Engineered Membranes Improve Cardiac Function in Ischemic Rat Hearts

2010 ◽  
Author(s):  
Monica Sandri ◽  
Anna Tampieri ◽  
Joung H. Levialdi Ghiron ◽  
Gianluigi Condorelli
Keyword(s):  
Cardiac Function ◽  
Cardiac Tissue ◽  
Diglycidyl Ether ◽  
Beating Heart ◽  
Cardiac Cells ◽  
Neonatal Rat ◽  
Heart Cell ◽  
Collagen Membrane ◽  
Heart Cells ◽  
Type I

In the relatively young field of cardiac tissue engineering, different biomaterials, methods and techniques have been tested for cardiac repair. In this study we examined the validity of a series of new preformed membrane scaffolds, based on collagen type I, for the transplantation of cardiac cells. One type of membrane, cross-linked with 1,4-butanediol diglycidyl ether (BDDGE) and fibronectin-enriched, gave rise to spontaneously beating heart cell constructs 5–9 days after seeding with neonatal rat cardiac cells. This membrane was then grafted, with and without beating cardiac cells, onto the infarcted area of rat models of heart failure. Seriate echocardiography, performed on rats before transplantation and at 4 and 8 weeks after transplantation, showed that rats that received collagen membranes with beating cells showed an improvement in cardiac function after 8 weeks. These results suggest that this new type of collagen membrane can be used as vector for the transplantation of beating heart cells to the injured myocardium, hence representing an important potential tool for cardiac tissue repair technologies.

Confocal imaging of calcium in intact ventricular muscle provides a new view of excitation-contraction coupling

1996 ◽  
Vol 54 ◽  
pp. 738-739
Author(s):  
W.G. Wier
Keyword(s):  
Local Control ◽  
Cardiac Tissue ◽  
Cell Function ◽  
Isolated Heart ◽  
Cardiac Cells ◽  
Confocal Imaging ◽  
Ion Concentration ◽  
Heart Cell ◽  
Free Calcium ◽  
Heart Cells

A fundamentally new understanding of cardiac excitation-contraction (E-C) coupling is being developed from recent experimental work using confocal microscopy of single isolated heart cells. In particular, the transient change in intracellular free calcium ion concentration ([Ca2+]i transient) that activates muscle contraction is now viewed as resulting from the spatial and temporal summation of small (∼ 8 μm3), subcellular, stereotyped ‘local [Ca2+]i-transients' or, as they have been called, ‘calcium sparks'. This new understanding may be called ‘local control of E-C coupling'. The relevance to normal heart cell function of ‘local control, theory and the recent confocal data on spontaneous Ca2+ ‘sparks', and on electrically evoked local [Ca2+]i-transients has been unknown however, because the previous studies were all conducted on slack, internally perfused, single, enzymatically dissociated cardiac cells, at room temperature, usually with Cs+ replacing K+, and often in the presence of Ca2-channel blockers. The present work was undertaken to establish whether or not the concepts derived from these studies are in fact relevant to normal cardiac tissue under physiological conditions, by attempting to record local [Ca2+]i-transients, sparks (and Ca2+ waves) in intact, multi-cellular cardiac tissue.

scholarly journals Photoinduced removal of nifedipine reveals mechanisms of calcium antagonist action on single heart cells.

1985 ◽  
Vol 86 (3) ◽  
pp. 353-379 ◽  
Author(s):  
A M Gurney ◽  
J M Nerbonne ◽  
H A Lester
Keyword(s):  
Calcium Channels ◽  
Dissociation Constants ◽  
Light Flash ◽  
Cardiac Cells ◽  
Current Amplitude ◽  
Neonatal Rat ◽  
Resting Potential ◽  
Open Channels ◽  
Heart Cell ◽  
Heart Cells

The currents through voltage-activated calcium channels in heart cell membranes are suppressed by dihydropyridine calcium antagonists such as nifedipine. Nifedipine is photolabile, and the reduction of current amplitude by this drug can be reversed within a few milliseconds after a 1-ms light flash. The blockade by nifedipine and its removal by flashes were studied in isolated myocytes from neonatal rat heart using the whole-cell clamp method. The results suggest that nifedipine interacts with closed, open, and inactivated calcium channels. It is likely that at the normal resting potential of cardiac cells, the suppression of current amplitude arises because nifedipine binds to and stabilizes channels in the resting, closed state. Inhibition is enhanced at depolarized membrane potentials, where interaction with inactivated channels may also become important. Additional block of open channels is suggested when currents are carried by Ba2+ but is not indicated with Ca2+ currents. Numerical simulations reproduce the experimental observations with molecular dissociation constants on the order of 10(-7) M for closed and open channels and 10(-8) M for inactivated channels.

