scholarly journals Posterior lymph heart function in two species of anurans: analysis based on both in vivo pressure-volume relationships by conductance manometry and ultrasound

2010 ◽  
Vol 213 (21) ◽  
pp. 3710-3716 ◽  
Author(s):  
D. A. Crossley ◽  
S. S. Hillman
Keyword(s):  
Heart Function ◽  
Lymph Heart

scholarly journals Drosophila Preparation and Longitudinal Imaging of Heart Function In Vivo Using Optical Coherence Microscopy (OCM)

10.3791/55002 ◽  
2016 ◽  
Author(s):  
Jing Men ◽  
Jason Jerwick ◽  
Penghe Wu ◽  
Mingming Chen ◽  
Aneesh Alex ◽  
...  
Keyword(s):  
Heart Function ◽  
Optical Coherence ◽  
Optical Coherence Microscopy ◽  
Longitudinal Imaging

Abstract 131: C-kit+ Cells Generated From Failed Heart Do Not Improve Failed Heart Function

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Liudmila Zakharova ◽  
Hikmet Nural ◽  
James R Nimlos ◽  
Snjezana Popovic ◽  
Lorraine Feehery ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Ventricle ◽  
Diastolic Pressure ◽  
Heart Function ◽  
Smooth Muscle Actin ◽  
Functional Improvement ◽  
Gene Expressions ◽  
Coronary Vein ◽  
Mesenchymal Transition

A pilot clinical study using autologous c-Kit+ cells showed improvement in cardiac functions in congestive heart failure (CHF), however, it is unclear if c-Kit+ cells isolated from CHF hearts are equally as potent as cells from controls. To test the potency of CHF c-Kit+ cells, myocardial infarction (MI) was created by permanent ligation of the left anterior descending coronary artery. Six weeks after MI, animals with left ventricle end-diastolic pressure (LVEDP) ≥20 mmHg and scar size ≥30% of left ventricle (LV) were designated as CHF rats. We found that CHF atrial explants generated less c-Kit+ cells compared to shams (15.7% vs. 11% sham vs. CHF). CHF c-Kit+ cells exhibited elevated levels of epicardial to mesenchymal transition markers, including Snail (2.5 fold) and Pai1 (3 fold), while the expression level of epithelial marker, E-cadherin was 3 fold lower in CHF c-Kit+ cells. Moreover, CHF c-Kit+ cells exhibited reduced gene expressions of pluripotency markers; 2.1 fold decrease in Nanog and 4.5 fold decrease in Sox 2 compared to sham cells. To evaluate the potency of the c-Kit+ cells, 1 x 10 6 cells isolated from CHFs or shams were delivered to 3 weeks post-MI CHF hearts. Cells were pre-labeled with GFP to enable their tracing in vivo and delivered to the infarcted myocardium via left coronary vein by a retrograde coronary sinus cell infusion (RCI). RCI delivery resulted in a cell distribution of LV (30%), right atrium (30%) and right ventricle (20%), while only 10% of cells were found in a left atrium. Three weeks after cells delivery, rats transplanted with sham c-Kit+ cells showed improved LVEDP (29.4 ± 6 vs. 11.7 ± 3.5 mmHg, CHF vs. CHF+ sham c-Kit+ cells) and a rise in peak rate of pressure (dPdt max) (3988 ± 520 vs. 5333 ± 597 mmHg/s). In contrast, no functional improvement was detected in rats transplanted with CHF c-Kit+ cells. Histological analysis demonstrated that transplanted c-Kit+/GFP+ cells were mostly incorporated into blood vessels and co-localized with endothelial marker vWf, and α-smooth muscle actin. Our results showed that left coronary vein is an efficient route for c-Kit+ cell delivery and that c-Kit+ cells isolated from CHF rats are less potent when transplanted in chronic heart failure rat model compared to those isolated from control.

