surgeons should consider increased nasal septal deviation risks when planning impaction of the maxilla. The soft tissue changes in the nose vary according to different directions and amounts of Le Fort I surgery.

Mesenchymal stromal cell extracellular vesicles improve lung development in mechanically ventilated preterm lambs.

Novel therapies are needed for bronchopulmonary dysplasia (BPD) because no effective treatment exists. Mesenchymal stromal cell extracellular vesicles (MSC-sEVs) have therapeutic efficacy in a mouse pup neonatal hyperoxia BPD model. We tested the hypothesis that MSC-sEVs will improve lung functional and structural development in mechanically ventilated preterm lambs. Preterm lambs (∼129 days; equivalent to human lung development at ∼28 wk gestation) were exposed to antenatal steroids, surfactant, caffeine, and supported by mechanical ventilation for 6-7 days. Lambs were randomized to blinded treatment with either MSC-sEVs (human bone marrow MSC-derived; 2 × 1011 particles iv; n = 8; 4 F/4 M) or vehicle control (saline iv; 4 F/4 M) at 6 and 78 h post delivery. Physiological targets were pulse oximetry O2 saturation 90-94% ([Formula: see text] 60-90 mmHg), [Formula: see text] 45-60 mmHg (pH 7.25-7.35), and tidal volume 5-7 mL/kg. MSC-sEVs-treated preterm lambs tolerated enteral feedings compared with vehicle control preterm lambs. Differences in weight patterns were statistically significant. Respiratory severity score, oxygenation index, A-a gradient, distal airspace wall thickness, and smooth muscle thickness around terminal bronchioles and pulmonary arterioles were significantly lower for the MSC-sEVs group. S/F ratio, radial alveolar count, secondary septal volume density, alveolar capillary surface density, and protein abundance of VEGF-R2 were significantly higher for the MSC-sEVs group. MSC-sEVs improved respiratory system physiology and alveolar formation in mechanically ventilated preterm lambs. MSC-sEVs may be an effective and safe therapy for appropriate functional and structural development of the lung in preterm infants who require mechanical ventilation and are at risk of developing BPD.NEW & NOTEWORTHY This study focused on potential treatment of preterm infants at risk of developing bronchopulmonary dysplasia (BPD), for which no effective treatment exists. We tested treatment of mechanically ventilated preterm lambs with human mesenchymal stromal cell extracellular vesicles (MSC-sEVs). The results show improved respiratory gas exchange and parenchymal growth of capillaries and epithelium that are necessary for alveolar formation. Our study provides new mechanistic insight into potential efficacy of MSC-sEVs for preterm infants at risk of developing BPD.

The expression of the surfactant proteins SP-A and SP-B during postnatal alveolarization of the rat lung.

Surfactant-specific proteins (SP) are responsible for the functional and structural integrity as well as for the stabilization of the intra-alveolar surfactant. Morphological lung maturation starts in rat lungs after birth. The aim of this study was to investigate whether the expression of the hydrophilic SP-A and the hydrophobic SP-B is associated with characteristic postnatal changes characterizing morphological lung maturation. Stereological methods were performed on the light microscope. Using immunohistochemical and molecular biological methods (Western Blot, RT-qPCR), the SP-A and SP-B of adult rat lungs and of those with different postnatal developmental stages (3, 7, 14 and 21 days after birth) were characterized. As signs of alveolarization the total septal surface and volume increased and the septal thickness decreased. The significantly highest relative surface fraction of SP-A labeled alveolar epithelial cells type II (AEII) was found together with the highest relative SP-A gene expression before the alveolarization (3th postnatal day). With the downregulation of SP-A gene expression during and after alveolarization (between postnatal days 7 and 14), the surface fraction of the SP-A labeled AEII also decreased, so they are lowest in adult animals. The surface fraction of SP-B labeled AEII and the SP-B gene expression showed the significantly highest levels in adults, the protein expression increased also significantly at the end of morphological lung maturation. There were no alterations in the SP-B expression before and during alveolarization until postnatal day 14. The protein expression as well as the gene expression of SP-A and SP-B correlated very well with the total surface of alveolar septa independent of the postnatal age. The expression of SP-A and SP-B is differentially associated with morphological lung maturation and correlates with increased septation of alveoli as indirect clue for alveolarization.

