Browsing by Subject "Myocardium"

Now showing 1 - 10 of 24
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    Anisotropic Elastography for Local Passive Properties and Active Contractility of Myocardium from Dynamic Heart Imaging Sequence
    (Hindawi, 2006) Liu, Yi; Wang, Ge; Sun, L. Z.; Biomedical Engineering, Purdue School of Engineering and Technology
    Major heart diseases such as ischemia and hypertrophic myocardiopathy are accompanied with significant changes in the passive mechanical properties and active contractility of myocardium. Identification of these changes helps diagnose heart diseases, monitor therapy, and design surgery. A dynamic cardiac elastography (DCE) framework is developed to assess the anisotropic viscoelastic passive properties and active contractility of myocardial tissues, based on the chamber pressure and dynamic displacement measured with cardiac imaging techniques. A dynamic adjoint method is derived to enhance the numerical efficiency and stability of DCE. Model-based simulations are conducted using a numerical left ventricle (LV) phantom with an ischemic region. The passive material parameters of normal and ischemic tissues are identified during LV rapid/reduced filling and artery contraction, and those of active contractility are quantified during isovolumetric contraction and rapid/reduced ejection. It is found that quasistatic simplification in the previous cardiac elastography studies may yield inaccurate material parameters.
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    Apamin Does Not Inhibit Human Cardiac Na+ Current, L-type Ca2+ Current or Other Major K+ Currents
    (Public Library of Science, 2014-05-05) Yu, Chih-Chieh; Ai, Tomohiko; Weiss, James N.; Chen, Peng-Sheng; Medicine, School of Medicine
    Background: Apamin is commonly used as a small-conductance Ca2+-activated K+ (SK) current inhibitor. However, the specificity of apamin in cardiac tissues remains unclear. Objective: To test the hypothesis that apamin does not inhibit any major cardiac ion currents. Methods: We studied human embryonic kidney (HEK) 293 cells that expressed human voltage-gated Na+, K+ and Ca2+ currents and isolated rabbit ventricular myocytes. Whole-cell patch clamp techniques were used to determine ionic current densities before and after apamin administration. Results: Ca2+ currents (CACNA1c+CACNB2b) were not affected by apamin (500 nM) (data are presented as median [25th percentile;75th percentile] (from -16 [-20;-10] to -17 [-19;-13] pA/pF, P = NS), but were reduced by nifedipine to -1.6 [-3.2;-1.3] pA/pF (p = 0.008). Na+ currents (SCN5A) were not affected by apamin (from -261 [-282;-145] to -268 [-379;-132] pA/pF, P = NS), but were reduced by flecainide to -57 [-70;-47] pA/pF (p = 0.018). None of the major K+ currents (IKs, IKr, IK1 and Ito) were inhibited by 500 nM of apamin (KCNQ1+KCNE1, from 28 [20]; [37] to 23 [18]; [32] pA/pF; KCNH2+KCNE2, from 28 [24]; [30] to 27 [24]; [29] pA/pF; KCNJ2, from -46 [-48;-40] to -46 [-51;-35] pA/pF; KCND3, from 608 [505;748] to 606 [454;684]). Apamin did not inhibit the INa or ICaL in isolated rabbit ventricular myocytes (INa, from -67 [-75;-59] to -68 [-71;-59] pA/pF; ICaL, from -16 [-17;-14] to -14 [-15;-13] pA/pF, P = NS for both). Conclusions: Apamin does not inhibit human cardiac Na+ currents, L-type Ca2+ currents or other major K+ currents. These findings indicate that apamin is a specific SK current inhibitor in hearts as well as in other organs.