Cellular and functional defects in a mouse model of heart failure

2000 ◽  
Vol 279 (6) ◽  
pp. H3101-H3112 ◽  
Author(s):  
Giovanni Esposito ◽  
L. F. Santana ◽  
Keith Dilly ◽  
Jader Dos Santos Cruz ◽  
Lan Mao ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adrenergic Receptor ◽  
Heart Function ◽  
Imaging Techniques ◽  
Single Cells ◽  
Structural Protein ◽  
Muscle Lim Protein ◽  
Intracellular Ca ◽  
Whole Heart

Heart failure and dilated cardiomyopathy develop in mice that lack the muscle LIM protein (MLP) gene (MLP−/−). The character and extent of the heart failure that occurs in MLP−/− mice were investigated using echocardiography and in vivo pressure-volume (P-V) loop measurements. P-V loop data were obtained with a new method for mice (sonomicrometry) using two pairs of orthogonal piezoelectric crystals implanted in the endocardial wall. Sonomicrometry revealed right-shifted P-V loops in MLP−/−mice, depressed systolic contractility, and additional evidence of heart failure. Cellular changes in MLP−/− mice were examined in isolated single cells using patch-clamp and confocal Ca2+ concentration ([Ca2+]) imaging techniques. This cellular investigation revealed unchanged Ca2+ currents and Ca2+ spark characteristics but decreased intracellular [Ca2+] transients and contractile responses and a defect in excitation-contraction coupling. Normal cellular and whole heart function was restored in MLP−/− mice that express a cardiac-targeted transgene, which blocks the function of β-adrenergic receptor (β-AR) kinase-1 (βARK1). These data suggest that, despite the persistent stimulus to develop heart failure in MLP−/− mice (i.e., loss of the structural protein MLP), downregulation and desensitization of the β-ARs may play a pivotal role in the pathogenesis. Furthermore, this work suggests that the inhibition of βARK1 action may prove an effective therapy for heart failure.

scholarly journals Physical Activity and Inhibition of ACE Additively Modulate ACE/ACE-2 Balance in Heart Failure in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Urszula Tyrankiewicz ◽  
Mariola Olkowicz ◽  
Piotr Berkowicz ◽  
Magdalena Jablonska ◽  
Ryszard T. Smolenski ◽  
...  
Keyword(s):  
Physical Activity ◽  
Heart Failure ◽  
Heart Function ◽  
Combined Treatment ◽  
Training Group ◽  
Cardiac Performance ◽  
Angiotensin Converting Enzyme Inhibition ◽  
Ang Ii ◽  
Spontaneous Physical Activity

Angiotensin-converting enzyme inhibition (ACE-I) and physical activity favorably modulate the ACE/ACE-2 balance. However, it is not clear whether physical activity and ACE-I could synergistically modulate ACE/ACE-2 balance in the course of heart failure (HF). Here, we studied the effects of combined spontaneous physical activity and ACE-I–based treatment on angiotensin (Ang) pattern and cardiac function in a mouse model of HF (Tgαq*44). Tgαq*44 mice with advanced HF (at the age of 12 months) were running spontaneously in a running wheel (exercise training group, ExT) and/or were treated with ACE inhibitor (ACE-I, perindopril, 10 mg/kg) for 2 months. Angiotensin profile was characterized by an LC-MS/MS-based method. The cardiac performance was assessed in vivo by MRI. Ang-(1–7)/Ang II ratio in both plasma and the aorta was significantly higher in the combined treatment group than the ACE-I group or ExT alone, suggesting the additive favorable effects on ACE-2/Ang-(1–7) and ACE/Ang II axes’ balance induced by a combination of ACE-I with ExT. The basal cardiac performance did not differ among the experimental groups of Tgαq*44 mice. We demonstrated additive changes in ACE/ACE-2 balance in both plasma and the aorta by spontaneous physical activity and ACE-I treatment in Tgαq*44 mice. However, these changes did not result in an improvement of failing heart function most likely because the disease was at the end-stage. Ang-(1–7)/Ang II balance represents a valuable biochemical end point for monitoring therapeutic intervention outcome in heart failure.

scholarly journals Network pharmacology-based identification of major component of Angelica sinensis and its action mechanism for the treatment of acute myocardial infarction

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Xiaowei Niu ◽  
Jingjing Zhang ◽  
Jinrong Ni ◽  
Runqing Wang ◽  
Weiqiang Zhang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Er Stress ◽  
Heart Function ◽  
Network Pharmacology ◽  
Angelica Sinensis ◽  
Peroxisome Proliferator ◽  
Multiple Targets