Opposing effects of thyroid hormones on hypothalamic subunits and limbic structures in hyperthyroidism patients: A comprehensive volumetric study.

Thyroid hormones play a critical role in brain development, but paradoxically, patients with hyperthyroidism often exhibit cognitive decline and irritability. This study aims to explore the pattern of atrophy in hyperthyroid patients, changes in specific areas of the brain, including hypothalamic subfields and limbic structures, and their relationships with hormonal levels and psychometric tests. This prospective cross-sectional study involves 19 newly diagnosed, untreated hyperthyroid patients, and 15 age and gender-matched control subjects. The participants underwent psychometric and cognitive tests and volumetric MRI. The hypothalamic subfield (anterior-inferior, anterior-superior, superior-tubular, inferior-tubular, and posterior hypothalamus) and limbic structures (fornix, basal forebrain, nucleus accumbens, and septal nucleus) were segmented using voxel-based morphometry, surface-based morphometry, and deep learning algorithms. The groups were compared using the t-test, and correlation analyses were performed between clinical parameters and volumetric measurements. The correlation between hormonal parameters and volumetric measurements in patient and control groups was assessed with the Meng test. Hyperthyroid patients displayed widespread grey matter loss and sulcal shallowing in the left hemisphere. However, no local gyrification index changes or cortical thickness variations were detected. The limbic structures and hypothalamic subunits did not show any volume discrepancies. Free thyroxine in the patient group negatively correlated with bilateral anterior-inferior and right septal nucleus, but positively correlated with left anterior-inferior in the control group. Thyroid stimulating hormone in the patient group showed a positive correlation with bilateral fornix volume, a correlation absent in the control group. Disease duration negatively correlated with right anterior-inferior, right tubular inferior, and right septal nucleus. Changes in cognitive and psychometric test scores in the patient group correlated with the bilateral septal nucleus volume. Hyperthyroidism primarily leads to a reduction in grey matter volume and sulcal shallowing. Thyroid hormones have differing volumetric effects in limbic structures and hypothalamic subunits under physiological and hyperthyroid conditions.

Volume-outcome relationship in septal myectomy for hypertrophic obstructive cardiomyopathy

BackgroundSeptal myectomy is the gold standard treatment for refractory hypertrophic obstructive cardiomyopathy. The present study characterized the association of septal myectomy volume and cardiac surgery volume with outcomes after septal myectomy. MethodsAdults undergoing septal myectomy for hypertrophic obstructive cardiomyopathy were identified in the 2016 to 2019 Nationwide Readmissions Database. Centers were grouped into low-, medium-, and high-volume hospitals by tertiles based on institutional septal myectomy caseload. Overall cardiac surgery volume was similarly assessed. Generalized linear models were used to test the association between hospital septal myectomy or cardiac surgery volume and in-hospital mortality, mitral valve repair, and 90-day non-elective readmission. ResultsOf 3,337 patients, 30.8% underwent septal myectomy at high-volume hospitals, whereas 39.1% were managed at low-volume hospitals. Patients at high-volume hospitals had a similar burden of comorbidities at low-volume hospitals, although congestive heart failure was more prevalent at high-volume hospitals. Despite comparable rates of mitral regurgitation, patients more commonly avoided mitral valve intervention at high-volume hospitals compared with low-volume hospitals (72.9% vs 68.3%; P = .007). After risk adjustment, high-volume hospital status was associated with reduced odds of mortality (0.24; 95% CI, 0.08–0.77) and readmission (0.59; 95% CI, 0.3–0.97). Among cases requiring mitral intervention, high-volume hospital status was associated with greater odds of valve repair (5.33; 95% CI, 2.54–11.13) relative to low-volume hospitals. Overall cardiac surgery volume was not associated with any studied outcome. ConclusionGreater septal myectomy volume, but not overall cardiac surgery volume, was associated with reduced mortality and greater mitral valve repair relative to replacement after septal myectomy. These findings suggest that septal myectomy for hypertrophic obstructive cardiomyopathy should be performed at centers with expertise in this operation.

