scholarly journals Cardiac Function is not Susceptible to Moderate Disassembly of Mitochondrial Respiratory Supercomplexes

2020 ◽  
Vol 21 (5) ◽  
pp. 1555 ◽  
Author(s):  
Xavier R. Chapa-Dubocq ◽  
Keishla M. Rodríguez-Graciani ◽  
Roberto A. Guzmán-Hernández ◽  
Sehwan Jang ◽  
Paul S. Brookes ◽  
...  
Keyword(s):  
Electron Transport ◽  
Cardiac Function ◽  
Heart Function ◽  
Polyacrylamide Gel Electrophoresis ◽  
Secondary Alcohol ◽  
Physiological Role ◽  
High Energy ◽  
Control Group ◽  
Ros Production ◽  
Mitochondrial Respiratory

Mitochondrial respiratory chain supercomplexes (RCS), particularly, the respirasome, which contains complexes I, III, and IV, have been suggested to participate in facilitating electron transport, reducing the production of reactive oxygen species (ROS), and maintaining the structural integrity of individual electron transport chain (ETC) complexes. Disassembly of the RCS has been observed in Barth syndrome, neurodegenerative and cardiovascular diseases, diabetes mellitus, and aging. However, the physiological role of RCS in high energy-demanding tissues such as the heart remains unknown. This study elucidates the relationship between RCS assembly and cardiac function. Adult male Sprague Dawley rats underwent Langendorff retrograde perfusion in the presence and absence of ethanol, isopropanol, or rotenone (an ETC complex I inhibitor). We found that ethanol had no effects on cardiac function, whereas rotenone reduced heart contractility, which was not recovered when rotenone was excluded from the perfusion medium. Blue native polyacrylamide gel electrophoresis revealed significant reductions of respirasome levels in ethanol- or rotenone-treated groups compared to the control group. In addition, rotenone significantly increased while ethanol had no effect on mitochondrial ROS production. In isolated intact mitochondria in vitro, ethanol did not affect respirasome assembly; however, acetaldehyde, a byproduct of ethanol metabolism, induced dissociation of respirasome. Isopropanol, a secondary alcohol which was used as an alternative compound, had effects similar to ethanol on heart function, respirasome levels, and ROS production. In conclusion, ethanol and isopropanol reduced respirasome levels without any noticeable effect on cardiac parameters, and cardiac function is not susceptible to moderate reductions of RCS.

The Effects of Carvedilol on Cardiac Function and the AKT/XIAP Signaling Pathway in Diabetic Cardiomyopathy Rats

Cardiology ◽  
2016 ◽  
Vol 136 (3) ◽  
pp. 204-211 ◽  
Author(s):  
Wencheng Zheng ◽  
Xiaoming Shang ◽  
Chunlai Zhang ◽  
Xiang Gao ◽  
Barry Robinson ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Signaling Pathway ◽  
Diabetic Cardiomyopathy ◽  
Interstitial Fibrosis ◽  
High Energy ◽  
Control Group ◽  
Tunel Staining ◽  
Myocardial Inflammation ◽  
Western Blots ◽  
Male Wistar Rats