Background: To decipher the mechanisms of Angelica sinensis for the treatment of acute myocardial infarction (AMI) using network pharmacology analysis. Methods: Databases were searched for the information on constituents, targets, and diseases. Cytoscape software was used to construct the constituent–target–disease network and screen the major targets, which were annotated with the DAVID (Database for Annotation, Visualization and Integrated Discovery) tool. The cardioprotective effects of Angelica sinensis polysaccharide (ASP), a major component of A. sinensis, were validated both in H9c2 cells subjected to simulated ischemia by oxygen and glucose deprivation and in rats with AMI by ligation of the left anterior coronary artery. Results: We identified 228 major targets against AMI injury for A. sinensis, which regulated multiple pathways and hit multiple targets involved in several biological processes. ASP significantly decreased endoplasmic reticulum (ER) stress-induced cell death both in vitro and in vivo. In ischemia injury rats, ASP treatment reduced infarct size and preserved heart function. ASP enhanced activating transcription factor 6 (ATF6) activity, which improved ER-protein folding capacity. ASP activated the expression of p-AMP-activated protein kinase (p-AMPK) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α). Additionally, ASP attenuated levels of proinflammatory cytokines and maintained a balance in the oxidant/antioxidant levels after AMI. Conclusion:In silico analysis revealed the associations between A. sinensis and AMI through multiple targets and several key signaling pathways. Experimental data indicate that ASP protects the heart against ischemic injury by activating ATF6 to ameliorate the detrimental ER stress. ASP’s effects could be mediated via the activation of AMPK-PGC1α pathway.

scholarly journals Therapeutic Inhibition of Acid Sensing Ion Channel 1a Recovers Heart Function After Ischemia-Reperfusion Injury

Circulation ◽  
2021 ◽  
Author(s):  
Meredith A. Redd ◽  
Sarah E. Scheuer ◽  
Natalie J. Saez ◽  
Yusuke Yoshikawa ◽  
Han Sheng Chiu ◽  
...  
Keyword(s):  
Ion Channel ◽  
Reperfusion Injury ◽  
Electromechanical Coupling ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Genetic Ablation ◽  
Organ Level

Background: Ischemia-reperfusion injury (IRI) is one of the major risk factors implicated in morbidity and mortality associated with cardiovascular disease. During cardiac ischemia, the build-up of acidic metabolites results in decreased intracellular and extracellular pH that can reach as low as 6.0-6.5. The resulting tissue acidosis exacerbates ischemic injury and significantly impacts cardiac function. Methods: We used genetic and pharmacological methods to investigate the role of acid sensing ion channel 1a (ASIC1a) in cardiac IRI at the cellular and whole organ level. Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) as well as ex vivo and in vivo models of IRI were used to test the efficacy of ASIC1a inhibitors as pre- and post-conditioning therapeutic agents. Results: Analysis of human complex trait genetics indicate that variants in the ASIC1 genetic locus are significantly associated with cardiac and cerebrovascular ischemic injuries. Using hiPSC-CMs in vitro and murine ex vivo heart models, we demonstrate that genetic ablation of ASIC1a improves cardiomyocyte viability after acute IRI. Therapeutic blockade of ASIC1a using specific and potent pharmacological inhibitors recapitulates this cardioprotective effect. We used an in vivo model of myocardial infarction (MI) and two models of ex vivo donor heart procurement and storage as clinical models to show that ASIC1a inhibition improves post-IRI cardiac viability. Use of ASIC1a inhibitors as pre- or post-conditioning agents provided equivalent cardioprotection to benchmark drugs, including the sodium-hydrogen exchange inhibitor zoniporide. At the cellular and whole organ level, we show that acute exposure to ASIC1a inhibitors has no impact on cardiac ion channels regulating baseline electromechanical coupling and physiological performance. Conclusions: Collectively, our data provide compelling evidence for a novel pharmacological strategy involving ASIC1a blockade as a cardioprotective therapy to improve the viability of hearts subjected to IRI.

