scholarly journals Expression of FAS adjacent to fibrotic foci in the failing human heart is not associated with increased apoptosis

1999 ◽  
Vol 277 (2) ◽  
pp. H445-H451 ◽  
Author(s):  
Gerasimos Filippatos ◽  
Carlos Leche ◽  
Ruben Sunga ◽  
Anthony Tsoukas ◽  
Prodromos Anthopoulos ◽  
...  
Keyword(s):  
Human Heart ◽  
Chromatin Condensation ◽  
Artery Bypass ◽  
Spatial Relationship ◽  
Left Ventricular ◽  
Diffuse Fibrosis ◽  
Heart Cell ◽  
Heart Cells ◽  
Reduced Ejection Fraction ◽  
Failing Heart

Fibrosis in the heart may result from loss of myocytes, which are replaced by collagens. Apoptosis is now known to contribute to myocyte loss in the failing human heart. The mechanisms underlying the induction of cardiomyocyte apoptosis, and thus the expansion of fibrotic foci in the failing heart, are poorly understood. We hypothesized that viable heart cells adjacent to fibrotic foci might become “predisposed” to apoptosis by expression of the receptor FAS (APO1, CD95). We therefore studied the spatial relationship of FAS expression and fibrosis in patients with heart failure. Left ventricular biopsies were obtained from seven patients undergoing coronary artery bypass grafting. All patients had reduced ejection fraction but varied in New York Heart Association class score at the time of surgery. Heart cell apoptosis, fibrosis, and FAS expression were studied by propidium iodide and in situ end labeling (ISEL) of DNA, Picrosirius red staining, and immunohistochemistry. All patient samples exhibited, albeit to varying degrees, apoptosis detected by ISEL, chromatin condensation, and nuclear fragmentation. In all samples, fibrosis (collagen) was evident both perivascular and in isolated regions of scarring. Regardless of the extent of fibrosis or detectable apoptosis, FAS expression was observed in regions immediately adjacent to the fibrosis, but not in regions distal to fibrosis, nor in fibrotic areas devoid of nuclei. Expression of FAS was found adjacent to both perivascular and diffuse fibrosis, and ISEL-positive nuclei were found within cells reacting positively with anti-FAS antibodies. However, ISEL-positive nuclei were no more abundant in FAS-positive regions (67.6 ± 5.8% of total nuclei) than in FAS-negative areas (69.5 ± 9.8%). We conclude that expression of FAS occurs in remaining heart cells adjacent to fibrosis of either perivascular or presumed reparative origin. Although this phenomenon could contribute to the expansion of fibrotic foci, FAS-induced apoptosis in the failing heart may not be more prevalent than apoptosis initiated by other signaling mechanisms.

Transcription, storage and release of atrial natriuretic factor in the failing human heart

1991 ◽  
Vol 80 (4) ◽  
pp. 285-291 ◽  
Author(s):  
Thomas A. Fischer ◽  
Markus Haass ◽  
Rainer Dietz ◽  
Roland C. Willenbrock ◽  
Werner Saggau ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Atrial Natriuretic Factor ◽  
Human Heart ◽  
Artery Bypass ◽  
Plasma Concentrations ◽  
Left Ventricular ◽  
Right Atrial ◽  
Heart Catheterization ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

1. In this study the relationship between the synthesis of atrial natriuretic factor at the level of atrial natriuretic factor mRNA and the atrial storage and circulating plasma levels of atrial natriuretic factor were investigated in 15 patients with heart failure. The patients underwent right and left heart catheterization before cardiac surgery for valve replacement or coronary artery bypass grafting. 2. Plasma concentrations of atrial natriuretic factor were correlated to atrial levels of atrial natriuretic factor mRNA. Atrial levels of atrial natriuretic factor mRNA and plasma concentrations of atrial natriuretic factor exhibited a close correlation to both pulmonary artery pressure and left atrial pressure. No relationship, however, could be found between the right atrial content of atrial natriuretic factor and both the expression of atrial natriuretic factor mRNA in the atria and the plasma levels of atrial natriuretic factor. 3. From these data it may be concluded that increased plasma levels of atrial natriuretic factor in the pressure-and/or volume-overloaded heart are associated with an elevated level of atrial natriuretic factor mRNA. We suggest that not only plasma levels of atrial natriuretic factor but also the expression of atrial natriuretic factor in the atria are related to left ventricular filling pressures in the failing human heart.

