Silencing of NHE-1 blunts the slow force response to myocardial stretch

2011 ◽  
Vol 111 (3) ◽  
pp. 874-880 ◽  
Author(s):  
Néstor G. Pérez ◽  
Mariela B. Nolly ◽  
Mirian C. Roldan ◽  
María C. Villa-Abrille ◽  
Eugenio Cingolani ◽  
...  
Keyword(s):  
Lentiviral Vector ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Force Response ◽  
Rapid Phase ◽  
Key Factor ◽  
Myocardial Stretch ◽  
And Function

Myocardial stretch induces a biphasic force response: a first abrupt increase followed by a slow force response (SFR), believed to be the in vitro manifestation of the Anrep effect. The SFR is due to an increase in Ca2+ transient of unclear mechanism. We proposed that Na+/H+ exchanger (NHE-1) activation is a key factor in determining the contractile response, but recent reports challenged our findings. We aimed to specifically test the role of the NHE-1 in the SFR. To this purpose small hairpin interference RNA capable of mediating specific NHE-1 knockdown was incorporated into a lentiviral vector (l-shNHE1) and injected into the left ventricular wall of Wistar rats. Injection of a lentiviral vector expressing a nonsilencing sequence (scramble) served as control. Myocardial NHE-1 protein expression and function (the latter evaluated by the recovery of pHi after an acidic load and the SFR) were evaluated. Animals transduced with l-shNHE1 showed reduced NHE-1 expression (45 ± 8% of controls; P < 0.05), and the presence of the lentivirus in the left ventricular myocardium, far from the site of injection, was evidenced by confocal microscopy. These findings correlated with depressed basal pHi recovery after acidosis [maxdpHi/d t 0.055 ± 0.008 (scramble) vs. 0.009 ± 0.004 (l-shNHE1) pH units/min, P < 0.05], leftward shift of the relationship between JH+ (H+ efflux corrected by the intrinsic buffer capacity), and abolishment of SFR (124 ± 2 vs. 101 ± 2% of rapid phase; P < 0.05) despite preserved ERK1/2 phosphorylation [247 ± 12 (stretch) and 263 ± 23 (stretch l-shNHE1) % of control; P < 0.05 vs. nonstretched control], well-known NHE-1 activators. Our results provide strong evidence to propose NHE-1 activation as key factor in determining the SFR to stretch.

β-blockade abolishes the augmented cardiac tPA release induced by transactivation of heterodimerised bradykinin receptor-2 and β2-adrenergic receptor in vivo

2014 ◽  
Vol 112 (11) ◽  
pp. 951-959 ◽  
Author(s):  
Morten Eriksen ◽  
Arnfinn Ilebekk ◽  
Alessandro Cataliotti ◽  
Cathrine Rein Carlson ◽  
Torstein Lyberg ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Sympathetic Nerves ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Adrenergic Stimulation ◽  
Β2 Adrenergic Receptor ◽  
Β Blocker

SummaryBradykinin (BK) receptor-2 (B2R) and β2-adrenergic receptor (β2AR) have been shown to form heterodimers in vitro. However, in vivo proofs of the functional effects of B2R-β2AR heterodimerisation are missing. Both BK and adrenergic stimulation are known inducers of tPA release. Our goal was to demonstrate the existence of B2R-β2AR heterodimerisation in myocardium and to define its functional effect on cardiac release of tPA in vivo. We further investigated the effects of a non-selective β-blocker on this receptor interplay. To investigate functional effects of B2R-β2AR heterodimerisation (i. e. BK transactivation of β2AR) in vivo, we induced serial electrical stimulation of cardiac sympathetic nerves (SS) in normal pigs that underwent concomitant BK infusion. Both SS and BK alone induced increases in cardiac tPA release. Importantly, despite B2R desensitisation, simultaneous BK infusion and SS (BK+SS) was characterised by 2.3 ± 0.3-fold enhanced tPA release compared to SS alone. When β-blockade (propranolol) was introduced prior to BK+SS, tPA release was inhibited. A persistent B2R-β2AR heterodimer was confirmed in BK-stimulated and nonstimulated left ventricular myocardium by immunoprecipitation studies and under non-reducing gel conditions. All together, these results strongly suggest BK transactivation of β2AR leading to enhanced β2AR-mediated release of tPA. Importantly, non-selective β-blockade inhibits both SS-induced release of tPA and the functional effects of B2R-β2AR heterodimerisation in vivo, which may have important clinical implications.