Abstract 144: Post-myocardial Infarction Therapeutics Using Cardiovascular Progenitor Cells (PC) Derived from Induced Pluripotent Stem Cells (iPSC)

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Yigang Wang
Keyword(s):  
Cardiac Function ◽  
Heart Function ◽  
Vessel Density ◽  
Protective Effects ◽  
Paracrine Factors ◽  
Beneficial Effects ◽  
The Third ◽  
Simplex Virus ◽  
Patch Group

Objective: We sought to assess the cardiac protective effects after MI of (1) PC differentiated directly into cardiomyocytes (CM) and endothelial cells (EC) to the site of injury, or (2) paracrine factors released from PC. Methods: These concepts were evaluated by using iPSC-derived PC genetically modified to express the herpes simplex virus thymidine kinase (TK) under the control of cardiomyocyte (NCX1) or endothelial cell (VE-cadherin) specific promoters. PC expressing the TK permitted ablation at the first week or the third week by iv ganciclovir (GCV). If GCV applied at the first week, but not at the third week, altered cardiac function, we would conclude that myocardial contractile recovery depends on CM and EC-derived from iPSC. If the beneficial effects on cardiac function persisted after GCV was given at the third week, we would surmise that the PC effect was via by a paracrine action. MI created by ligation of LAD, the cell patch with PC was applied to the scarred myocardium. Rats were treated with GCV at 1 or 3 weeks to ablate implanted PC. Echocardiography, vessel density, and histological analysis were used to obtain endpoints for this study. Result: In vivo : The levels of IGF-1α and VEGF released from ischemic tissues were significant higher in the cell patch group. Heart function, infarction size, and vessel density were significantly improved after cell patch treatment. However, this beneficial effect on cardiac function was completely abolished in the group given GCV at week 1, but only partially abolished in the group given GCV at week 3 compared to the untreated cell patch group. Conclusions: Taken together, these data support our conclusion that iPSC-derived cardiovascular lineages (CM and EC) contribute directly to an improved cardiac performance and attenuated remodeling, and that paracrine factors also play a supporting role in the restoration of heart function after MI.

MTORC1-Regulated Metabolism Controlled by TSC2 Limits Cardiac Reperfusion Injury

2021 ◽  
Author(s):  
Christian U Oeing ◽  
Seungho Jun ◽  
Sumita Mishra ◽  
Brittany Dunkerly-Eyring ◽  
Anna Chen ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Ex Vivo ◽  
Heart Function ◽  
Acid Oxidation ◽  
Chain Acyl ◽  
Myocardial Substrate ◽  
Gain Loss ◽  
Whole Heart ◽  
Mtorc1 Activation

Rationale: The mechanistic target of rapamycin complex-1 (mTORC1) controls metabolism and protein homeostasis, and is activated following ischemic reperfusion (IR) injury and by ischemic preconditioning (IPC). However, studies vary as to whether this activation is beneficial or detrimental, and its influence on metabolism after IR is little studied. A limitation of prior investigations is their use of broad gain/loss of mTORC1 function, mostly applied prior to ischemic stress. This can be circumvented by regulating one serine (S1365) on tuberous sclerosis complex (TSC2) to achieve bi-directional mTORC1 modulation but only with TCS2-regulated co-stimulation. Objective: We tested the hypothesis that reduced TSC2 S1365 phosphorylation protects the myocardium against IR and IPC by amplifying mTORC1 activity to favor glycolytic metabolism. Methods and Results: Mice with either S1365A (TSC2 SA ; phospho-null) or S1365E (TSC2 SE ; phosphomimetic) knock-in mutations were studied ex vivo and in vivo. In response to IR, hearts from TSC2 SA mice had amplified mTORC1 activation and improved heart function compared to WT and TSC2 SE hearts. The magnitude of protection matched IPC. IPC requited less S1365 phosphorylation, as TSC2 SE hearts gained no benefit and failed to activate mTORC1 with IPC. IR metabolism was altered in TSC2 SA , with increased mitochondrial oxygen consumption rate and glycolytic capacity (stressed/maximal extracellular acidification) after myocyte hypoxia-reperfusion. In whole heart, lactate increased and long-chain acyl-carnitine levels declined during ischemia. The relative IR protection in TSC2 SA was lost by lowering glucose in the perfusate by 36%. Adding fatty acid (palmitate) compensated for reduced glucose in WT and TSC2 SE but not TSC2 SA which had the worst post-IR function under these conditions. Conclusions: TSC2-S1365 phosphorylation status regulates myocardial substrate utilization, and its decline activates mTORC1 biasing metabolism away from fatty acid oxidation to glycolysis to confer protection against IR. This pathway is also engaged and reduced TSC2 S1365 phosphorylation required for effective IPC.