Objectives: Diabetic cardiomyopathy (DCM) is characterized by cardiac dysfunction, myocardial inflammation, interstitial fibrosis and cardiomyocytes apoptosis. The present study aimed to investigate the effects of carvedilol on cardiac function and the AKT/XIAP signaling pathway in DCM rats. Methods: Male Wistar rats were randomly divided into 3 groups: the control group, diabetic mellitus (DM) group and DM with carvedilol treatment group. DM rats were induced by streptozotocin accompanied by high energy intake. Carvedilol was orally administered at a dose of 10 mg/kg/day. After 16 weeks, the interrelated blood data were detected by biochemical analysis. Cardiac function was evaluated by echocardiography and the serum NT-proBNP level. The changes of myocardium ultrastructural and fibrosis were determined by electron microscopy and Masson's staining. Apoptotic cells were examined by TUNEL staining and interrelated proteins were measured by immunohistochemical and Western blots. Results: Rats in the DM group showed significant serum elevation of glucose, cholesterol, triglyceride, NT-proBNP, IL-1β and TNF-α, along with decreased cardiac function. Moreover, in the DM group, the levels of myocardial apoptosis and fibrosis were all increased accompanied by upregulation of caspase-3 and downregulation of phos-AKT and phos-XIAP, whereas carvedilol treatment prevented or reversed all the changes without influencing plasma levels of glucose, cholesterol and triglyceride. Conclusions: The AKT/XIAP signaling pathway may be involved in DCM. Carvedilol can improve cardiac function, possibly not only by upregulating the AKT/XIAP antiapoptotic signaling pathway and subsequently attenuating myocardial fibrosis, but also through suppressing the myocardial inflammation response.

Abstract 14195: Impact of Leukocyte Filtration and Leukocyte Modulation on Recovery of Heart Function After Prolonged Cardiac Arrest Treated With ECPR in a Porcine Model

Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
Jensyn VanZalen ◽  
Takahiro Nakashima ◽  
Annie Phillips ◽  
Joseph Hill ◽  
Alyssa Enciso ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Cardiac Function ◽  
Heart Function ◽  
Randomized Study ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Swine Model ◽  
Extracorporeal Cardiopulmonary Resuscitation ◽  
Ventricular Ejection Fraction

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) improves survival of patients with prolonged cardiac arrest (CA) that is refractory to standard CPR and ACLS. It has been proposed that ECPR accentuates inflammation after CA, potentially limiting its effectiveness. The benefits of leukocyte filters or leukocyte-modulating devices in conjunction with ECPR have not been studied. Hypothesis: When paired with ECPR, inflammation-modulating devices targeting leukocytes may improve recovery of cardiac function after prolonged cardiac arrest. Methods: In a randomized study, 24 swine (40±5kg) underwent 8min of untreated ventricular fibrillation CA followed by CPR with mechanical chest compressions and impedance threshold device for 30 min (total arrest time = 38min), immediately followed by 8h of ECPR with heparin anticoagulation and temperature maintained at 33°C. Group 1 (n=8) had standard ECPR system (control), Group 2 (n=8) had a leukocyte filter device (LF) added to the ECPR circuit, an and Group 3 (n=8) had a leukocyte modulation device (LMOD) added to the ECPR circuit. Recovery of cardiac function was measured using a cardiac resuscitablity score (CRS) and left ventricular ejection fraction (LVEF) via transthoracic echocardiography. Data was collected at baseline (prior CA) and after 8h of ECPR. Data analysis: single-factor ANOVA test (p<0.05 significance). Results: There were no statically significant differences between the groups in CRS (Control = 3.3 ± 2.4, LF = 4.0 ± 2.8, LMOD = 2.1 ± 2.6; p=0.37) or LVEF (Control = 59% ± 27%, LF = 49% ± 29% LMOD = 34% ± 38%: p=0.34) at 8 hours after ECPR initiation (Table 1). Discussion: In this swine model of prolonged cardiac arrest treated with ECPR, addition of a leukocyte filter or leukocyte modulation device to the ECPR circuit did not improve recovery of cardiac function during the first 8 hours after initiating ECPR.

Attenuated cardiac function degradation in ex vivo pig hearts

2019 ◽  
Vol 43 (3) ◽  
pp. 173-179
Author(s):  
Benjamin Kappler ◽  
Sjoerd van Tuijl ◽  
Bülent Ergin ◽  
Louis Fixsen ◽  
Marco Stijnen ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Ex Vivo ◽  
Heart Function ◽  
Blood Parameters ◽  
Diagnostic Tools ◽  
Control Group ◽  
Isolated Hearts ◽  
Cardiac Hemodynamics ◽  
Cardiac Pump Function