Abstract 1855: Transmural Myocardial Repair with Engineered Heart Tissue Grafts

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Daniel Biermann ◽  
Michael Didié ◽  
Bijoy Chandapillai Karikkineth ◽  
Claudia Lange ◽  
Thomas Eschenhagen ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Heart Tissue ◽  
Laser Scanning Microscopy ◽  
Neonatal Rat ◽  
Heart Weight ◽  
Heart Cells ◽  
Type I ◽  
Myocardial Repair ◽  
Engineered Heart Tissue ◽  
Tissue Grafts

Engineered Heart Tissue (EHT) can be utilized to partially repair infarcted myocardium in rats. Here, we investigated the feasibility of EHT-grafts as transmural wall replacement in a heterotopic transplantation model. Methods: EHTs (diameter: 15 mm, thickness: 1– 4 mm) were generated from 12.5 ×10 6 neonatal rat heart cells, collagen type I, and matrigel. Similarly, non-contractile constructs were generated from rat cardiac fibroblasts (FB) and mesenchymal stem cells (MSC). Grafts were surgically inserted into large transmural defects (diameter: 6 mm) in the left ventricle of explanted donor hearts. Subsequently, “treated” hearts were transplanted into weight-matched (308±12 g; n=14), immune suppressed (cyclosporine, azathioprine, prednisolone) Wistar rats in heterotopic position. All transmural defects were also covered with an aortic patch to prevent bleeding from the ventricles. Sham surgeries included aortic patch implantations only. Heterotopic hearts were harvested after 28 days and subjected to morphological analyses by confocal laser scanning microscopy (CLSM). Results: Heart transplant weight at the time of implantation was 1.1±0.02 g (n=14). Heterotopic heart weight increased substantially in Sham (2.4±0.3 g, n=3) and FB-graft (2.1±0.1 g, n=3) animals, whereas MSC- (1.7±0.2 g, n=4) and EHT-graft (1.3±0.1 g, n=4; p<0.05 vs. Sham) animals showed a smaller or no increase in weight, respectively. EHT grafts remained contractile throughout the observation period. CLSM revealed that EHT-grafts established oriented muscle bundles (actin and actinin staining) inside the transmural defects and were strongly vascularized (CD31 and smooth muscle actin staining; lectin labeling) leading to partial reconstitution of the myocardial continuity. This was not observed in animals with FB- and MSC-grafts. However, MSC-grafts, but not FB-grafts, contained newly formed vessels with a markedly larger diameter than observed in EHT-grafts (21±6 vs. 5±0.7 μm; p<0.05). Conclusion: EHTs can be utilized as myocardial tissue grafts to reconstruct and prevent pathological enlargement of the left ventricle. This study constitutes a first step to establish a novel transmural myocardial repair technology involving fully bioengineered heart muscle.

Cultivation of beating heart cells from frozen heart cell suspensions

1967 ◽  
Vol 54 (7) ◽  
pp. 174-174 ◽  
Author(s):  
A. Wollenberger ◽  
W. Halle ◽  
Eva Kallabis ◽  
B. Kleitke ◽  
U. Hinterberger ◽  
...  
Keyword(s):  
Beating Heart ◽  
Cell Suspensions ◽  
Heart Cell ◽  
Heart Cells

scholarly journals Effect of Quercetin and Intermittent and Continuous Exercise on Catalase, Superoxide dismutase, and Malondialdehyde in the Heart of Rats with Colon Cancer

2021 ◽  
Author(s):  
Behrooz Talaei ◽  
Mohammad Panji ◽  
Fatemeh Nazari Robati ◽  
Sajjad Tezerji
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Superoxide Dismutase ◽  
Cardiac Tissue ◽  
Intermittent Exercise ◽  
Heart Tissue ◽  
Cardiac Cells ◽  
Heart Cells ◽  
Oxidative Stress Biomarkers ◽  
Continuous Exercise

Background: Colorectal cancer is the fourth leading cause of death globally, and the second most common cancer in Europe. About 8% of all cancer-related deaths occur due to colorectal cancer, and the highest prevalence has been reported in Asia and Eastern Europe. Methods: In this experimental study, 80 rats were divided into two groups of cases (n=70) and controls (n=10). Colorectal cancer was induced weekly in rats by subcutaneous injection of 15 mg/kg Azoxymethane. The rats were then divided into 7 experimental subgroups of patients, saline, quercetin, intermittent exercise, continuous exercise, quercetin plus intermittent, and quercetin plus continuous exercise. Oxidative stress biomarkers, including superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were measured in the rats’ heart tissue by the ELISA method. Data were analyzed using ANOVA by SPSS software. Results: Oxidative stress in heart cells increased due to colorectal cancer. Quercetin alone or in combination with exercise significantly increased mean levels of CAT and SOD in the heart tissue of rats compared with patient and saline groups (P<0.0001). In contrast, the MDA level was significantly decreased (P<0.05). Conclusion: Colorectal cancer increased the oxidative stress in cardiac cells. Quercetin alone improved oxidative stress in cardiac tissue, and its combination with exercise was more effective.

