Simulating the effect of sodium channel blockage on cardiac electromechanics

2019 ◽  
Vol 234 (1) ◽  
pp. 16-27
Author(s):  
Noha Shalaby ◽  
Nejib Zemzemi ◽  
Khalil Elkhodary
Keyword(s):  
Sodium Channel ◽  
Physiological Model ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Stress Model ◽  
Drug Induced ◽  
Cardiac Electromechanics ◽  
Left Ventricular Twist ◽  
Channel Blockage ◽  
Mechanical Biomarkers

There is growing interest to better understand drug-induced cardiovascular complications and to predict undesirable side effects at as early a stage in the drug development process as possible. The purpose of this paper is to investigate computationally the influence of sodium ion channel blockage on cardiac electromechanics. To do so, we implement a myofiber orientation dependent passive stress model (Holzapfel-Ogden) in the multiphysics solver Chaste to simulate an imaged physiological model of the human ventricles. A dosage of a sodium channel blocker was then applied and its inhibitory effects on the electrical propagation across ventricles were modeled. We employ the Kerckhoffs active stress model to generate electrically excited contractile behavior of myofibers. Our predictions indicate that a delay in the electrical activation of ventricular tissue caused by the sodium channel blockage translates to a delay in the mechanical biomarkers that were investigated. Moreover, sodium channel blockage was found to increase left ventricular twist. A multiphysics computational framework from the cell level to the organ level was thus used to predict the effect of sodium channel blocking drugs on cardiac electromechanics.

scholarly journals Transcriptomic analysis of the cardiac left ventricle in a rodent model of diabetic cardiomyopathy: molecular snapshot of a severe myocardial disease

2007 ◽  
Vol 28 (3) ◽  
pp. 284-293 ◽  
Author(s):  
Sarah Glyn-Jones ◽  
Sarah Song ◽  
Michael A. Black ◽  
Anthony R. J. Phillips ◽  
Soon Y. Choong ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Molecular Basis ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Myocardial Disease ◽  
Chronic Hyperglycemia ◽  
Expression Of Genes ◽  
Streptozotocin Induced Diabetes ◽  
Quantitative Verification ◽  
Disproportionate Number

Heart disease is the major cause of death in diabetes, a disorder characterized by chronic hyperglycemia and cardiovascular complications. Diabetic cardiomyopathy (DCM) is increasingly recognized as a major contributor to diastolic dysfunction and heart failure in diabetes, but its molecular basis has remained obscure, in part because of its multifactorial origins. Here we employed comparative transcriptomic methods with quantitative verification of selected transcripts by reverse transcriptase quantitative PCR to characterize the molecular basis of DCM in rats with streptozotocin-induced diabetes of 16-wk duration. Diabetes caused left ventricular disease that was accompanied by significant changes in the expression of 1,614 genes, 749 of which had functions assignable by Gene Ontology classification. Genes corresponding to proteins expressed in mitochondria accounted for a disproportionate number of those whose expression was significantly modified in DCM, consistent with the idea that the mitochondrion is a key target of the pathogenic processes that cause myocardial disease in diabetes. Diabetes also induced global perturbations in the expression of genes regulating cardiac fatty acid metabolism, whose dysfunction is likely to play a key role in the promotion of oxidative stress, thereby contributing to the pathogenesis of diabetic myocardial disease. In particular, these data point to impaired regulation of mitochondrial β-oxidation as central in the mechanisms that generate DCM pathogenesis. This study provides a comprehensive molecular snapshot of the processes leading to myocardial disease in diabetes.

scholarly journals Left ventricular twist in left ventricular noncompaction

2013 ◽  
Vol 15 (1) ◽  
pp. 48-55 ◽  
Author(s):  
F. Peters ◽  
B. K. Khandheria ◽  
E. Libhaber ◽  
N. Maharaj ◽  
C. dos Santos ◽  
...  
Keyword(s):  
Left Ventricular ◽  
Left Ventricular Noncompaction ◽  
Ventricular Noncompaction ◽  
Left Ventricular Twist ◽  
Ventricular Twist

Exercise Training Induces Left- but not Right-sided Cardiac Remodelling in Olympic Rowers

