scholarly journals Ultrastructural Adaptation of the Cardiomyocyte to Chronic Mitral Regurgitation

2021 ◽  
Vol 8 ◽  
Author(s):  
Daniella Corporan ◽  
Ana Segura ◽  
Muralidhar Padala

Introduction: Mitral regurgitation (MR) imposes volume overload on the left ventricle (LV) and elevates wall stress, triggering its adverse remodeling. Pronounced LV dilation, minimal wall thinning, and a gradual decline in cardiac ejection fraction (EF) are observed. The structural changes in the myocardium that define these gross, organ level remodeling are not known. Cardiomyocyte elongation and slippage have both been hypothesized, but neither are confirmed, nor are the changes to the cardiomyocyte structure known. Using a rodent model of MR, we used immunohistochemistry and transmission electron microscopy (TEM) to describe the ultrastructural remodeling of the cardiomyocyte.Methods: Twenty-four male Sprague-Dawley rats (350–400 g) were assigned to two groups: group (1) rats induced with severe MR (n = 18) and group (2) control rats that were healthy and age and weight matched (n = 6). MR was induced in the beating heart using a 23-G ultrasound-guided, transapical needle to perforate the anterior mitral leaflet, and the rats were followed to 2, 10, and 20 weeks (n = 6/time-point). Echocardiography was performed to quantify MR severity and to measure LV volume and function at each time-point. Explanted myocardial tissue were examined with TEM and immunohistochemistry to investigate the ultrastructural changes.Results: MR induced rapid and significant increase in end-diastolic volume (EDV), with a 50% increase by 2 weeks, compared with control. Rise in end-systolic volume (ESV) was more gradual; however, by 20 weeks, both EDV and ESV in MR rats were increased by 126% compared with control. A significant decline in EF was measured at 10 weeks of MR. At the ultrastructural level, as early as 2 weeks after MR, cardiomyocyte elongation and increase in cross-sectional area were observed. TEM depicted sarcomere shortening, with loss of Z-line and I-band. Desmin, a cytoskeletal protein that is uniformly distributed along the length of the cardiomyocyte, was disorganized and localized to the intercalated disc, in the rats induced with MR and not in the controls. In the rats with MR, the linear registry of the mitochondrial arrangement along the sarcomeres was lost, with mitochondrial fragmentation, aggregation around the nucleus, and irregularities in the cristae.Discussion: In the setting of chronic mitral regurgitation, LV dilatation occured by cardiomyocyte elongation, which manifests at the subcellular level as distinct ultrastructural alterations of the sarcomere, cytoskeleton, and mitochondria. Since the cytoskeleton not only provides tensegrity but has functional consequences on myocyte function, further investigation into the impact of cytoskeletal remodeling on progressive heart failure or recovery of function upon correcting the valve lesion are needed.

2021 ◽  
Vol 12 (2) ◽  
pp. 1272-1275
Author(s):  
Angu Bala Ganesh K S V ◽  
Sujeet Shekhar Sinha ◽  
Kesavi Durairaj ◽  
Abdul Sahabudeen K

Naphthalene is a bicyclic aromatic constituent commonly used in different domestic and marketable applications comprising soil fumigants, lavatory scent disks and mothballs. Accidentally, workers, children and animals are exposed to naphthalene mothballs, so there is a need to study the pathology behind this chemical toxicity. The current study was carried out to assess the ultra structural changes of basolateral amygdaloid nuclei in the Sprague Dawley rats brain in association to naphthalene toxicity. The toxicity model group was administered with naphthalene (200 and 400mg) using corn oil as a vehicle for 28 days. The post delayed toxicity of naphthalene high dose ingestion was also assessed in rats. After the experimental period, the brain tissue was processed to observe the ultra structural changes using a transmission electron microscope. The alterations in cell organelles, nuclei damage, mitochondrial swelling, chromatin condensation suggested naphthalene induced damage in the neurons of the basolateral amygdala of the brain in the toxicity model group. These experimental trials provide information about the alert of mothball usage in the home and identify risks linked with accidental exposure and misuse.