Activation of medial septum cholinergic neurons restores cognitive function in temporal lobe epilepsy.

Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal sclerosis. There is no effective treatment for cognitive impairment. Medial septum cholinergic neurons have been reported to be a potential target for controlling epileptic seizures in temporal lobe epilepsy. However, their role in the cognitive impairment of temporal lobe epilepsy remains unclear. In this study, we found that patients with temporal lobe epilepsy with hippocampal sclerosis had a low memory quotient and severe impairment in verbal memory, but had no impairment in nonverbal memory. The cognitive impairment was slightly correlated with reduced medial septum volume and medial septum-hippocampus tracts measured by diffusion tensor imaging. In a mouse model of chronic temporal lobe epilepsy induced by kainic acid, the number of medial septum cholinergic neurons was reduced and acetylcholine release was reduced in the hippocampus. Furthermore, selective apoptosis of medial septum cholinergic neurons mimicked the cognitive deficits in epileptic mice, and activation of medial septum cholinergic neurons enhanced hippocampal acetylcholine release and restored cognitive function in both kainic acid- and kindling-induced epilepsy models. These results suggest that activation of medial septum cholinergic neurons reduces cognitive deficits in temporal lobe epilepsy by increasing acetylcholine release via projections to the hippocampus.

Cigarette smoke-induced airspace disease in mice develops independently of HIF-1α signaling in leukocytes.

The pathogenesis of chronic obstructive pulmonary disease (COPD), a prevalent disease primarily caused by cigarette smoke exposure, is incompletely elucidated. Studies in humans and mice have suggested that hypoxia-inducible factor-1α (HIF-1α) may play a role. Reduced lung levels of HIF-1α are associated with decreased vascular density, whereas increased leukocyte HIF-1α may be responsible for increased inflammation. To elucidate the specific role of leukocyte HIF-1α in COPD, we exposed transgenic mice with conditional deletion or overexpression of HIF-1α in leukocytes to cigarette smoke for 7 mo. Outcomes included pulmonary physiology, aerated lung volumes via microcomputed tomography, lung morphometry and histology, and cardiopulmonary hemodynamics. On aggregate, cigarette smoke increased the aerated lung volume, quasi-static lung compliance, inspiratory capacity of all strains while reducing the total alveolar septal volume. Independent of smoke exposure, mice with leukocyte-specific HIF-1α overexpression had increased quasi-static compliance, inspiratory capacity, and alveolar septal volume compared with mice with leukocyte-specific HIF-1α deletion. However, the overall development of cigarette smoke-induced lung disease did not vary relative to control mice for either of the conditional strains. This suggests that the development of murine cigarette smoke-induced airspace disease occurs independently of leukocyte HIF-1α signaling.

Left ventricular remodeling following septal myectomy in hypertrophic obstructive cardiomyopathy

ObjectivesThe purpose of this study is to determine whether or not left ventricular remodeling can be induced after septal myectomy in patients with obstructive hypertrophic cardiomyopathy, and if so, how it occurs, using gated cardiac computed tomography. MethodsFifty patients with hypertrophic obstructive cardiomyopathy who underwent septal myectomy along the septal band between March 2016 and July 2020 were retrospectively reviewed. Recent consecutive 19 patients underwent postoperative cardiac computed tomography. In these patients, volumes of the septal band and thickness of 17 left ventricular myocardial segments were measured to determine the changes after surgery. ResultsThe resection volume predicted by preoperative computed tomography and the actual resection volume were 6.7 ± 3.3 mL and 6.4 ± 2.7 mL. In-hospital mortality was 0%. Moderate or greater mitral valve regurgitation and systolic anterior motion decreased from 56% to 6% and 86% to 6%, respectively. Median preoperative ventricular septal thickness and left ventricular outflow tract pressure gradient at rest decreased from 20.0 mm (interquartile range, 17.0-24.0 mm) and 74.0 mm Hg (interquartile range, 42.5-92.5 mm Hg) to 14.0 mm (interquartile range, 11.5-16.0 mm) and 15.5 mm Hg (interquartile range, 12.1-21.5 mm Hg), respectively. Postoperative computed tomography confirmed a reduction in septal band volume of 5.7 ± 2.8 mL. Total left ventricular myocardial volume was reduced by 12.9 ± 8.8 mL, which exceeded the volume reduction of the resected septal band. All segments except the basal inferior and basal inferolateral regions showed a significant decrease in wall thickness by a median of 6.4%. ConclusionsProperly performed septal myectomy may induce remodeling of the entire left ventricle, not just the resected area.