2021 ◽  
Author(s):  
Geert Kleinnibbelink ◽  
Nicole Panhuyzen-Goedkoop ◽  
Hugo Hulshof ◽  
Arie van Dijk ◽  
Keith George ◽  
...  
Keyword(s):  
Structure Function ◽  
Left Ventricular ◽  
Cardiac Remodelling ◽  
Training Volume ◽  
Ventricular Structure ◽  
Left Ventricular Twist ◽  
Weekly Training ◽  
Elite Rowers ◽  
Ventricular Twist ◽  
The Impact

AbstractWhilst the athlete’s heart has been extensively described, less work has focused on the potential for elite athletes to demonstrate further cardiac remodelling upon an increase in training volume. Moreover, little work explored potential side-specific cardiac remodelling. Therefore, we examined the impact of an increase in training volume across 9-months in elite rowers on left- and right-sided cardiac structure, function and mechanics (i. e. longitudinal, radial and circumferential strain, twist and strain-volume loops). As part of the preparations to the 2012 Olympic Games, twenty-seven elite rowers (26.4±3.7years, 19 male) underwent echocardiography prior to and post (9 months) an increase in training volume (24 to 30–35 h weekly). Training increased left ventricular structure, including wall thickness, diameter, volume, mass and LV twist (all p<0.05). Female rowers demonstrated larger adaptation in left ventricular diameter and mass compared to male rowers (both p<0.05). No changes were observed in other measures of left ventricular function in both sexes (all p>0.05). The 9-month intervention showed no change in right ventricular/atrial structure, function or mechanics (all p>0.05). In conclusion, our data revealed that 9-month increased training volume in elite rowers induced left-sided (but not right-sided) structural remodelling, concomitant with an increase in left ventricular twist, with some changes larger in women.

scholarly journals Global Longitudinal Strain or Left Ventricular Twist and Torsion? Which Correlates Best with Ejection Fraction?

2017 ◽  
Author(s):  
Marcio Silva Miguel Lima ◽  
Hector R Villarraga ◽  
Maria Cristina Donadio Abduch ◽  
Marta Fernandes Lima ◽  
Cecilia Beatriz Bittencourt Viana Cruz ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Longitudinal Strain ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Left Ventricular Twist ◽  
Ventricular Twist

Left Ventricular Twist and Ventricular-Arterial Coupling in Hypertensive Patients

2014 ◽  
Vol 31 (10) ◽  
pp. 1274-1282 ◽  
Author(s):  
Hong-Won Shin ◽  
Hyungseop Kim ◽  
Jeong-Eun Lee ◽  
In-Cheol Kim ◽  
Hyuck-Jun Yoon ◽  
...  
Keyword(s):  
Left Ventricular ◽  
Hypertensive Patients ◽  
Left Ventricular Twist ◽  
Ventricular Twist

scholarly journals Anthracycline-Induced Cardiotoxicity in Young Cancer Patients: The Role of Carnitine

2016 ◽  
Vol 68 (Suppl. 3) ◽  
pp. 10-14 ◽  
Author(s):  
Saro H. Armenian
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Cancer Patients ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Childhood Cancer Survivors ◽  
Chronic Health Condition ◽  
Cardiovascular Complications ◽  
Left Ventricular

While the increased rates of survival in childhood cancers have increased progressively in recent decades, many childhood cancer survivors will have at least one chronic health condition within 40 years of age. In this regard, cardiovascular complications have emerged as a leading cause of long-term morbidity and mortality in long-term survivors of childhood cancer, likely due to exposure to anthracycline chemotherapy, and outcomes in patients with anthracycline-related cardiomyopathy remain poor. Some progress has been made in understanding the mechanisms at the basis of anthracycline-related cardiomyopathy, which appear to involve generation of reactive oxygen species, leading to mitochondrial dysfunction, followed by myocyte apoptosis and maladaptive left ventricular remodeling. Even if several guidelines currently exist for monitoring cancer patients treated with cardiotoxic therapies who are at high risk for heart failure, much work remains to be done in finding reliable markers for screening for cardiac dysfunction. Studies from our group have identified alterations in L-carnitine in cancer survivors. While additional investigations are needed, preliminary studies suggest a role for carnitine in primary prevention (during treatment) and secondary prevention (to improve function after treatment).

scholarly journals Cardiovascular morbidity and mortality in patients treated with hemodialysis: Epidemiological analysis