scholarly journals AGED MICE ARE SUSCEPTIBLE TO CARDIAC HYPERTROPHY AFTER 1 WEEK OF CONSUMING A HIGH SUGAR DIET

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S108-S108
Author(s):  
Ana P Valencia ◽  
Jeremy Whitson ◽  
Rudolph Stuppard ◽  
Gustavo Valencia ◽  
Peter Rabinovitch ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Heart Function ◽  
The Elderly ◽  
Saline Control ◽  
H2o2 Production ◽  
Sugar Consumption ◽  
Short Term ◽  
Increased Risk ◽  
Old Mice

Abstract Over 80% of American adults exceed their daily recommended intake of sugar (<10% kcal). While habitual sugar consumption is associated with an increased risk for diabetes and cardiovascular disease, less is known about the effects of short-term sugar consumption on metabolic health, particularly in the elderly. The purpose of this study was to test whether aged hearts are more susceptible to pathology following a short-term high sucrose (HS) diet. Specific goals were to: A) determine the effects of a 1-week HS diet exposure on the hearts of 5 month-old and 24 month-old mice; and B) test if the mitochondrial targeted peptide SS-31 can protect against HS-diet induced effects. Male CB6F1 mice were placed either on standard chow or HS diet after 1 week of receiving saline (control) or SS-31 through osmotic pumps. Heart function was assessed in vivo through echocardiography before and after treatments. One week of HS induced significant cardiac hypertrophy in the old mice compared to age-matched chow controls. Treatment with SS-31 prevented this HS induced hypertrophy. Young hearts were smaller than in the old, but size was unaffected by diet or SS-31. We observed no effect of HS (with or without SS-31) on respiration or H2O2 production in isolated mitochondria from hearts using high-resolution respirometry. These data indicate that only 1-week exposure to HS diet is enough to exacerbate cardiac hypertrophy in aging mice, but factors other than heart mitochondrial ROS may mediate this effect.

scholarly journals Assessing the Efficacy of Dietary Selenomethionine Supplementation in the Setting of Cardiac Ischemia/Reperfusion Injury

Antioxidants ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 546 ◽  
Author(s):  
Leila Reyes ◽  
David P. Bishop ◽  
Clare L. Hawkins ◽  
Benjamin S. Rayner
Keyword(s):  
Cardiac Myocyte ◽  
Hypochlorous Acid ◽  
Ischemia Reperfusion Injury ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Cytosolic Calcium ◽  
Cardiac Ischemia ◽  
Cellular Damage

Oxidative stress is a major hallmark of cardiac ischemia/reperfusion (I/R) injury. This partly arises from the presence of activated phagocytes releasing myeloperoxidase (MPO) and its production of hypochlorous acid (HOCl). The dietary supplement selenomethionine (SeMet) has been shown to bolster endogenous antioxidant processes as well as readily react with MPO-derived oxidants. The aim of this study was to assess whether supplementation with SeMet could modulate the extent of cellular damage observed in an in vitro cardiac myocyte model exposed to (patho)-physiological levels of HOCl and an in vivo rat model of cardiac I/R injury. Exposure of the H9c2 cardiac myoblast cell line to HOCl resulted in a dose-dependent increase in necrotic cell death, which could be prevented by SeMet supplementation and was attributed to SeMet preventing the HOCl-induced loss of mitochondrial inner trans-membrane potential, and the associated cytosolic calcium accumulation. This protection was credited primarily to the direct oxidant scavenging ability of SeMet, with a minor contribution arising from the ability of SeMet to bolster cardiac myoblast glutathione peroxidase (GPx) activity. In vivo, a significant increase in selenium levels in the plasma and heart tissue were seen in male Wistar rats fed a diet supplemented with 2 mg kg−1 SeMet compared to controls. However, SeMet-supplementation demonstrated only limited improvement in heart function and did not result in better heart remodelling following I/R injury. These data indicate that SeMet supplementation is of potential benefit within pathological settings where excessive HOCl is known to be generated but has limited efficacy as a therapeutic agent for the treatment of heart attack.

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