scholarly journals Activin Signaling Regulates Autophagy and Cardiac Aging through mTORC2

2017 ◽  
Author(s):  
Kai Chang ◽  
Ping Kang ◽  
Ying Liu ◽  
Kerui Huang ◽  
Erika Taylor ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Cardiac Tissue ◽  
Type I ◽  
Specific Expression ◽  
Cardiac Aging ◽  
Activin Signaling ◽  
Cardiac Health ◽  
Age Related ◽  
Heart Performance ◽  
Slow Heart Rate

AbstractAge-dependent loss of cardiac tissue homeostasis largely impacts heart performance and contributes significantly to cardiovascular diseases later in life. Cellular quality control machinery, such as autophagy/lysosome system, plays a crucial role in maintaining cardiac health and preventing age-induced cardiomyopathy and heart failure. However, how aging alters the autophagy/lysosome system to impact cardiac function remains largely unknown. Here using Drosophila heart as a model system, we show that activin signaling, a member of TGF-beta superfamily, negatively regulates cardiac autophagy and cardiac health during aging. We found that cardiac-specific knockdown of Daw, an activin-like protein in Drosophila, increased cardiac autophagy and prevented age-related cardiac dysfunction, including arrhythmia and bradycardia (slow heart rate). Inhibition of autophagy blocked Daw knockdown-mediated cardioprotection. Consistently, cardiac-specific expression of constitutively activated activin type I receptor Babo disrupted cardiac function at young ages. Intriguingly, the key autophagy regulator, mechanistic target of rapamycin complex 1 (mTORC1), was not involved in activin-mediated autophagy. Instead, activin signaling genetically interacted with Rictor, the key subunit of mTORC2, to regulate autophagy and cardiac aging. Knockdown of Daw increased the mRNA expression of Rictor and the phosphorylation of AKT in fly hearts. Finally, cardiac-specific silencing of Daw not only improved cardiac health, but also prolonged lifespan. Thus, our findings highlight an emerging role of activin signaling and mTORC2 in the regulation of autophagy and cardiac aging.

A superfusion system to study border zones in confluent cultures of neonatal rat heart cells

1998 ◽  
Vol 274 (6) ◽  
pp. H2001-H2008 ◽  
Author(s):  
Christopher J. Hyatt ◽  
John J. Lemasters ◽  
Barbara J. Muller-Borer ◽  
Timothy A. Johnson ◽  
Wayne E. Cascio
Keyword(s):  
Cardiac Tissue ◽  
Fluorescent Microscopy ◽  
Cell Monolayer ◽  
Neonatal Rat ◽  
Border Zone ◽  
Heart Cells ◽  
Fluid Viscosity ◽  
Ion Regulation ◽  
Border Zones ◽  
Superfusion System

We present a new experimental method to study intracellular ion regulation in cultured cardiomyocytes at a border zone separating two different and distinct environments. Our system uses a dual-flow superfusion chamber to produce two different but adjacent environments over a monolayer of cardiomyocytes. Fluorescent microscopy of fluorescein showed that the transition between the two environments was nearly linear and was 220–320 μm wide depending on fluid viscosity and velocity. We superfused cultured monolayers on one side with a solution at pH 6.5 and on the other side with a solution at pH 7.4. We observed a sharply demarcated difference in intracellular pH (pHi) between the two halves of the cell monolayer as measured with the fluorescent pHi indicator carboxy-seminaphthorhodafluor-1. The demarcation of pHi corresponded well with the demarcation of the border measured with fluorescein. We conclude that our superfusion system will facilitate the study of intercellular communication and interactions across boundaries of cardiac tissue where different ionic or metabolic conditions are present, for example, between ischemic and nonischemic myocardium.