Fetal Interventricular Septum Volume Evaluated by Three-Dimensional Ultrasound Using Spatiotemporal Image Correlation and Virtual Organ Computer-Aided Analysis in Fetuses From Pre-Gestational Diabetes Mellitus Pregnant Women.

BACKGROUNDTo assess the interventricular septum (IVS) volume of fetuses from pre-gestational diabetes mellitus (DM) pregnant women by 3-dimensional ultrasound using spatiotemporal image correlation (STIC) and virtual organ computer-aided analysis (VOCAL) methods.METHODSThis was a prospective cross-sectional study of 45 fetuses from pre-gestational DM and 45 fetuses from healthy pregnant women (controls). Only singleton pregnancies between 20 and 34 + 6 weeks of gestation were included. The fetal IVS volumes were obtained off-line using STIC and VOCAL methods. To analyze differences among variables, the Student’s t-test and Mann-Whitney U test were used. The correlation among continuous variables was determine using Spearman’s correlation test (r).RESULTSThe median of fetal IVS volume was significantly higher in pre-gestational DM than in healthy pregnant women (0.3 cm3 vs. 0.2 cm3, p = 0.032). A strong positive correlation was observed between fetal IVS volume and gestational age at the time of ultrasound examination (r = 0.75, R2 = 0.48, p < 0.0001) and between fetal IVS volume and estimated fetal weight (r = 0.63, R2 = 0.37, p < 0.0001). No significant correlation was noted between fetal IVS volume and glycated hemoglobin levels (r = −0.16, R2 = 0.01, p = 0.540) in the pre-gestational DM pregnant women.CONCLUSIONSSignificant differences were observed in fetal IVS volumes between pre-gestational and healthy mothers, with higher values in the fetuses of pre-gestational DM pregnant women.

Morphofunctional characteristics of the heart of adolescent girls who have dynamic physical activity

Summary. The article presents the study of the morphofunctional indicators of the heart in adolescent girls who go in for dynamic sports, and their comparison with the indicators of physically inactive peers. Purpose – to determine the features of physical development and morphofunctional indicators of the cardiovascular system in girls 15-17 years old who are engaged in dynamic sports. Materials and methods. 16 girls aged 15-17 years were examined, who had been involved in dynamic sports for a least two years: half of them engaged in basketball and sports dancing, as well as athletics, badminton, football, tennis, swimming, kickboxing. The comparison group consisted of 18 phisically inactive female peers. The examination included an assessment of the state of health, physical activity, anthropometry. The morphofunctional characteristics of the heart were determined using echocardiography (ECHO-CG + Doppler ECHO-CG). Results. The average indicators of the physical development of female athletes did not differ from those of physically inactive girls. 32% of girls in the first group had high growth. Systolic blood pressure in girls of the first group was higher than SBP in hypodynamic girls (p ˂ 0.05), but was within the normal values. Female athletes had significantly larger interventricular septal thickness, systolic size and volume of the left ventricle, myocardial mass and left ventricular ejection fraction than physically inactive girls (p ˂ 0.05). Conclusions. 1. Dynamic sports affect the physical development of adolecsent girls, 32% of them are tall. 2. In girls aged 15-17 who have been involved in dynamic sports for at least two years, there are changes in the morphological and functional characteristics of the heart. This is accompanied by increased systolic function of the left ventricle. These changes are adaptive, which have arisen as a result of regular physical activity. But it is possible that they may also be the initial signs of heart remodeling. 3. Medical supervision of girls with sports loads should include an assessment of the morpho-functional parameters of the heart using an annual instrumental examination. Preserving the health of a sports girls, along with ensuring the development of her physical data and achieving sports success, is the most important task for the joint work of a doctor and a sports coach.

