scholarly journals An Integrative Study of Aortic mRNA/miRNA Longitudinal Changes in Long-Term LVAD Support

2021 ◽  
Vol 22 (14) ◽  
pp. 7414
Author(s):  
Dana Dlouha ◽  
Peter Ivak ◽  
Ivan Netuka ◽  
Sarka Benesova ◽  
Zuzana Tucanova ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Vascular Tissue ◽  
Left Ventricular ◽  
Differentially Expressed ◽  
Cell Junction ◽  
Aortic Tissue ◽  
Before And After ◽  
Long Term Impact ◽  
Lvad Support

Studying the long-term impact of continuous-flow left ventricular assist device (CF-LVAD) offers an opportunity for a complex understanding of the pathophysiology of vascular changes in aortic tissue in response to a nonphysiological blood flow pattern. Our study aimed to analyze aortic mRNA/miRNA expression changes in response to long-term LVAD support. Paired aortic samples obtained at the time of LVAD implantation and at the time of heart transplantation were examined for mRNA/miRNA profiling. The number of differentially expressed genes (Pcorr < 0.05) shared between samples before and after LVAD support was 277. The whole miRNome profile revealed 69 differentially expressed miRNAs (Pcorr < 0.05). Gene ontology (GO) analysis identified that LVAD predominantly influenced genes involved in the extracellular matrix and collagen fibril organization. Integrated mRNA/miRNA analysis revealed that potential targets of miRNAs dysregulated in explanted samples are mainly involved in GO biological process terms related to dendritic spine organization, neuron projection organization, and cell junction assembly and organization. We found differentially expressed genes participating in vascular tissue engineering as a consequence of LVAD duration. Changes in aortic miRNA levels demonstrated an effect on molecular processes involved in angiogenesis.

Ultrastructural observations of the aorta of calves implanted with a mechanical left ventricular assist device

1990 ◽  
Vol 48 (3) ◽  
pp. 834-835
Author(s):  
J P Cassella ◽  
V Salih ◽  
T R Graham
Keyword(s):  
Left Ventricular Assist Device ◽  
Ventricular Assist Device ◽  
Left Ventricular ◽  
Aortic Tissue ◽  
Assist Device ◽  
Ventricular Assist ◽  
Transmission Electron ◽  
Left Ventricular Assist ◽  
Preliminary Study

Left ventricular assist systems are being developed for eventual long term or permanent implantation as an alternative to heart transplantation in patients unsuitable for or denied the transplant option. Evaluation of the effects of these devices upon normal physiology is required. A preliminary study was conducted to evaluate the morphology of aortic tissue from calves implanted with a pneumatic Left Ventricular Assist device-LVAD. Two 3 month old heifer calves (calf 1 and calf 2) were electively explanted after 128 days and 47 days respectively. Descending thoracic aortic tissue from both animals was removed immediately post mortem and placed into karnovsky’s fixative. The tissue was subsequently processed for transmission electron microscopy (TEM). Some aortic tissue was fixed in neutral buffered formalin and processed for routine light microscopy.

scholarly journals Low-dose Vitamin K can Improve Warfarin Control in Patients on LVAD Support

2015 ◽  
Author(s):  
Daizo Tanaka ◽  
Venessa L. Kotch ◽  
Cheryl Abbas ◽  
Gordon R. Reeves ◽  
John WC Entwistle III
Keyword(s):  
Vitamin K ◽  
Low Dose ◽  
Statistical Significance ◽  
Vitamin K Antagonists ◽  
Warfarin Dose ◽  
Left Ventricular ◽  
Bleeding Complications ◽  
Thromboembolic Complications ◽  
Before And After ◽  
Lvad Support

Background Anticoagulation with oral vitamin K antagonists (VKA) is very important in patients supported on a left ventricular assist device (LVAD) to prevent thromboembolic complications. Some patients tolerate VKAs poorly and have an unstable INR as a result. It is reported that low-dose vitamin K can improve INR control in patients with an unstable INR in other clinical settings. We evaluated its safety and effectiveness in patients on LVAD support. Methods The records of all patients supported on an implantable LVAD between January, 2013 and March, 2014 were reviewed retrospectively to identify those who had received low-dose vitamin K while on warfarin. INR values and warfarin doses before and after initiation of vitamin K supplementation were compared to evaluate its effectiveness. Results There were six LVAD patients who were on low-dose vitamin K due to an unstable INR out of a total of 59 VAD patients followed as an outpatient. The standard deviation (SD) of INR decreased significantly after starting vitamin K (p=0.04) while the SD of warfarin dose did not (p=0.22). Comparing divergence from target INR, INR became significantly closer to target INR after starting vitamin K. The number of bleeding complications tended to be fewer on vitamin K, but this did not reach statistical significance (p=0.09). Conclusions Daily low-dose vitamin K supplementation can improve INR control in LVAD patients with unstable INR without increasing thromboembolic complications.