Uncoupling of cardiac cells by fatty acids: structure-activity relationships

1991 ◽  
Vol 260 (3) ◽  
pp. C439-C448 ◽  
Author(s):  
J. M. Burt ◽  
K. D. Massey ◽  
B. N. Minnich
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Decanoic Acid ◽  
Cardiac Cells ◽  
Neonatal Rat ◽  
Heart Cells ◽  
Dependent Manner ◽  
Rat Heart Cells

The permeability and conductance of gap junctions between pairs of neonatal rat heart cells were rapidly and reversibly decreased by oleic acid in a dose- and time-dependent manner. Other unsaturated fatty acids (C-18: cis 6, 9, or 11, and C-18, 16, and 14, cis 9), saturated fatty acids (C-10, 12, and 14), and saturated fatty alcohols (C-8, 10, and 12) also caused uncoupling. The most effective compounds of the unsaturated and saturated fatty acid and saturated fatty alcohol series caused essentially complete uncoupling at comparable aqueous concentrations. However, oleic acid uncoupled cells at membrane concentrations as low as 1 mol%, whereas decanoic acid required upwards of 35 mol%. The channels that support the action potential remained functional at these same membrane concentrations. The data are discussed in terms of the possible mechanism by which these compounds cause uncoupling and the possible role of uncoupling by nonesterified free fatty acids in the initiation of arrhythmias during and after ischemic insults.

scholarly journals Adenosine formation and release from neonatal-rat heart cells in culture

1985 ◽  
Vol 229 (3) ◽  
pp. 799-805 ◽  
Author(s):  
P Meghji ◽  
C A Holmquist ◽  
A C Newby
Keyword(s):  
Rat Heart ◽  
Neonatal Rat ◽  
Heart Cell ◽  
Heart Cells ◽  
Dependent Manner ◽  
Nucleoside Transporter ◽  
Concentration Dependent Manner ◽  
Cells In Culture ◽  
Neonatal Rat Heart ◽  
Rat Heart Cells

The incorporation of [3H]adenosine (10 microM) into neonatal-rat heart cell nucleotides was inhibited in a concentration-dependent manner, such that 50% inhibition was obtained with 0.75 microM-dipyridamole, 0.26 microM-hexobendine or 0.22 microM-dilazep. Adenosine formation was accelerated 2.5-fold to 2.1 +/- 0.3 nmol/10(7) cells in 10 min when cells were incubated with a combination of 30 mM-2-deoxyglucose and 2 micrograms of oligomycin/ml. Of the newly formed adenosine, 6 +/- 2% was in the cells. Dipyridamole, hexobendine or dilazep (10 microM) increased the amount of adenosine in the cells and decreased that in the medium such that 45-50% of the newly formed adenosine was in the cells. Antibodies which inhibited ecto-5'-nucleotidase by 98.7 +/- 0.3% did not alter the rate of adenosine formation or its distribution between cells and medium. We conclude that adenosine was formed in the cytoplasm during catabolism of cellular ATP and was released via the dipyridamole-sensitive symmetric nucleoside transporter.

Abstract 262: Depolarization Stimulates Neonatal Cardiomyocyte Proliferation In Vitro

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Corin Williams ◽  
Michael Levin ◽  
Lauren D Black
Keyword(s):  
Cardiac Tissue ◽  
Heart Defects ◽  
Cell Types ◽  
Cardiac Cells ◽  
Neonatal Rat ◽  
Resting Membrane Potential ◽  
Cardiomyocyte Proliferation ◽  
Potassium Gluconate ◽  
Hypertrophic Growth

Cardiac tissue engineering is a promising approach for treating children with congenital heart defects. However, as cardiomyocytes (CMs) undergo a rapid transition from hyperplastic to hypertrophic growth after birth, a major challenge to the development of engineered cardiac tissue is the limited proliferation of CMs. Mature CMs and other terminally differentiated cell types tend to have a highly negative resting membrane potential (Vmem) while stem cells and less mature cells tend to have Vmem closer to zero. Vmem has been shown to play an important role in cell differentiation and proliferation. We hypothesized that depolarization of cardiac cells would stimulate CM proliferation in vitro . To test our hypothesis, we isolated neonatal rat cardiac cells and cultured them for 24 hr under standard conditions. Cells were then subjected to depolarization treatment for 72 hr using potassium gluconate or ouabain at various concentrations. Samples were fixed and stained for cardiac α-actin (Fig 1A, red) and phospho-histone H3 (Fig 1A, green) to assess CM mitosis. We found that potassium gluconate had no significant effect while ouabain significantly increased CM mitosis, suggesting Vmem regulation via Na/K-ATPase. CM-specific proliferation was significantly higher with 10nM (p= 0.015) and 100nM (p=0.008) ouabain treatment compared to controls (n=3) (Fig 1B). Cell density was significantly higher with 100μM ouabain versus controls (2656 ± 50 vs. 2026 ± 117 cells/mm 2 ), indicating increased cardiac cell proliferation (Fig 1C). Our findings suggest that depolarization promotes CM proliferation and may be a novel approach to encourage growth of engineered cardiac tissue in vitro .

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