Isolated hearts offer the opportunity to evaluate heart function, treatments, and diagnostic tools without in vivo factor interference. However, the early loss of cardiac function and edema occur over time and do limit the duration of the experiment. This research focuses on delaying these limitations using optimal blood control. This study examines whether blood conditioning by means of the combination of blood predilution and hemodialysis can significantly reduce cardiac function degradation. Slaughterhouse porcine hearts were revived in the PhysioHeart™ platform to restore physiological cardiac performance. Twelve hearts were divided into a control group and a dialysis group; in the latter group, hemodialysis was attached to the blood reservoir. Cardiac hemodynamics and blood parameters were recorded and evaluated. Blood conditioning significantly reduced the loss of cardiac pump function (control group vs dialysis group, −14.9 ± 6.3%/h vs −9.7 ± 2.7%/h) and loss of cardiac output (control group vs dialysis group, −11.8 ± 3.4%/h vs −5.9 ± 2.0%/h). Hemodialysis resulted in physiological and stable blood parameters, whereas in the control group ions reached pathological values, while interstitial edema still occurred. The combination of blood predilution and hemodialysis significantly attenuated ex vivo cardiac function degradation and delayed the loss of cardiac hemodynamics. We hypothesized that besides electrolyte and metabolic control, the hemodialysis-accompanied increase in hematocrit resulted in improved oxygen transport. This could have temporarily compensated the deleterious effect of an increased oxygen-diffusion distance due to edema in the dialysis group and resulted in less progression of cell decay. Clinically validated measures delaying edema might improve the effectiveness of the PhysioHeart™ platform.

Abstract 1281: Human Adipose Tissue-derived Stem Cells Potently Preserve Cardiac Function Resulting From Permanently Induced Myocardial Ischemia

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Liying Cai ◽  
Brian H Johnstone ◽  
Todd G Cook ◽  
Keith L March
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Cardiac Function ◽  
Heart Function ◽  
Human Adipose Tissue ◽  
Functional Improvement ◽  
Saline Control ◽  
Control Group

Background The use of stem cells has gained much interest as a potential therapeutic approach for repair of damage caused by a variety of cardiac insults. We and others have demonstrated the ability of pluripotent adipose-derived stem cells (ASCs), to promote repair in ischemic skeletal tissues. Here we demonstrate that ASCs also stimulate a robust functional improvement following acute myocardial infarction (MI) in rats. Methods and Results ASCs were harvested from human subcutaneous adipose tissue. ASCs were characterized in vitro before in vivo testing. Growth and metabolic activity of human microvascular endothelial cells (HMVEC) cultured in growth-factor deficient minimal medium (MM) increased 1.7-fold when supplemented with a 1:1 mixture of ASC CM ( p <0.01). Sprout formation by HMVECs and migration of endothelial progenitor cell (EPC) was enhanced by 2.1 and 2.0-fold, repectively, when ASC CM was added to MM ( p <0.01). Following demonstration of potency in vitro, the ASCs were evaluated for the ability to protect and rescue ischemic myocardium in an athymic nude rat following permanent ligation of the proximal LAD region. Immediately after ligation 10 6 ASCs in 100 μl saline or carrier alone was injected into 2 sites of the peri-infarct region, then at 4 and 28 d heart function was evaluated echocardiography using a Visualsonics Vivo770. ASC-treated rats consistently exhibited better cardiac function at 1 month compared to the saline control group. LV ejection fraction of the ASC group was 56 ± 7% (mean ± SEM) vs 37 ± 3% for the control (p<0.04). Fractional shortening was 32 ± 5% (ASC) vs 19 ± 2% (p<0.04). LV volumes both at end-diastolic and end-systolic stages were lower in ASC group (311 ± 17 μl and 139 ± 21 μl, respectively) than saline group (391 ± 30 μl and 249 ± 27 μl) (p<0.03). Anterior wall thinning was attenuated in ASC group (1.6 ± .08 mm vs 1.2 ± .2, at end-diastole, p<0.03). Post-mortem histological analysis demonstrated that ASC treated hearts had lower fibrosis (26 ± 6% vs 34 ± 6%; p<0.05). Conclusion We have demonstrated that ASCs have great potential as a cell therapy to preserve heart function following ischemic insult. Given the abundant source of ASCs, therapies with these cells have a higher potential for widespread adoption compared to more rare cell types.