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    Cardiovascular Magnetic Resonance Imaging in Patients With Ibrutinib-Associated Cardiotoxicity
    (American Medical Association, 2023) Buck, Benjamin; Chum, Aaron P.; Patel, Mitkumar; Carter, Rebecca; Nawaz, Haseeb; Yildiz, Vedat; Ruz, Patrick; Wiczer, Tracy; Rogers, Kerry A.; Awan, Farrukh T.; Bhat, Seema; Guha, Avirup; Kittai, Adam S.; Simonetti, Orlando P.; Raman, Subha V.; Wallace, Grant; Sanchez, Reynaldo; Bonsu, Janice M.; Gambril, John; Haddad, Devin; Mann, James; Wei, Lai; Kola-Kehinde, Onaopepo; Byrd, John C.; Woyach, Jennifer A.; Addison, Daniel; Medicine, School of Medicine
    Importance: Ibrutinib has been associated with serious cardiotoxic arrhythmias. In preclinical models, these events are paralleled or proceeded by diffuse myocardial injury (inflammation and fibrosis). Yet whether this is seen in patients or has implications for future cardiotoxic risk is unknown. Objective: To assess the incidence and outcomes of myocardial injury among patients with ibrutinib-related cardiotoxicity. Design, setting, and participants: This cohort study included consecutive patients treated with ibrutinib from 2012 to 2019, phenotyped using cardiovascular magnetic resonance (CMR) from a large US Comprehensive Cancer Center registry. Exposures: Ibrutinib treatment for cancer control. Main outcomes and measures: The primary outcome was the presence of late gadolinium enhancement (LGE) fibrosis. The secondary outcome was the occurrence of major adverse cardiac events (MACE), defined as atrial fibrillation, heart failure, symptomatic ventricular arrhythmias, and sudden death of probable or definite ibrutinib association after CMR. We also assessed parametric-mapping subclinical fibrosis (native-T1, extracellular volume fraction) and inflammation/edema (max-T2) measures. Cardiovascular magnetic resonance measures were compared with those obtained in similar consecutive patients with cancer without ibrutinib treatment (pretreatment controls). Observed measures were also compared with similar-aged broad population rates (general-population controls) and a broader pool of cardiovascular disease (CVD) risk-matched cancer controls. Multivariable regression was used to assess the association between CMR measures and MACE. Results: Overall, 49 patients treated with ibrutinib were identified, including 33 imaged after treatment initiation (mean [SD] age, 65 [10] years, 9 [27%] with hypertension, and 23 [69.7%] with index-arrhythmias); median duration of ibrutinib-use was 14 months. The mean (SD) pretreatment native T1 was 977.0 (73.0) ms, max-T2 56.5 (4.0) ms, and 4 (13.3%) had LGE. Posttreatment initiation, mean (SD) native T1 was 1033.7 (48.2) ms, max-T2 61.5 (4.8) ms, and 17 (54.8%) had LGE (P < .001, P = .01, and P < .001, respectively, pre- vs post-ibrutinib treatment). Native T12SDs was elevated in 9 (28.6%), and max-T22SDs in 21 (63.0%), respectively. Cardiovascular magnetic resonance measures were highest in those with suspected toxic effects (P = .01 and P = .01, respectively). There was no association between traditional CVD-risk or cancer-treatment status and abnormal CMR measures. Among those without traditional CVD, 16 (58.6%) had LGE vs 38 (13.3%) in matched-controls (relative-risk, 4.8; P < .001). Over a median follow-up of 19 months, 13 (39.4%) experienced MACE. In multivariable models inclusive of traditional CVD risk factors, LGE (hazard ratio [HR], 4.9; P = .04), and native-T12SDs (HR, 3.3; P = .05) associated with higher risks of MACE. Conclusions and relevance: In this cohort study, myocardial injury was common in ibrutinib users, and its presence was associated with higher cardiotoxic risk.
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    Endurance exercise accelerates myocardial tissue oxygenation recovery and reduces ischemia reperfusion injury in mice
    (PLoS, 2014-12-04) Li, Yuanjing; Cai, Ming; Cao, Li; Qin, Xing; Zheng, Tiantian; Xu, Xiaohua; Sandvick, Taylor M.; Hutchinson, Kirk; Wold, Loren E.; Hu, Keli; Sun, Qinghua; Thomas, D. Paul; Ren, Ju; He, Guanglong; Department of Medicine, IU School of Medicine
    Exercise training offers cardioprotection against ischemia and reperfusion (I/R) injury. However, few essential signals have been identified to underscore the protection from injury. In the present study, we hypothesized that exercise-induced acceleration of myocardial tissue oxygenation recovery contributes to this protection. C57BL/6 mice (4 weeks old) were trained on treadmills for 45 min/day at a treading rate of 15 m/min for 8 weeks. At the end of 8-week exercise training, mice underwent 30-min left anterior descending coronary artery occlusion followed by 60-min or 24-h reperfusion. Electron paramagnetic resonance oximetry was performed to measure myocardial tissue oxygenation. Western immunoblotting analyses, gene transfection, and myography were examined. The oximetry study demonstrated that exercise markedly shortened myocardial tissue oxygenation recovery time following reperfusion. Exercise training up-regulated Kir6.1 protein expression (a subunit of ATP-sensitive K(+)channel on vascular smooth muscle cells, VSMC sarc-K(ATP)) and protected the heart from I/R injury. In vivo gene transfer of dominant negative Kir6.1AAA prolonged the recovery time and enlarged infarct size. In addition, transfection of Kir6.1AAA increased the stiffness and reduced the relaxation capacity in the vasculature. Together, our study demonstrated that exercise training up-regulated Kir6.1, improved tissue oxygenation recovery, and protected the heart against I/R injury. This exercise-induced cardioprotective mechanism may provide a potential therapeutic intervention targeting VSMC sarc-K(ATP) channels and reperfusion recovery.