Abstract 13291: Left Ventricular Assist Device Support is Associated with Sustained Cardiac CamKII Activation and Increased MEF2

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Estibaliz Castillero ◽  
Ruiping Ji ◽  
Xiaokan Zhang ◽  
Vivian Choi ◽  
Ayesha Mannan ◽  
...  
Keyword(s):  
Left Ventricular Assist Device ◽  
Ventricular Assist Device ◽  
Cardiac Tissue ◽  
Left Ventricular ◽  
Assist Device ◽  
Ventricular Assist ◽  
Left Ventricular Assist ◽  
Before And After ◽  
Dependent Protein ◽  
Lvad Support

Background: Ca2+/calmodulin-dependent protein kinase (CaMK)II has been implicated in impaired myocardial Ca2+ signaling and may play an important role in the development of heart failure (HF). The objective of this study was to characterize CAMKII signaling in patients with HF before and after prolonged left ventricular assist device (LVAD) support. Methods: LV apex tissue pairs were collected in patients with dilated cardiomyopathy (n=10) at LVAD implantation and explantation. Normal cardiac tissue was used as control (n=4). Total protein, as well as cytoplasmic and nuclear fractions, were analyzed by Western Blot analysis. Results: The duration of LVAD support ranged from 48 to 595 days (mean = 271±54) with no patient exhibiting myocardial recovery. Total CamKIIδ levels in failing hearts were significantly higher than normal hearts and increased after LVAD, mainly due to an increase in cytoplasmic CaMKIIδC, which regulates Ca2+ handling (Table 1). Nuclear CaMKIIδB, which regulates Ca2+ gene transcription, did not change. Calmodulin remained increased in the nuclear and cytoplasmic fractions after LVAD. CaMKII autonomous, non-CaM-dependent activity, reflected by phosphorylation in Thr207, was increased pre- and post LVAD in cytoplasmic CaMKIIδC. The CaMKII-dependent myocyte enhancer factor 2 (MEF2) was increased pre- and significantly further post LVAD in the nucleus while decreased in the cytoplasm, suggesting translocation into the nucleus after LVAD support. Class IIa HDACs 4 and 5 interact with MEF2, resulting in repression of MEF2-dependent genes. Phosphorylated levels of HDAC4 and HDAC5 were increased pre- and post LVAD, which would result in activated MEF2. Conclusions: This study shows for the first time an increase of the hypertrophic factor MEF2 associated with persistent activation of CamKIIδC after prolonged LVAD support, which may have implications for cardiac remodeling during mechanical support.

Common signatures for gene expression in postnatal patients with patent arterial ducts and stented arteries

2009 ◽  
Vol 19 (4) ◽  
pp. 352-359 ◽  
Author(s):  
Peter P. Mueller ◽  
Andreas Drynda ◽  
Diane Goltz ◽  
René Hoehn ◽  
Hansjörg Hauser ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Vascular Tissue ◽  
Large Fraction ◽  
Pulmonary Arteries ◽  
Differentially Expressed ◽  
Neointimal Formation ◽  
Genome Expression ◽  
Arterial Duct ◽  
Ductal Closure ◽  
Whole Genome Expression

AbstractThe detailed molecular processes associated with postnatal remodelling of blood vessels are presently not understood. To characterize the response of the patients undergoing stenting of the patent arterial duct, we harvested samples of vascular tissue during surgical repair. Histological analysis of explanted ducts confirmed the patency of the ducts immediately after birth. As expected, a previously unstented duct that was examined 7 months after birth had become closed and ligamentous. Whole genome expression profiling of these samples showed that a large fraction, over 10%, of the gene sequences examined were expressed differentially between the samples taken from patients with open as opposed to the ligamentous duct. Interestingly, in 2 patients in whom closure was prevented by insertion of stents, one showed an expression profile that was similar to that of the patient initially having an unstented open duct, whereas the other was more closely related to the profile of the patient with a duct that had become ligamentous. Moreover, in 2 specimens obtained from patients with stented pulmonary arteries, a large fraction of the genes that were differentially expressed were identical to the pattern seen in the samples from the patients with open ducts. The gene regulation appeared to be independent of the nature of the respective malformations, and the site of implantation of the stents. These findings suggest that a set of differentially expressed genes are indicative for a transcriptional programme in neonatal remodelling of the arterial duct, which may also take place in patients in whom ductal closure is prevented by stents, or in those with stented pulmonary arteries. The differentially expressed genes included a significant number of extracellular matrix synthetic genes, and could therefore be predictive for vascular remodelling and neointimal formation.