Cardiac microdialysis in isolated rat hearts: interstitial purine metabolites during ischemia

1992 ◽  
Vol 262 (6) ◽  
pp. H1934-H1938 ◽  
Author(s):  
D. G. Van Wylen ◽  
T. J. Schmit ◽  
R. D. Lasley ◽  
R. L. Gingell ◽  
R. M. Mentzer
Keyword(s):  
Uric Acid ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Isolated Perfused Heart ◽  
Perfused Heart ◽  
Purine Metabolites ◽  
Valuable Adjunct ◽  
Rat Hearts

Cardiac microdialysis is a recently developed technique that allows intramyocardial interstitial fluid (ISF) to be sampled via the implantation and perfusion of a small, hollow dialysis fiber within the myocardium. The purpose of this paper is to describe initial studies using cardiac microdialysis in the isolated perfused heart. Microdialysis probes, constructed in the laboratory, were implanted in the left ventricular myocardium of isolated perfused rat hearts and perfused at 0.5 microliter/min with Krebs-Henseleit buffer. The effluent dialysate, assayed for adenosine, inosine, hypoxanthine, xanthine, and uric acid, was used as an index of intramyocardial levels of these purine metabolites. All metabolites were elevated initially after implantation, declined rapidly in the first 45 min, and were then stable for the next 90 min. Based on in vitro percent recovery data, baseline dialysate concentrations were extrapolated to yield estimates of intramyocardial ISF (in microM) 0.47 adenosine, 0.85 inosine, 0.29 hypoxanthine, 0.49 xanthine, and 8.6 uric acid. During global zero-flow ischemia (37 degrees C), dialysate levels of all purine metabolites were elevated, with inosine being the predominant compound. Pretreatment of the hearts with 50 microM erythro-9-(2-hydroxy-3-nonyl)adenine, an adenosine deaminase inhibitor, markedly enhanced ISF adenosine accumulation and attenuated the accumulation of inosine, hypoxanthine, and xanthine. The simplicity and versatility of cardiac microdialysis in the isolated perfused heart suggest that this technique may be a valuable adjunct to the many studies performed using this preparation.

scholarly journals DIAGNOSTIC OF THE ATHLETE’S HEART AND FACTORS AFFECTING ITS DEVELOPING

2021 ◽  
Vol 74 (5) ◽  
pp. 1158-1163
Author(s):  
Serhiy V. Popov ◽  
Oleksandr I. Smiyan ◽  
Andrii M. Loboda ◽  
Viktoriia O. Petrashenko ◽  
Olena K. Redko ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Heart Development ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Athlete’S Heart ◽  
Left Ventricular Myocardium ◽  
Factors Affecting ◽  
Ultrasound Study ◽  
And Function ◽  
Athlete's Heart

The aim: Studying the features of the structure and function of the heart in athletes and identifying the factors that influence the development of these changes. Materials and methods: The study included 54 athletes, 29 men and 25 women. The ultrasound study was performed according to standard methods with determining the size of the main structures of the heart, indicators normalized to body surface area, height. Results: The heart of dilatation and hypertrophy of the left ventricular myocardium were found in 25.93% of the athletes. When comparing the diameter of the left ventricle of individual athletes with the average values of the norm, their excess was found in 94.44% of athletes. The Odds ratio (OR) of the relationship between left ventricle diameter (LVd) and time of the exercise less than 10 y was 16.13, time of the exercise less than 5 y – 0.17 (p <0.05). OR of increase LVd to age less than 20 years was 3.56 units (p <0.05). The ejection fraction was above the normative mean in 75.93%, as well as the ratio of the periods of filling of the ventricles. Conclusions: The most common sign of an athlete’s heart development was left ventricular dilatation, which occurred at a rate of 25 percent. Age less than 20 years and the duration of sports activities from 5 to 10 years is associated with a higher frequency of the athlete’s heart.

scholarly journals Value of Contrast-Enhanced Echocardiography of Left Cardiac Chambers for Clinical Practice

Kardiologiia ◽  
2018 ◽  
Vol 58 (11) ◽  
pp. 53-62
Author(s):  
M. N. Alekhin
Keyword(s):  
Clinical Practice ◽  
Side Effects ◽  
Myocardial Ischemia ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Structure And Function ◽  
Left Ventricular Myocardium ◽  
Contrast Enhanced ◽  
Contrast Enhanced Echocardiography ◽  
And Function

This literature review in devoted to the potential of application of contrast-enhanced echocardiography (CEE) for assessment of structure and function of left cardiac chambers. It contains based on current recommendations discussion of main indications for CEE and analysis of its possibilities in evaluation of perfusion of the left ventricular myocardium, detection of myocardial ischemia, and assessment of myocardial viability. Data on CEE safety and possible side effects associated with the use of ultrasound contrasts are also presented.