scholarly journals Effect of defibrillation on the performance of an implantable vagus nerve stimulation system

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Imad Libbus ◽  
Scott R. Stubbs ◽  
Scott T. Mazar ◽  
Scott Mindrebo ◽  
Bruce H. KenKnight ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Pulse Generator ◽  
High Energy ◽  
Implantable Pulse Generator ◽  
Defibrillation Pulse ◽  
Stimulation System

Abstract Background Vagus Nerve Stimulation (VNS) delivers Autonomic Regulation Therapy (ART) for heart failure (HF), and has been associated with improvement in cardiac function and heart failure symptoms. VNS is delivered using an implantable pulse generator (IPG) and lead with electrodes placed around the cervical vagus nerve. Because HF patients may receive concomitant cardiac defibrillation therapy, testing was conducted to determine the effect of defibrillation (DF) on the VNS system. Methods DF testing was conducted on three ART IPGs (LivaNova USA, Inc.) according to international standard ISO14708-1, which evaluated whether DF had any permanent effects on the system. Each IPG was connected to a defibrillation pulse generator and subjected to a series of high-energy pulses. Results The specified series of pulses were successfully delivered to each of the three devices. All three IPGs passed factory electrical tests, and interrogation confirmed that software and data were unchanged from the pre-programmed values. No shifts in parameters or failures were observed. Conclusions Implantable VNS systems were tested for immunity to defibrillation, and were found to be unaffected by a series of high-energy defibrillation pulses. These results suggest that this VNS system can be used safely and continue to function after patients have been defibrillated.

scholarly journals Autophagy facilitates type I collagen synthesis in periodontal ligament cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tomomi Nakamura ◽  
Motozo Yamashita ◽  
Kuniko Ikegami ◽  
Mio Suzuki ◽  
Manabu Yanagita ◽  
...  
Keyword(s):  
Periodontal Ligament ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Periodontal Diseases ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Physiological Role ◽  
Type I ◽  
Periodontal Tissue ◽  
Pdl Cells

AbstractAutophagy is a lysosomal protein degradation system in which the cell self-digests its intracellular protein components and organelles. Defects in autophagy contribute to the pathogenesis of age-related chronic diseases, such as myocardial infarction and rheumatoid arthritis, through defects in the extracellular matrix (ECM). However, little is known about autophagy in periodontal diseases characterised by the breakdown of periodontal tissue. Tooth-supportive periodontal ligament (PDL) tissue contains PDL cells that produce various ECM proteins such as collagen to maintain homeostasis in periodontal tissue. In this study, we aimed to clarify the physiological role of autophagy in periodontal tissue. We found that autophagy regulated type I collagen synthesis by elimination of misfolded proteins in human PDL (HPDL) cells. Inhibition of autophagy by E-64d and pepstatin A (PSA) or siATG5 treatment suppressed collagen production in HPDL cells at mRNA and protein levels. Immunoelectron microscopy revealed collagen fragments in autolysosomes. Accumulation of misfolded collagen in HPDL cells was confirmed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis. E-64d and PSA treatment suppressed and rapamycin treatment accelerated the hard tissue-forming ability of HPDL cells. Our findings suggest that autophagy is a crucial regulatory process that facilitates type I collagen synthesis and partly regulates osteoblastic differentiation of PDL cells.

scholarly journals Optimization of Lutein Recovery from Tetraselmis suecica by Response Surface Methodology