Lung development and immune status under chronic LPS exposure in rat pups with and without CD26/DPP4 deficiency

Dipeptidyl-peptidase IV (CD26), a multifactorial integral type II protein, is expressed in the lungs during development and is involved in inflammation processes. We tested whether daily LPS administration influences the CD26-dependent retardation in morphological lung development and induces alterations in the immune status. Newborn Fischer rats with and without CD26 deficiency were nebulized with 1 µg LPS/2 ml NaCl for 10 min from days postpartum (dpp) 3 to 9. We used stereological methods and fluorescence activated cell sorting (FACS) to determine morphological lung maturation and alterations in the pulmonary leukocyte content on dpp 7, 10, and 14. Daily LPS application did not change the lung volume but resulted in a significant retardation of alveolarization in both substrains proved by significantly lower values of septal surface and volume as well as higher mean free distances in airspaces. Looking at the immune status after LPS exposure compared to controls, a significantly higher percentage of B lymphocytes and decrease of CD4+CD25+ T cells were found in both subtypes, on dpp7 a significantly higher percentage of CD4 T+ cells in CD26+ pups, and a significantly higher percentage of monocytes in CD26− pups. The percentage of T cells was significantly higher in the CD26-deficient group on each dpp. Thus, daily postnatal exposition to low doses of LPS for 1 week resulted in a delay in formation of secondary septa, which remained up to dpp 14 in CD26− pups. The retardation was accompanied by moderate parenchymal inflammation and CD26-dependent changes in the pulmonary immune cell composition.

Presence of contractile impairment appears crucial for structural remodeling in idiopathic left bundle-branch block

BackgroundTo differentiate effects of ventricular asynchrony from an underlying hypocontractile cardiomyopathy this study aimed to enhance the understanding of functional impairment and structural remodeling in idiopathic left bundle-branch block (LBBB).We hypothesize, that functional asynchrony with septal flash volume effects alone might not entirely explain the degree of functional impairment. Hence, we suggest the presence of a superimposed contractile cardiomyopathy.MethodsIn this retrospective study, 53 patients with idiopathic LBBB were identified and matched to controls with and without cardiovascular risk factors. Cardiovascular magnetic resonance (CMR) was used to evaluate cardiac function, volumes and myocardial fibrosis using native T1 mapping and late gadolinium enhancement (LGE). Septal flash volume was assessed by CMR volumetric measurements and allowed to stratify patients with systolic dysfunction solely due to isolated ventricular asynchrony or superimposed contractile impairment.ResultsReduced systolic LV-function, increased LV-volumes and septal myocardial fibrosis were found in patients with idiopathic LBBB compared to healthy controls. LV-volumes increased and systolic LV-function declined with prolonged QRS duration. Fibrosis was typically located at the right ventricular insertion points. Subgroups with superimposed contractile impairment appeared with pronounced LV dilation and increased fibrotic remodeling compared to individuals with isolated ventricular asynchrony.ConclusionsThe presence of superimposed contractile impairment in idiopathic LBBB is crucial to identify patients with enhanced structural remodeling. This finding suggests an underlying cardiomyopathy. Future studies are needed to assess a possible prognostic impact of this entity and the development of heart failure.Trial registration: This study was retrospectively registered.