2011 ◽  
Vol 89 (10) ◽  
pp. 743-751 ◽  
Author(s):  
Adil El Midaoui ◽  
Calin Lungu ◽  
Hui Wang ◽  
Lingyun Wu ◽  
Caroline Robillard ◽  
...  

This study sought to determine the impact of α-lipoic acid (LA) on superoxide anion (O2•–) production and peroxisome proliferator-activated receptor-α (PPARα) expression in liver tissue, plasma free fatty acids (FFA), and aortic remodeling in a rat model of insulin resistance. Sprague–Dawley rats (50–75 g) were given either tap water or a drinking solution containing 10% D-glucose for 14 weeks, combined with a diet with or without LA supplement. O2•– production was measured by lucigenin chemiluminescence, and PPAR-α expression by Western blotting. Cross-sectional area (CSA) of the aortic media and lumen and number of smooth muscle cells (SMC) were determined histologically. Glucose increased systolic blood pressure (SBP), plasma levels of glucose and insulin, and insulin resistance (HOMA index). All of these effects were attenuated by LA. Whereas glucose had no effect on liver PPAR-α protein level, it decreased plasma FFA. LA decreased the aortic and liver O2•– production, body weight, and plasma FFA levels in control and glucose-treated rats. Liver PPAR-α protein levels were increased by LA, and negatively correlated with plasma FFA. Medial CSA was reduced in all glucose-treated rats, and positively correlated with plasma FFA but not with SBP or aortic O2•– production. Glucose also reduced aortic lumen area, so that the media-to-lumen ratio remained unchanged. The ability of LA to lower plasma FFA appears to be mediated, in part, by increased hepatic PPAR-α expression, which may positively affect insulin resistance. Glucose-fed rats may serve as a unique model of aortic atrophic remodeling in hypertension and early metabolic syndrome.


1990 ◽  
Vol 72 (4) ◽  
pp. 626-633 ◽  
Author(s):  
Marc R. Mayberg ◽  
Tomohisa Okada ◽  
Don H. Bark

✓ A porcine model was developed to allow quantitative assessment of morphological changes in cerebral arteries after subarachnoid hemorrhage and to determine the significance of structural changes in producing arterial narrowing. Whole blood was selectively applied to the middle cerebral artery (MCA) of seven pigs. After 10 days, vessels were perfusion-fixed and examined by light and transmission electron microscopy and immunohistochemistry. The MCA's exposed to whole blood for 10 days showed prominent luminal narrowing associated with profound ultrastructural changes affecting all layers of the vessel wall. Morphometric analysis, however, demonstrated that significant reductions in the luminal cross-sectional area (−55.8% ± 12.5%, p < 0.005) and increases in radial wall thickness (75.1% ± 10.5%, p < 0.005) were associated with only minimal increase in the cross-sectional area of the vessel wall (12.5% ± 15%,p < 0.025). By stereological analysis, the volume density of individual components of the arterial wall was unchanged in MCA's exposed to blood. Vessels exposed to blood showed a 44% reduction in smooth-muscle cell immunoreactive actin and increased collagen in the extracellular matrix of the vessel wall. These data suggest that structural changes in cerebral arteries after subarachnoid hemorrhage do not directly contribute to vessel narrowing through increases in wall mass. Nevertheless, such changes may reflect pathological mechanisms which act to augment prolonged vasoconstriction or inhibit the maintenance of normal vascular tone.


1992 ◽  
Vol 167 (1) ◽  
pp. 91-117 ◽  
Author(s):  
M. B. Rheuben

The ultrastructural changes associated with the early stages of degeneration of the larval mesothoracic muscle fibers of Manduca sexta were examined during the prepupal period and on the first day after ecdysis. Over this 5 day period, the muscle fibers decrease in cross-sectional area but increase in apparent surface area compared to the dimensions of early fifth-instar fibers. Large numbers of electron-dense granules or droplets are formed and extruded from the muscle cytoplasm into the hemolymph; this process may account for some of the decrease in muscle fiber mass and may represent a developmental mechanism for recycling nutrients. As the fibers shrink, the thick basal lamina is thrown into folds. Phagocytic hemocytes (granulocytes) congregate in clusters over the surface of the degenerating fibers and appear to remove specifically the basal lamina. The timely removal of the thick larval basal lamina may be essential for subsequent fusion of myoblasts to the residual larval myofibers. The contractile elements within the degenerating muscle fibers become disorganized but are not dysfunctional at the end of the first 12 h after the pupal ecdysis. Tracheoles withdraw from intimate contact with each muscle fiber in its clefts and T-tubules and associate in groups adjacent to it. Mitochondria appear to be degenerating. These structural changes are concurrent with a previously observed decline in resting potential and suggest that a significant change in the electrical properties of the muscle fibers should be expected as well.


2021 ◽  
pp. 026988112110326
Author(s):  
Anna Powell ◽  
Harry Sumnall ◽  
Cecil Kullu ◽  
Lynn Owens ◽  
Catharine Montgomery

Background: Dependent alcohol drinkers exhibit differences in the structure and function of the brain, and impairments in cognitive function, including executive functions (EFs). Less is known about the impact of non-dependent but hazardous use (that which raises the risk of harm), and it is also unclear to what extent executive impairments in this cohort affect real-world function. The current study examines the relationship between alcohol use, EF and alcohol-related problems, in the general population. Methods: A between-groups cross-sectional design assessed EF across two levels of drinking; hazardous (Alcohol Use Disorders Identification Test (AUDIT) score of ⩾8) and non-hazardous. Alcohol drinkers ( n = 666; 136 male; 524 female; six not disclosed; aged 28.02 ± 10.40 years) completed validated questionnaires online assessing subjective EF, alcohol use and alcohol-related problems. Results: Organisation, Strategic Planning, Impulse Control and overall function were significantly impaired in hazardous drinkers. Furthermore, the effect of alcohol on EF, partially mediated the relationship between alcohol use and alcohol-related problems. Conclusion: Hazardous drinking was associated with lower subjective EF, and this mediated the effect of alcohol on alcohol-related problems. This may be due to changes in prefrontal brain regions, which could indicate greater risk for the development of alcohol dependence (AD). Future research should use additional means to assess EF in hazardous drinkers, including recovery of function, development of AD and the relationship between cognition and alcohol-related daily problems.


2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S32-S33
Author(s):  
Brian M Kelter ◽  
Audrey E Wolfe ◽  
Callie Abouzeid ◽  
Nicole S Gibran ◽  
Radha K Holavanahalli ◽  
...  

Abstract Introduction The COVID-19 pandemic has had widespread effects on healthcare and society at large. There are limited data on the impact of the pandemic on the long-term recovery of the burn survivor. This study aims to compare physical and psychosocial outcomes of the burn survivor population before and during the COVID-19 pandemic. Methods Data from the Burn Model System National Database (2015-present) were analyzed. Data were divided into pre- and during-pandemic groups (before and after March 1st, 2020). Outcomes were compared at four cross-sectional time points: 6, 12, 24, and 60 months after burn injury. The following patient reported outcome measures were examined: SF-12 Health Survey, PROMIS-29, Post-Traumatic Growth Indicator, Community Integration Questionnaire, Patient Civilian Checklist, Satisfaction with Life Scale, Burn Specific Health Scale, NeuroQOL Stigma, 4-D Itch, and CAGE Questionnaire (drug/alcohol misuse). Given the cross-sectional design, potential differences in clinical and demographic characteristics were examined for each group at each time point. Adjusted mean outcome scores at each time point were compared between groups using a two stage multi-variable regression model with propensity score matching. For each time point, subjects from each group were matched. The propensity score was calculated using the following matching variables: gender, age, race, ethnicity, etiology, length of stay, and burn size. The mean score difference of outcomes within each matched sample was examined. Results Sample sizes varied by time point with a range from 420 at 6 months to 94 at 60 months. The during-COVID group comprised 10% of the total sample size. There were no significant differences in demographic and clinical characteristics between the groups at any time point. There were no significant differences between the groups in adjusted mean outcome scores across the different time points. Conclusions This preliminary examination showed no differences in myriad long-term outcomes at multiple time points after injury among burn survivors before and during the start of the COVID-19 pandemic. The results may suggest an element of resilience, however given the sample size and cross-sectional limitations further investigation is required to better understand the impact of COVID-19 on the burn population.