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 182
Author(s):  
Kang Hyun Lee ◽  
Ye Won Jang ◽  
Hansol Kim ◽  
Jang-Seu Ki ◽  
Hah Young Yoo
Keyword(s):  
Response Surface Methodology ◽  
Response Surface ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
High Energy ◽  
Solid Loading ◽  
Control Group ◽  
Energy Yield ◽  
Tetraselmis Suecica ◽  
Antioxidant Power

Microalgae have been attracting attention as feedstock for biorefinery because they have various advantages, such as carbon fixation, high growth rate and high energy yield. The bioactive compounds and lutein contained in microalgae are known to be beneficial for human health, especially eye and brain health. In this study, in order to improve the recovery of bioactive extracts including lutein from Tetraselmis suecica with higher efficiency, an effective solvent was selected, and the extraction parameters such as temperature, time and solid loading were optimized by response surface methodology. The most effective solvent for lutein recovery was identified as 100% methanol, and the optimum condition was determined (42.4 °C, 4.0 h and 125 g/L biomass loading) by calculation of the multiple regression model. The maximum content of recovered lutein was found to be 2.79 mg/mL, and the ABTS radical scavenging activity (IC50) and ferric reducing antioxidant power (FRAP) value were about 3.36 mg/mL and 561.9 μmol/L, respectively. Finally, the maximum lutein recovery from T. suecica through statistical optimization was estimated to be 22.3 mg/g biomass, which was 3.1-fold improved compared to the control group.

scholarly journals Atorvastatin impairs liver mitochondrial function in obese Göttingen Minipigs but heart and skeletal muscle are not affected

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Liselotte Bruun Christiansen ◽  
Tine Lovsø Dohlmann ◽  
Trine Pagh Ludvigsen ◽  
Ewa Parfieniuk ◽  
Michal Ciborowski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Function ◽  
Citrate Synthase ◽  
Obese Group ◽  
Control Group ◽  
Dependent Manner ◽  
Respiratory Capacity ◽  
Protein Carbonyl Content ◽  
Functional Changes ◽  
Mitochondrial Respiratory

AbstractStatins lower the risk of cardiovascular events but have been associated with mitochondrial functional changes in a tissue-dependent manner. We investigated tissue-specific modifications of mitochondrial function in liver, heart and skeletal muscle mediated by chronic statin therapy in a Göttingen Minipig model. We hypothesized that statins enhance the mitochondrial function in heart but impair skeletal muscle and liver mitochondria. Mitochondrial respiratory capacities, citrate synthase activity, coenzyme Q10 concentrations and protein carbonyl content (PCC) were analyzed in samples of liver, heart and skeletal muscle from three groups of Göttingen Minipigs: a lean control group (CON, n = 6), an obese group (HFD, n = 7) and an obese group treated with atorvastatin for 28 weeks (HFD + ATO, n = 7). Atorvastatin concentrations were analyzed in each of the three tissues and in plasma from the Göttingen Minipigs. In treated minipigs, atorvastatin was detected in the liver and in plasma. A significant reduction in complex I + II-supported mitochondrial respiratory capacity was seen in liver of HFD + ATO compared to HFD (P = 0.022). Opposite directed but insignificant modifications of mitochondrial respiratory capacity were seen in heart versus skeletal muscle in HFD + ATO compared to the HFD group. In heart muscle, the HFD + ATO had significantly higher PCC compared to the HFD group (P = 0.0323). In the HFD group relative to CON, liver mitochondrial respiration decreased whereas in skeletal muscle, respiration increased but these changes were insignificant when normalizing for mitochondrial content. Oral atorvastatin treatment in Göttingen Minipigs is associated with a reduced mitochondrial respiratory capacity in the liver that may be linked to increased content of atorvastatin in this organ.