Alterations in serum iron markers in allergic fungal rhinosinusitis

Background The nasal septal body is located superior to the inferior turbinate and consists of septal cartilage thicker than the rest of septal mucosa. Object To clear the ultrastructural relation between nasal septal body and inferior turbinate using electron microscope. Patients and methods Biopsies of the nasal septal body and inferior turbinate were stained with hematoxylin–eosin and with Masson’s trichrome stain and Periodic acid–Schiff (PAS) stain. Photomicrography with morphometric analysis was used to determine the relative area proportions of each tissue type. Results Nasal septal body has a prominence of glandular tissues with a mean proportion of 19.89%, in contrast to inferior turbinate, which had 7.89%. Inferior turbinate was found to have a prominence of collagen fibers with a mean proportion of 26.58%, in contrast to the septal body, which had 13.76%. By electron microscope, epithelium of the septal body had a large number of cilia and microvilli, the junctional complex between the cells were the tightly sealed zone (tight junction), while inferior turbinate mucosa had less number of cilia than that of septal body epithelial cells. Conclusion The presence of venous sinusoids and abundant seromucinous glands in the nasal septal swell body and its histological and ultrastructural similarity to inferior turbinate should guide to surgically reduce nasal septal body volume. Keywords: inferior turbinate, nasal septal body, nasal septum, erectile tissue.

Prognostic value of cardiac magnetic resonance septal late gadolinium enhancement patterns for periaortic ventricular tachycardia ablation: Heterogeneity of the anteroseptal substrate in nonischemic cardiomyopathy

Ventricular tachycardia (VT) from the anteroseptal subtype of nonischemic cardiomyopathy has a high probability of recurrence after catheter ablation. The purpose of this study was to determine the predictive value of septal scar patterns by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) on ablation outcomes in patients with VT arising from an anteroseptal substrate. Patients with periaortic VT arising from an anteroseptal substrate with preprocedural wideband LGE-CMR were divided into 2 groups by the degree of longitudinal septal LGE extension as full-length septal (≥80% anteroposterior length) or partial septal (<80% anteroposterior length). Septal LGE volumes were quantified in those with and without VT recurrence. Among 234 patients referred for scar-related VT ablation between 2017 and 2020, 25 patients (92% male; age 64 ± 8 years) and a total of 108 VTs were analyzed. A greater number of VT morphologies were induced in patients with full-length septal LGE compared to partial septal LGE (median [interquartile range]: 5 [3-9] vs 2 [1-4]; P = .005). Patients with VT recurrence had larger septal LGE volumes compared to those without recurrence (11.4 mL [8.8-13.9] vs 4.2 mL [0-9.5]; P = .012). At median follow-up of 16 months (5-22), overall freedom from VT recurrence was 52% and significantly higher in patients with partial septal LGE than in those with full-length septal LGE (80% vs 20%; P = .005). VT originating from an anteroseptal substrate is associated with heterogeneous patterns and extent of CMR septal scar. Preprocedural imaging may substratify this challenging patient population for the propensity for multiple induced VT morphologies and recurrence after catheter ablation.

Abstract 17155: Is Aortic Annular Calcium Burden a Predictor of Post TAVR Right Ventricular Pacing?

Background: Preliminary reports have suggested the role of annular calcium in independently predicting pacemaker implantation after transcatheter aortic valve replacement (TAVR). Data regarding role of calcium in the aortic-valvular complex on pacemaker dependency is lacking. Hypothesis: Calcium volume and score in the aortic annular region predicts RV (right ventricle) pacing burden. Methods: We conducted a retrospective single-center study at our tertiary care center including patients who had new pacemaker implantation after TAVR procedure (n=47). Standard calcium scoring software was used to demarcate and quantify the calcium along the aortic cusps and subvalvular region and dichotomized into septal and non-septal based on proximity to the interventricular septum. Standard statistical tests were used for analysis with two-sided p-value &lt;0.05 considered significant. Results: The mean age was 78.6 ± 10.3 years and females were 42.6%. At baseline, 44.7% had narrow QRS complex, with 31.9% had right bundle branch block (RBBB), 8.5% had left bundle branch block (LBBB). Median Pre-TAVR QRS duration was 112 ms. Median septal and non-septal calcium score were 646 and 474 with a volume of 441 mm 3 and 327.2 mm 3 , respectively. Patients with progression to complete heart block (CHB) during index admission had significantly higher non-septal volume (650 mm 3 vs 344 mm 3 ;p=0.01) and score (892 vs 485;p=0.01) when compared to progression after discharge. Similarly, the high burden of RV pacing (&gt;40%) was associated with lower septal calcium score (989 vs 552, p= 0.03) and volume (717 mm 3 vs 385 mm 3 , p=0.03) within 3 months of TAVR. No septal or non-septal parameters were predictive of pacing burden for mid-term (3-12 months) and long-term (&gt;12 months) follow up. Septal calcium parameters were not predictive of RV pacing burden or progression to CHB. Conclusion: Quantitative calcium in the non-septal and septal regions were predictive of early progression to CHB and a higher burden of RV pacing, respectively. Larger scale studies on calcium distribution and the burden should be performed to validate our findings.