Sick leave and disability pension before and after diagnosis of multiple sclerosis

2016 ◽  
Vol 22 (14) ◽  
pp. 1859-1866 ◽  
Author(s):  
Erik Landfeldt ◽  
Anna Castelo-Branco ◽  
Axel Svedbom ◽  
Emil Löfroth ◽  
Andrius Kavaliunas ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Sick Leave ◽  
Disability Pension ◽  
Disease Diagnosis ◽  
First Year ◽  
Final Sample ◽  
Before And After ◽  
Considerable Morbidity ◽  
Long Term Impact

Background: Multiple sclerosis (MS) is associated with considerable morbidity and serious disability, but little is known of the long-term impact of the disease on work ability. Objectives: To assess sick leave (short-term absence) and disability pension (long-term absence) before and after diagnosis of MS. Methods: Patients with MS in Sweden were identified in a nationwide disease-specific register and matched with general population controls. Sick leave and disability pension were measured before and after index (i.e. the MS diagnosis date). Results: The final sample comprised 6092 patients and 60,345 controls (mean age 39 years; 70% female). The mean annual prevalence of sick leave ranged from 12% the first year after index to 23% after 11 years among patients and from 13% to 13% among controls. Corresponding estimates for disability pension were 12% and 55% for patients and 7% and 9% for controls. Significant differences in sick leave were observed up to 15 years before index and 3 years for disability pension. Conclusion: Patients with MS in Sweden have elevated levels of sick leave and disability pension up to 15 years before disease diagnosis. Our results highlight the burden of disease on affected patients and society and underscore the substantial unmet medical need.

scholarly journals Transcriptomic analysis of PPARα-dependent alterations during cardiac hypertrophy

2008 ◽  
Vol 36 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Pascal J. H. Smeets ◽  
Heleen M. de Vogel-van den Bosch ◽  
Peter H. M. Willemsen ◽  
Alphons P. Stassen ◽  
Torik Ayoubi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Lipid Metabolism ◽  
Cardiac Hypertrophy ◽  
Signaling Pathways ◽  
Differentially Expressed Genes ◽  
Left Ventricular ◽  
Transcriptomic Analysis ◽  
Differentially Expressed ◽  
Wild Type

Peroxisome proliferator-activated receptor (PPAR)α regulates lipid metabolism at the transcriptional level and modulates the expression of genes involved in inflammation, cell proliferation, and differentiation. Although PPARα has been shown to mitigate cardiac hypertrophy, knowledge about underlying mechanisms and the nature of signaling pathways involved is fragmentary and incomplete. The aim of this study was to identify the processes and signaling pathways regulated by PPARα in hearts challenged by a chronic pressure overload by means of whole genome transcriptomic analysis. PPARα−/− and wild-type mice were subjected to transverse aortic constriction (TAC) for 28 days, and left ventricular gene expression profile was determined with Affymetrix GeneChip Mouse Genome 430 2.0 arrays containing >45,000 probe sets. In unchallenged hearts, the mere lack of PPARα resulted in 821 differentially expressed genes, many of which are related to lipid metabolism and immune response. TAC resulted in a more pronounced cardiac hypertrophy and more extensive changes in gene expression (1,910 and 312 differentially expressed genes, respectively) in PPARα−/− mice than in wild-type mice. Many of the hypertrophy-related genes were related to development, signal transduction, actin filament organization, and collagen synthesis. Compared with wild-type hypertrophied hearts, PPARα−/− hypertrophied hearts revealed enrichment of gene clusters related to extracellular matrix remodeling, immune response, oxidative stress, and inflammatory signaling pathways. The present study therefore demonstrates that, in addition to lipid metabolism, PPARα is an important modulator of immune and inflammatory response in cardiac muscle.