CMR fast-SENC segmental intramyocardial LV strain monitors decline in heart function before ejection fraction in patient with mitral valve disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Montenbruck ◽  
S Kelle ◽  
S Esch ◽  
A.K Schwarz ◽  
S Giusca ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Ejection Fraction ◽  
Cardiac Function ◽  
Mitral Valve Disease ◽  
Heart Function ◽  
Global Longitudinal Strain ◽  
Image Plane ◽  
Valve Disease ◽  
Peak Strain ◽  
Regional Dysfunction

Abstract Background Ejection fraction is the standard metric to analyze cardiac function in the left (LV) or right (RV) ventricles. However, these global metrics are not able to characterize patients in which the heart compensates for regional dysfunction. More sensitive metrics are needed to detect subclinical regional dysfunction before cardiac remodeling results in changes in ejection fraction (EF) and global longitudinal strain (GLS). Fast-SENC intramyocardial strain (fSENC) is a unique cardiac magnetic resonance imaging (CMR) modality that measures intramyocardial contraction in 1 heartbeat per image plane. This prospective registry compares segmental fSENC to standard CMR calculations (e.g. LVEF, volumes, mass, etc.) in patients with mitral valve disease. Methods A single center, prospective registry of CMR scans acquired with a 1.5T scanner were evaluated for standard CMR calculations as well as fSENC scans. Intramyocardial LV & RV strain was quantified with MyoStrain software. Three short axis scans (basal, midventricular, & apical) were used to calculate peak strain in 16 LV & 6 RV longitudinal segments while three long axis scans (2-, 3-, & 4-chamber) were used to calculate 21 LV & 5 RV circumferential segments. Results A total of 493 scans in 424 patients with moderate or severe mitral regurgitation were included in the study. Patients had an average (± stdev) age of 60 (15) yrs and BMI of 27 (4) kg/m2; 63% had arterial hypertension, 19% diabetes mellitus, 10% atrial fibrillation, 15% pulmonary disease, and 32% coronary artery disease. Figure 1 shows the non-linear relationship between segmental fSENC strain (% of normal LV segments ≤−17%) versus LVEF (R=0.81). Conclusion Segmental fSENC detects subclinical LV dysfunction before changes in LVEF. Evaluating segmental longitudinal and circumferential fSENC peak strain provides an alternative metric that shows consistent changes in cardiac function in patients with mitral valve disease irrespective of global calculations that are dependent on loading conditions. Funding Acknowledgement Type of funding source: None

Delivery of CD151 by Ultrasound Microbubbles in Rabbit Myocardial Infarction

Cardiology ◽  
2016 ◽  
Vol 135 (4) ◽  
pp. 221-227 ◽  
Author(s):  
Shao-Ling Yang ◽  
Ke-Qiang Tang ◽  
Jun-Jia Tao ◽  
Ai-Hong Wan ◽  
Yan-Duan Lin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Function ◽  
Rabbit Model ◽  
Physiological Saline ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Therapeutic Effects ◽  
Ventricular Ejection Fraction ◽  
Cluster Of Differentiation

Objectives: We aimed to evaluate whether ultrasound (US) and microbubble-mediated delivery of Cluster of Differentiation 151 (CD151) could enhance the therapeutic effects of CD151 on myocardial infarction (MI). Methods: A rabbit model of MI was established by a modified Fujita method. Then, 50 MI rabbits were randomly divided into 5 groups, including G1 (CD151 plasmid and physiological saline in the presence of US); G2 (CD151 and Sonovue in the presence of US); G3 (CD151 and Sonovue in the absence of US); G4 (Sonovue in the absence of US), and a control group (physiological saline in the absence of US). After 14 days of treatment, the expression of CD151 was detected by Western blot. Besides, vessel density of peri-infarcted myocardium was measured by immunohistochemistry, and cardiac function was analyzed by echocardiography. Results: The rabbit model of MI was established successfully. CD151 injection increased the expression of CD151 and microvessel density in the myocardium of MI rabbits. Heart function was significantly improved by CD151, which exhibited increased left ventricular ejection fraction, left ventricular fractional shortening and a reduced Tei index. Besides, US Sonovue significantly increased the expression efficiency of CD151. Conclusion: US microbubble was an effective vector for CD151 delivery. CD151 might be an effective therapeutic target for MI.

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