Effect of postburn serum on in vitro respiration of normal myocardium

1963 ◽  
Vol 18 (4) ◽  
pp. 821-823 ◽  
Author(s):  
Arthur A. Spector
Keyword(s):  
Fatty Acids ◽  
Oxygen Consumption ◽  
Technical Assistance ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Burn Shock ◽  
Cardiac Defect ◽  
Electrophoretic Patterns

An in vitro respiratory system using normal guinea pig left ventricular myocardium is described. QO2 values are given for this preparation incubated with representative substrates. A larger elevation in oxygen consumption is seen with linoleic acid as compared to other unesterified fatty acids tested. Serum obtained from dogs before and 15 min after flash burn was incubated with this heart slice system. No differences in oxygen uptake are noted between addition of control and postburn serum. No major serum enzymatic or chemical alterations are found at 15 min postburn. Plasma protein electrophoretic patterns remain unchanged at 15 and 40 min after injury. These results do not support the concept that the cardiac defect in early burn shock is caused by a circulating substance that either inhibits oxidation or uncouples oxidative phosphorylation by the myocardium. Note: (With the Technical Assistance of Ralph A. Abreo and Raburn Jackson) Submitted on November 15, 1962

scholarly journals Effects of Telmisartan on Myocardial Protein Profiles in Hypertensive Rats

2021 ◽  
Vol 34 (3) ◽  
pp. 299-299
Author(s):  
Yu Feng ◽  
Man-li Zhou ◽  
Jian-zhang Wang ◽  
Jia-qi Zhang ◽  
Shu-le Qian ◽  
...  
Keyword(s):  
Heat Shock ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Sterile Water ◽  
Protein Profiles ◽  
Related Protein ◽  
Hypertensive Rats ◽  
Treatment Groups ◽  
Proteasome 26S

Abstract Background To investigate the effects of telmisartan on the protein profiles of the left ventricular myocardium in spontaneously hypertensive rats (SHR). Methods Sixteen SHR were randomly divided into control and telmisartan treatment groups. Rats were treated with sterile water (10 ml/kg) or telmisartan (4.33 mg/kg) by gavage for 12 weeks. Wistar-Kyoto (WKY) rats treated with sterile water (10 ml/kg) as controls. At the end of 12 weeks of control or telmisartan treatment, rats were sacrificed, and hearts were collected for protein preparations, isotope labeling, and mass spectrometric analysis. Results In total, there were 23 differentially expressed proteins in the left ventricular myocardium between control and telmisartan treatment groups in SHR. Compared with the telmisartan group, the upregulated proteins in the SHR were dual-specificity mitogen-activated protein kinase kinase 3-like, transgelin, and haptoglobin subtype 2. The downregulated proteins in the SHR were as follows: von Willebrand factor (fragment), kininogen 1, small ribonucleoprotein-related protein, fibrinogen beta chain, protein mass 3 (fragment), proteasome 26s, heat shock protein 27-related protein 1, tenascin X, fibronectin subtype 2, transferrin receptor protein, platelets 1, cathepsin L1, complement factor B, isoform CRA_b, fibrinogen isomer, immunoglobulin heavy chain (γ polypeptide), and α 1 antiprotease. Conclusions Telmisartan differentially regulates myocardial protein expression in hypertensive rats including heat shock protein 27, fibrinogen, fibronectin, proteasome 26s and transgelin, as well as proteins in biochemical, metabolic, and signal transduction pathways. These changes in protein expression may contribute to the antihypertrophic effects of telmisartan in hypertension.

scholarly journals Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yankun Lyu ◽  
Vipin K. Verma ◽  
Younjee Lee ◽  
Iosif Taleb ◽  
Rachit Badolia ◽  
...  
Keyword(s):  
Heart Function ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Excitation Contraction Coupling ◽  
Transverse Tubular System ◽  
Contraction Coupling ◽  
Senescent Phenotype ◽  
Cellular Microstructure ◽  
T System

AbstractIt is well established that the aging heart progressively remodels towards a senescent phenotype, but alterations of cellular microstructure and their differences to chronic heart failure (HF) associated remodeling remain ill-defined. Here, we show that the transverse tubular system (t-system) and proteins underlying excitation-contraction coupling in cardiomyocytes are characteristically remodeled with age. We shed light on mechanisms of this remodeling and identified similarities and differences to chronic HF. Using left ventricular myocardium from donors and HF patients with ages between 19 and 75 years, we established a library of 3D reconstructions of the t-system as well as ryanodine receptor (RyR) and junctophilin 2 (JPH2) clusters. Aging was characterized by t-system alterations and sarcolemmal dissociation of RyR clusters. This remodeling was less pronounced than in HF and accompanied by major alterations of JPH2 arrangement. Our study indicates that targeting sarcolemmal association of JPH2 might ameliorate age-associated deficiencies of heart function.

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