scholarly journals Haemodynamics Support during Surgical Myocardial Revascularisation in Patients with Systolic Left Ventricular Dysfunction

2021 ◽  
Vol 11 (3) ◽  
pp. 228-234
Author(s):  
N. V. Kharitonov ◽  
V. V. Vitsukaev ◽  
N. A. Trofimov ◽  
P. D. Makalsky ◽  
V. N. Zavgorodny
Keyword(s):  
Ejection Fraction ◽  
Extracorporeal Circulation ◽  
Heart Surgery ◽  
Artery Bypass ◽  
Coronary Bypass ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Treatment Standard

Coronary heart disease remains a leading cause of death worldwide, and coronary bypass surgery -- the treatment standard in haemodynamically significant multivessel and/or trunk coronary stenosis. Intraoperative haemodynamics support during coronary artery bypass grafting (CABG) in patients with reduced ejection fraction currently remains controversial. Manifold evidence favours CABG with no extracorporeal circulation in higher risk patients to avoid the system’s frequent complications of blood transfusion, renal failure, bleeding, wound infection, cerebrovascular events and humoral disturbances. On the other hand, CABG with extracorporeal circulation and heart arrest allows a bloodless operating field and complete revascularisation in most, often very complex, cases. The complication rate and outcome in beating-heart surgery are reckoned to depend directly on the relevant surgeon’s and clinic experience, which makes many relinquish the technique due to a limited history of skill. This essay overviews the current state of the art, discussions of recent systematic studies on intraoperative haemodynamics support in patients with reduced left ventricular ejection fraction and touches upon the importance of surgeon’s experience for the operation outcome.

l-Arginine protects human heart cells from low-volume anoxia and reoxygenation

2002 ◽  
Vol 282 (3) ◽  
pp. H805-H815 ◽  
Author(s):  
Noritsugu Shiono ◽  
Vivek Rao ◽  
Richard D. Weisel ◽  
Muneyasu Kawasaki ◽  
Ren-Ke Li ◽  
...  
Keyword(s):  
Guanylate Cyclase ◽  
Human Heart ◽  
Cell Model ◽  
Heart Cell ◽  
Heart Cells ◽  
No Production ◽  
Cellular Injury ◽  
Protective Effects ◽  
No Donor ◽  
Low Volume

Protective effects ofl-arginine were evaluated in a human ventricular heart cell model of low-volume anoxia and reoxygenation independent of alternate cell types. Cell cultures were subjected to 90 min of low-volume anoxia and 30 min of reoxygenation. l-Arginine (0–5.0 mM) was administered during the preanoxic period or the reoxygenation phase. Nitric oxide (NO) production, NO synthase (NOS) activity, cGMP levels, and cellular injury were assessed. To evaluate the effects of thel-arginine on cell signaling, the effects of the NOS antagonist N G-nitro-l-arginine methyl ester, NO donor S-nitroso- N-acetyl-penicillamine, guanylate cyclase inhibitor methylene blue, cGMP analog 8-bromo-cGMP, and ATP-sensitive K+ channel antagonist glibenclamide were examined. Our data indicate that low-volume anoxia and reoxygenation increased NOS activity and facilitated the conversion ofl-arginine to NO, which provided protection against cellular injury in a dose-dependent fashion. In addition,l-arginine cardioprotection was achieved by the activation of guanylate cyclase, leading to increased cGMP levels in human heart cells. This action involves a glibenclamide-sensitive, NO-cGMP-dependent pathway.

Diagnosis and Management of Ischemic Mitral Regurgitation: Evidence-Based Clinical Decision Making at the Point of Care

2017 ◽  
Vol 23 (3) ◽  
pp. 268-281 ◽  
Author(s):  
Ajay Kumar Jha ