scholarly journals Pharmacologic therapy for engraftment arrhythmia induced by transplantation of human cardiomyocytes

2021 ◽  
Vol 16 (10) ◽  
pp. 2473-2487
Author(s):  
Kenta Nakamura ◽  
Lauren E. Neidig ◽  
Xiulan Yang ◽  
Gerhard J. Weber ◽  
Danny El-Nachef ◽  
...  
2012 ◽  
Vol 9 (1) ◽  
pp. 57-60 ◽  
Author(s):  
Gina G Mentzer ◽  
Alex J Auseon

Heart failure (HF) affects more than 5 million people and has an increasing incidence and cost burden. Patients note symptoms of dyspnea and fatigue that result in a decreased quality of life, which has not drastically improved over the past decades despite advances in therapies. The assessment of exercise capacity can provide information regarding patient diagnosis and prognosis, while doubling as a potential future therapy. clinically, there is acceptance that exercise is safe in hf and can have a positive impact on morbidity and quality of life, although evidence for improvement in mortality is still lacking. specific prescriptions for exercise training have not been developed because many variables and confounding factors have prevented research trials from demonstrating an ideal regimen. Physicians are becoming more aware of the indices and goals for hf patients in exercise testing and therapy to provide comprehensive cardiac care. it is further postulated that a combination of exercise training and pharmacologic therapy may eventually provide the most benefits to those suffering from hf.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Pelin A. Golforoush ◽  
Priyanka Narasimhan ◽  
Patricia P. Chaves-Guerrero ◽  
Elsa Lawrence ◽  
Gary Newton ◽  
...  

2021 ◽  
Vol 14 (8) ◽  
pp. 748
Author(s):  
Péter P. Nánási ◽  
Balázs Horváth ◽  
Fábián Tar ◽  
János Almássy ◽  
Norbert Szentandrássy ◽  
...  

Due to the limited availability of healthy human ventricular tissues, the most suitable animal model has to be applied for electrophysiological and pharmacological studies. This can be best identified by studying the properties of ion currents shaping the action potential in the frequently used laboratory animals, such as dogs, rabbits, guinea pigs, or rats, and comparing them to those of human cardiomyocytes. The authors of this article with the experience of three decades of electrophysiological studies, performed in mammalian and human ventricular tissues and isolated cardiomyocytes, summarize their results obtained regarding the major canine and human cardiac ion currents. Accordingly, L-type Ca2+ current (ICa), late Na+ current (INa-late), rapid and slow components of the delayed rectifier K+ current (IKr and IKs, respectively), inward rectifier K+ current (IK1), transient outward K+ current (Ito1), and Na+/Ca2+ exchange current (INCX) were characterized and compared. Importantly, many of these measurements were performed using the action potential voltage clamp technique allowing for visualization of the actual current profiles flowing during the ventricular action potential. Densities and shapes of these ion currents, as well as the action potential configuration, were similar in human and canine ventricular cells, except for the density of IK1 and the recovery kinetics of Ito. IK1 displayed a largely four-fold larger density in canine than human myocytes, and Ito recovery from inactivation displayed a somewhat different time course in the two species. On the basis of these results, it is concluded that canine ventricular cells represent a reasonably good model for human myocytes for electrophysiological studies, however, it must be borne in mind that due to their stronger IK1, the repolarization reserve is more pronounced in canine cells, and moderate differences in the frequency-dependent repolarization patterns can also be anticipated.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Ruppert ◽  
Z.S Onodi ◽  
P Leszek ◽  
V.E Toth ◽  
G Koncsos ◽  
...  

Abstract Background Inflammation and cytokine release have been implicated in the pathogenesis of chronic heart failure (CHF). Of particular interest, Canakinumab, a monoclonal antibody against interleukin-1b (IL-1β), had provided benefit against cardiovascular events, suggesting that blockade of IL-1β secretion and signaling might be a promising new therapeutic target. Although, recent studies have provided evidence that inflammasome activation is the main contributor to IL-1β maturation, the role of inflammasome activation in CHF remains unknown. Objective Therefore, we aimed to assess inflammasome activation in myocardial samples from end-stage failing hearts. Methods Inflammasome activation was assessed by immunoblotting in left ventricular myocardial specimens harvested from patients with end-stage CHF. Furthermore, immunoblot measurements were also performed on translational animal models of CHF (e.g. rat models of permanent coronary artery ligation and transverse aortic constriction). Left ventricular monocyte and macrophage infiltration was detected by immunohistochemistry. To investigate the molecular background of inflammasome activation, a series of cell culture experiments were performed on AC16 human cardiomyocytes and THP-1 human monocytic cell lines. Results Out of the 4 major inflammasome sensors tested, expression of the inflammasome protein absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) increased in human CHF while the NLRP1 and NLRP3 (NLR family, pyrin domain containing 1 and 3) inflammasome showed no change. A similar expression pattern in AIM2 and NLRC4 was also noted in CHF animal models. Furthermore, robust infiltration of Iba1+ monocytes/macrophages was observed in human failing hearts as well as in different animal models of CHF. In vitro AIM2 inflammasome activation, as induced by transfection with double-stranded DNA [poly(deoxyadenylic-deoxythymidylic)] was reduced significantly by the pharmacological blockade of pannexin-1 channels. Conclusions AIM2 and NLRC4 inflammasome activation might contribute to chronic inflammation in CHF. Our findings suggest that pannexin-1 channels might be a promising novel target to reduce inflammasome activation. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): NVKP_16-1-2016-0017


2020 ◽  
pp. 089719002097962
Author(s):  
Edna Patatanian ◽  
David R. Nguyen

Objectives: To review the pharmacology, efficacy, and safety of Brexanolone and define its role in the treatment of postpartum depression. Date Sources: A MEDLINE/PubMed search was conducted (1980-May 2020) using the following keywords: postpartum depression, antidepressants, pharmacologic therapy, drug therapy, and brexanolone to identify relevant articles. Study Selection/Data Extraction: Literature search was limited to human studies published in the English language. Phase I, II, and III studies evaluating the pharmacology, efficacy, safety of brexanolone for postpartum depression were included. Bibliographies of relevant articles evaluating postpartum depression and treatment were reviewed for additional citations and background information. Data Synthesis: Brexanolone is a soluble, proprietary, injectable formulation of allopregnanolone, a neuroactive steroid that modulates neuronal excitability. Allopregnanolone levels increase during pregnancy and decrease substantially after birth. These fluctuations have profound effects on anxiety and depression. Three clinical trials established the efficacy and safety of brexanolone in the treatment of postpartum depression. In all 3 trials, brexanolone had an acceptable safety profile and was well tolerated. The most common adverse effects were loss of consciousness, sedation, dry mouth, headache, dizziness, and flushing. Due to sudden loss of consciousness and excessive sedation, continuous pulse oximetry is recommended. Conclusion: Brexanolone has a novel mechanism of action and appears to be safe and effective for the treatment of moderate to severe postpartum depression. At present, high cost, serious adverse effects, and restricted access may limit its use in clinical practice.


2021 ◽  
Vol 11 (2) ◽  
pp. 185-189
Author(s):  
Eric Omar Then ◽  
Tyler Grantham ◽  
Michell Lopez ◽  
Madhavi Reddy ◽  
Vinaya Gaduputi

Esophagitis dissecans superficialis (EDS) is a rare and underdiagnosed esophageal lesion characterized by sloughing of the esophageal mucosa that has been associated with medications, various autoimmune disorders, and exposure to some chemical irritants. Anatomically, EDS is most commonly seen in the middle and distal thirds of the esophagus. When present, EDS is best treated by discontinuing the offending agent and initiating pharmacologic therapy with proton pump inhibitors. Steroids may also be effective if the etiology is autoimmune in nature. Our case highlights a 65-year-old female diagnosed with EDS after incidental ingestion of hair dye containing resorcinol and para-phenylenediamine (PPD).


Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1153
Author(s):  
Shih-Lung Cheng ◽  
Ching-Hsiung Lin

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease that is associated with significant morbidity and mortality, giving rise to an enormous social and economic burden. The Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease (GOLD) report is one of the most frequently used documents for managing COPD patients worldwide. A survey was conducted across country-level members of Asia-Pacific Society of Respiratory (APSR) for collecting an updated version of local COPD guidelines, which were implemented in each country. This is the first report to summarize the similarities and differences among the COPD guidelines across the Asia-Pacific region. The degree of airflow limitation, assessment of COPD severity, management, and pharmacologic therapy of stable COPD will be reviewed in this report.


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