2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
P. F. Felisaz ◽  
G. Maugeri ◽  
V. Busi ◽  
R. Vitale ◽  
F. Balducci ◽  
...  

The aim of this study was to assess with MRI morphometric ultrastructural changes in nerves affected by diabetic peripheral neuropathy (DPN). We used an MR micro-neurography imaging protocol and a semiautomated technique of tissue segmentation to visualize and measure the volume of internal nerve components, such as the epineurium and nerve fascicles. The tibial nerves of 16 patients affected by DPN and of 15 healthy volunteers were imaged. Nerves volume (NV), fascicles volume (FV), fascicles to nerve ratio (FNR), and nerves cross-sectional areas (CSA) were obtained. In patients with DPN the NV was increased and the FNR was decreased, as a result of an increase of the epineurium (FNR in diabetic neuropathy 0,665; in controls 0,699, p=0,040). CSA was increased in subjects with DPN (12,84 mm2 versus 10,22 mm2, p=0,003). The FV was increased in patients with moderate to severe DPN. We have demonstrated structural changes occurring in nerves affected by DPN, which otherwise are assessable only with an invasive biopsy. MR micro-neurography appears to be suitable for the study of microscopic changes in tibial nerves of diabetic patients.


2021 ◽  
pp. 112067212110356
Author(s):  
Nazife Aşıkgarip ◽  
Emine Temel ◽  
Ahmet Kıvrak ◽  
Kemal Örnek

Purpose: To assess the impact of systemic hypertension on the choroidal structure and choroidal vascularity index (CVI). Methods: This prospective cross-sectional study comprised 50 eyes of 50 treatment-naive hypertensive patients and 50 eyes of 50 healthy subjects. Choroidal thickness (CT) was measured in the subfoveal region, 1500 µm nasal to the fovea, and 1500 µm temporal to the fovea. Binarization of the enhanced depth-optical coherence tomography images was performed with Image-J software. The CT, choroidal area (CA), luminal area (LA), and CVI were compared statistically. Results: The mean subfoveal, nasal, and temporal CT were decreased in the patient group (p 0.003, 0.026, and 0.001, respectively). The mean CA, LA, and CVI were decreased in the patient group in comparison to controls ( p = 0.047, 0.009, and 0.016 respectively). The correlation between the subfoveal CT and systolic blood pressure was significant ( r = −0.450, p < 0.001). There was a significant correlation between the systolic blood pressure and CVI ( r = −0.401, p < 0.001). Conclusion: The significant decrease in the structural parameters and CVI show that choroid is affected in patients with treatment-naive hypertension.


2020 ◽  
Vol 2 (1) ◽  
pp. 233-244
Author(s):  
Victor Ogneru ◽  
Stelian Stancu

Abstract The paper analyzes the relationship between the total tax amount paid by the Romanian companies and several indicators of size, financial performance, and capital structure to identify whether there is an impact of these indicators on the tax potential and to assess the impact of the tax burden on the performance of companies as well. The total tax amount is viewed on the one hand as a tax burden when it is used as an independent variable, and as tax potential when it is used as a dependent variable. To assess these relationships, we applied cross-sectional regression models for each year of analysis, 2014-2018, using balance sheet data from the entire population of Romanian companies. In literature, is questioned only the relationship between tax burden and economic performance. Our study emphasizes the link between tax potential and some characteristics of the companies. We have identified, also, the determinants of return of equity in the case of Romanian companies. Overall, the data reveal major structural changes during the period of analysis. This movement did not affect the tax potential, but the performance of undertakings. Our findings show that it is necessary to rethink economic and tax policies.


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