LONG-TERM IMPACT OF A RESTRICTIVE LABORATORY TEST ORDERING FORM ON TUMOR MARKER PRESCRIPTIONS

2003 ◽  
Vol 19 (1) ◽  
pp. 106-113 ◽  
Author(s):  
Pierre Durieux ◽  
Philippe Ravaud ◽  
Raphaél Porcher ◽  
Yvonne Fulla ◽  
Catherine-Sophie Manet ◽  
...  
Keyword(s):  
Internal Medicine ◽  
Tumor Marker ◽  
Laboratory Tests ◽  
Carbohydrate Antigen ◽  
Analysis Of Covariance ◽  
New Order ◽  
Order Form ◽  
Before And After ◽  
Long Term Impact

Objective: To evaluate the long-term impact of an intervention designed to reduce the ordering of three tumor markers frequently prescribed for gastroenterologic diseases (carcinoembryonic antigen, alpha-fetoprotein, carbohydrate antigen 19-9).Methods: A prospective study with time series analysis in a teaching hospital. Local clinical guidelines were developed and implemented through a new order form, designed as a reminder to the physician, restricting the ordering of laboratory tests. Ratios between the number of markers ordered and number of admissions were recorded during a 3-month period before and after intervention in the whole hospital and monthly on a 4-year period in two wards of the hospital (Department of Gastroenterology and Department of Internal Medicine). To evaluate the appropriateness of tumor marker orders, audits were performed on a sample of order forms, before and after (1 month and 2 years after) the implementation of the new order form.Results: The analysis of covariance showed a significant effect of the intervention in the hospital (p < .01), and in the Departments of Gastroenterology (p < .01) and Internal Medicine (p < .007). The decrease of tumor marker orders ranged from 25% (Internal Medicine Department) to 55% (whole hospital). A similar decrease was observed for the three studied markers. The appropriateness of prescriptions increased from 54.6% before to 73.6% after the implementation of the new order form, but decreased to 52.9% 2 years after intervention.Conclusions: Providing a reminder to clinicians through a specific order form represents an inexpensive and easy way to implement guidelines on use of laboratory tests.

scholarly journals Transurethral Catheterization in Early Training: The Impact of Peer-Led Mentorship

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Mohamed Mubarak ◽  
Qasim Isa ◽  
Mahmood Alsaeed ◽  
Mohamed Alalawi
Keyword(s):  
Procedural Knowledge ◽  
Junior Doctors ◽  
Confidence Levels ◽  
Transurethral Catheterization ◽  
Before And After ◽  
Long Term Impact ◽  
The Impact ◽  
Average Domain ◽  
Early Training

Introduction. Transurethral catheterization (TUC) is a common hospital procedure. According to the literature, junior doctors contribute to the majority of TUC-related injuries. Our aim is to evaluate the immediate and long-term impact of a short procedure-centric TUC workshop on junior doctor’s confidence, procedural knowledge, and ability to identify potential complications of catheterization. Materials and Methods. Intern doctors were invited to attend a one-hour workshop on TUC. A questionnaire was completed before and after the workshop. Three months later, the questionnaire was readministered to assess the workshop’s long-term impact. The questionnaire consisted of three domains. A: experience, training, and confidence levels (using 5-point Likert scales), B: procedural knowledge (the highest possible score was 10 points), and C: identification of TUC-related complications (the highest possible score was 3 points). Results. 81 interns participated and reported a confidence level of 3.03 ± 1.05 in performing a straightforward TUC. Preworkshop domain B and domain C were 3.92 ± 1.63 and 1.75 ± 0.69 points, respectively. After the workshop, reported confidence levels improved to 3.71 + 1.02 ( p < 0.05 ). Likewise, the scores in domains B and C increased significantly to 8.85 ± 1.40 ( p < 0.005 ) and 2.65 ± 0.6 ( p < 0.005 ), respectively. Three months later, the same parameters were evaluated, and confidence levels were higher than those of the preworkshop levels at 3.83 ± 0.77 ( p < 0.05 ). The average domain B score was 7.85 ± 1.88 ( p < 0.005 ), and domain C score was 2.69 ± 0.53 ( p < 0.005 ). All scores reported after three months were significantly better than the preworkshop levels ( p < 0.005 ), but there were no statistically significant differences when compared to the immediate postworkshop scores ( p > 0.05 ). Conclusion. Short peer-led TUC workshops positively impact intern doctors’ confidence levels, procedural knowledge, and identifying complications.

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