2008 ◽  
Vol 65 (12) ◽  
pp. 893-900 ◽  
Author(s):  
Dejan Petrovic ◽  
Biljana Stojimirovic
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Mortality Rate ◽  
Cardiovascular Mortality ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Cardiovascular Morbidity ◽  
Morbidity And Mortality ◽  
Cardiovascular Morbidity And Mortality ◽  
Lv Mass

Background/Aim. Cardiovascular diseases are the leading cause of death in patients treated with hemodialysis (HD). The annual cardiovascular mortality rate in these patients is 9%. Left ventricular (LV) hypertrophy, ischemic heart disease and heart failure are the most prevalent cardiovascular causes of death. The aim of this study was to assess the prevalence of traditional and nontraditional risk factors for cardiovascular complications, to assess the prevalence of cardiovascular complications and overall and cardiovascular mortality rate in patients on HD. Methods. We investigated a total of 115 patients undergoing HD for at least 6 months. First, a cross-sectional study was performed, followed by a two-year follow-up study. Beside standard biochemical parameters, we also determined cardiac troponins and echocardiographic parameters of LV morphology and function (LV mass index, LV fractional shortening, LV ejection fraction). The results were analyzed using the Student's t test and Mann-Whitney U test. Results. The patients with adverse outcome had significantly lower serum albumin (p < 0.01) and higher serum homocystein, troponin I and T, and LV mass index (p < 0.01). Hyperhomocysteinemia, anemia, hypertriglyceridemia and uncontrolled hypertension had the highest prevalence (86.09%, 76.52%, 43.48% and 36.52%, respectively) among all investigated cardiovascular risk factors. Hypertrophy of the LV was presented in 71.31% of the patients and congestive heart failure in 8.70%. Heart valve calcification was found in 48.70% of the patients, pericardial effusion in 25.22% and disrrhythmia in 20.87% of the investigated patients. The average annual overall mortality rate was 13.74%, while average cardiovascular mortality rate was 8.51%. Conclusion. Patients on HD have high risk for cardiovascular morbidity and mortality.

scholarly journals Drug-Induced Heart Failure (Part 2: Mechanisms of Development, Clinical Signs, Differential Diagnosis, Risk Factors, Treatment and Prevention)

2020 ◽  
Vol 8 (2) ◽  
pp. 57-65
Author(s):  
O. D. Ostroumova ◽  
I. V. Goloborodova
Keyword(s):  
Heart Failure ◽  
Beta Blockers ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Left Ventricular ◽  
Clinical Syndrome ◽  
Channel Blockers ◽  
Drug Induced ◽  
Treatment And Prevention ◽  
Developing Heart

Heart failure is a complex clinical syndrome caused by an impaired pumping function of the heart muscle, etiologically associated with cardiovascular disease and, in the vast majority of cases, requiring complex therapeutic regimens and simultaneous prescription of several drugs. To date, we know several classes of drugs (including those used for heart failure) which can induce development/progression of heart failure in both patients with left ventricular dysfunction, and in patients who do not have cardiovascular diseases. The aim of the study was to analyse and systematize data on development mechanisms, as well as methods of prevention and treatment of drug-induced heart failure when using diff erent groups of drugs. It has been established that drug-induced heart failure is most often associated with the use of calcium channel blockers (verapamil, diltiazem, nifedipine), beta-blockers, antiarrhythmic drugs (disopyramide, fl ecainide, propafenone, amiodarone, ibutilide, dofetilide, dronedarone), anthracyclines (doxorubicin) and other antitumor drugs (trastuzumab, bevacizumab, infl iximab), hypoglycemic drugs (thiazolidinediones, saxagliptin, alogliptin), and nonsteroidal anti-infl ammatory drugs, including selective cyclooxygenase-2 inhibitors. The study revealed various mechanisms of heart failure development following drug treatment. In some patients, heart failure development is associated with the cardiotoxic eff ect of a particular drug, in others with adverse eff ects on hemodynamics. Much depends on risks of developing heart failure, including specifi c risks attributable to groups of drugs and individual drugs. The identifi cation of drugs that can contribute to the development/ progression of heart failure, and possible clinical manifestations of drug-induced heart failure, as well as provision of timely information to physicians, and engagement of clinical pharmacologists with the aim of optimizing treatment of patients can facilitate timely diagnosis, treatment and prevention of drug-induced heart failure. 

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