Mechanical ventilation-induced alterations of intracellular surfactant pool and blood\u2013gas barrier in healthy and pre-injured lungs

Mechanical ventilation triggers the manifestation of lung injury and pre-injured lungs are more susceptible. Ventilation-induced abnormalities of alveolar surfactant are involved in injury progression. The effects of mechanical ventilation on the surfactant system might be different in healthy compared to pre-injured lungs. In the present study, we investigated the effects of different positive end-expiratory pressure (PEEP) ventilations on the structure of the blood–gas barrier, the ultrastructure of alveolar epithelial type II (AE2) cells and the intracellular surfactant pool (= lamellar bodies, LB). Rats were randomized into bleomycin-pre-injured or healthy control groups. One day later, rats were either not ventilated, or ventilated with PEEP = 1 or 5 cmH2O and a tidal volume of 10 ml/kg bodyweight for 3 h. Left lungs were subjected to design-based stereology, right lungs to measurements of surfactant proteins (SP−) B and C expression. In pre-injured lungs without ventilation, the expression of SP-C was reduced by bleomycin; while, there were fewer and larger LB compared to healthy lungs. PEEP = 1 cmH2O ventilation of bleomycin-injured lungs was linked with the thickest blood–gas barrier due to increased septal interstitial volumes. In healthy lungs, increasing PEEP levels reduced mean AE2 cell size and volume of LB per AE2 cell; while in pre-injured lungs, volumes of AE2 cells and LB per cell remained stable across PEEPs. Instead, in pre-injured lungs, increasing PEEP levels increased the number and decreased the mean size of LB. In conclusion, mechanical ventilation-induced alterations in LB ultrastructure differ between healthy and pre-injured lungs. PEEP = 1 cmH2O but not PEEP = 5 cmH2O ventilation aggravated septal interstitial abnormalities after bleomycin challenge.

Sex-Specific Associations of Risks and Cardiac Structure and Function With Microalbumin/Creatinine Ratio in Diastolic Heart Failure.

Background: Heart failure with preserved ejection fraction (HFpEF) affects women more frequently than men. However, data on sex-specific associations of adverse health outcomes and left ventricular structure and function and with microalbuminuria in patients with HFpEF are scarce.Methods: In 1,334 participants enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) Trial, we estimated the sex-specific multivariable-adjusted risk and LV traits with urine microalbumin/creatine ratio (ACR), using Cox or linear regression.Results: In total, 604 (45.3%) were women. In multivariable-adjusted analyses, a doubling of ACR in both men and women was associated with higher posterior (+0.014 cm, p = 0.012/+0.012 cm, p = 0.033) wall thickness and left ventricular mass index (+2.55 mg/m2, p = 0.004/+2.45 mg/m2, p = 0.009), whereas was also associated with higher septal (+0.018 cm, p = 0.002) and left atrial volume index (+1.44 mL/m2, p = 0.001) in men. ACR was a key predictor of all-cause (HR, 1.11; p = 0.006) and cardiovascular (HR, 1.17; p = 0.002) death in women, whereas in men ACR was associated with HF hospitalization (HR, 1.23; p < 0.001), any hospitalization (HR, 1.06; p = 0.006), and myocardial infarction (HR, 1.19; p = 0.017). The interactions of sex with ACR were significant for hospitalization for heart failure and any hospitalization (p ≤ 0.034).Conclusions: Outcomes and cardiac structure and function in patients with HFpEF appear to be influenced by ACR that vary according to sex. In men, ACR was significant associated with LV diastolic function, hospitalization, and myocardial infarction, whereas in women was associated with mortality.