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    The heart of the neural crest: cardiac neural crest cells in development and regeneration
    (The Company of Biologists, 2020-10-15) George, Rajani M.; Maldonado-Velez, Gabriel; Firulli, Anthony B.; Pediatrics, School of Medicine
    Cardiac neural crest cells (cNCCs) are a migratory cell population that stem from the cranial portion of the neural tube. They undergo epithelial-to-mesenchymal transition and migrate through the developing embryo to give rise to portions of the outflow tract, the valves and the arteries of the heart. Recent lineage-tracing experiments in chick and zebrafish embryos have shown that cNCCs can also give rise to mature cardiomyocytes. These cNCC-derived cardiomyocytes appear to be required for the successful repair and regeneration of injured zebrafish hearts. In addition, recent work examining the response to cardiac injury in the mammalian heart has suggested that cNCC-derived cardiomyocytes are involved in the repair/regeneration mechanism. However, the molecular signature of the adult cardiomyocytes involved in this repair is unclear. In this Review, we examine the origin, migration and fates of cNCCs. We also review the contribution of cNCCs to mature cardiomyocytes in fish, chick and mice, as well as their role in the regeneration of the adult heart.
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    Impaired cardiovascular responses to glucagon-like peptide 1 in metabolic syndrome and type 2 diabetes mellitus
    (2013-01-30) Moberly, Steven Paul; Tune, Johnathan D.; Mather, Kieren J.; Elmendorf, Jeffrey S.; Considine, Robert V.; Sturek, Michael Stephen
    Recent advancements in the management of systemic glucose regulation in obesity/T2DM include drug therapies designed to utilize components of the incretin system specifically related to glucagon-like peptide 1 (GLP-1). More recently, GLP-1 has been investigated for potential cardioprotective effects. Several investigations have revealed that acute/sub-acute intravenous administration of GLP-1 significantly reduces myocardial infarct size following ischemia/reperfusion injury and improves cardiac contractile function in the settings of coronary artery disease, myocardial ischemia/reperfusion injury, and heart failure. Despite an abundance of data indicating that intravenous infusion of GLP-1 is cardioprotective, information has been lacking on the cardiac effects of iv GLP-1 in the MetS or T2DM population. Some important questions this study aimed to address are 1) what are the direct, dose-dependent cardiac effects of GLP-1 in-vivo 2) are the cardiac effects influenced by cardiac demand (MVO2) and/or ischemia, 3) does GLP-1 effect myocardial blood flow, glucose uptake or total oxidative metabolism in human subjects, and 4) are the cardiac effects of GLP-1 treatment impaired in the settings of obesity/MetS and T2DM. Initial studies conducted in canines demonstrated that GLP-1 had no direct effect on coronary blood flow in-vivo or vasomotor tone in-vitro, but preferentially increased myocardial glucose uptake in ischemic myocardium independent of effects on cardiac contractile function or coronary blood flow. Parallel translational studies conducted in the humans and Ossabaw swine demonstrate that iv GLP-1 significantly increases myocardial glucose uptake at rest and in response to increases in cardiac demand (MVO2) in lean subjects, but not in the settings of obesity/MetS and T2DM. Further investigation in isolated cardiac tissue from lean and obese/MetS swine indicate that this impairment in GLP-1 responsiveness is related to attenuated activation of p38-MAPK, independent of alterations in GLP-1 receptor expression or PKA-dependent signaling. Our results indicate that the affects of GLP-1 to reduce cardiac damage and increase left ventricular performance may be impaired by obesity/MetS and T2DM.