Does asymmetry in tongue anatomy affect asymmetry in tongue position? Glossectomy and control subjects

Glossectomy surgery removes part of the tongue due to cancer. The resulting anatomical asymmetries may affect motor symmetry. This study examines anatomical and positional tongue asymmetry in glossectomies and controls. The goals are to determine the extent of the anatomical asymmetries, and their effect on resting asymmetry. We expect that patients with unilateral resections will be more asymmetrical than controls, but that their midline tongue will be centered in the oral cavity (OC), because their dentition is unchanged and the tongue will rest in its familiar position. 3-D tongue volumes were extracted from high-resolution MRI data using Matlab. Tongue volumes were calculated for the whole tongue, both halves and the septum using ITK-SNAP. We bisected the OC in the sagittal plane from the mandibular symphysis to the center of the spinal cord. The tongue volume was calculated in each half of the OC. Results showed more anatomical asymmetry in the patients; seven patients and three controls had a volume difference of 3% or more between the left and right tongue. Positional measures showed that the septum was mostly in one half of the OC. When the septum volume was removed, the tongue volume distributed fairly equally in the OC.

Hidden Microatelectases Increase Vulnerability to Ventilation-Induced Lung Injury.

Mechanical ventilation of lungs suffering from microatelectases may trigger the development of acute lung injury (ALI). Direct lung injury by bleomycin results in surfactant dysfunction and microatelectases at day 1 while tissue elastance and oxygenation remain normal. Computational simulations of alveolar micromechanics 1-day post-bleomycin predict persisting microatelectases throughout the respiratory cycle and increased alveolar strain during low positive end-expiratory pressure (PEEP) ventilation. As such, we hypothesize that mechanical ventilation in presence of microatelectases, which occur at low but not at higher PEEP, aggravates and unmasks ALI in the bleomycin injury model. Rats were randomized and challenged with bleomycin (B) or not (H = healthy). One day after bleomycin instillation the animals were ventilated for 3 h with PEEP 1 (PEEP1) or 5 cmH2O (PEEP5) and a tidal volume of 10 ml/kg bodyweight. Tissue elastance was repetitively measured after a recruitment maneuver to investigate the degree of distal airspace instability. The right lung was subjected to bronchoalveolar lavage (BAL), the left lung was fixed for design-based stereology at light- and electron microscopic level. Prior to mechanical ventilation, lung tissue elastance did not differ. During mechanical ventilation tissue elastance increased in bleomycin-injured lungs ventilated with PEEP = 1 cmH2O but remained stable in all other groups. Measurements at the conclusion of ventilation showed the largest time-dependent increase in tissue elastance after recruitment in B/PEEP1, indicating increased instability of distal airspaces. These lung mechanical findings correlated with BAL measurements including elevated BAL neutrophilic granulocytes as well as BAL protein and albumin in B/PEEP1. Moreover, the increased septal wall thickness and volume of peri-bronchiolar-vascular connective tissue in B/PEEP1 suggested aggravation of interstitial edema by ventilation in presence of microatelectases. At the electron microscopic level, the largest surface area of injured alveolar epithelial was observed in bleomycin-challenged lungs after PEEP = 1 cmH2O ventilation. After bleomycin treatment cellular markers of endoplasmic reticulum stress (p-Perk and p-EIF-2α) were positive within the septal wall and ventilation with PEEP = 1 cmH2O ventilation increased the surface area stained positively for p-EIF-2α. In conclusion, hidden microatelectases are linked with an increased pulmonary vulnerability for mechanical ventilation characterized by an aggravation of epithelial injury.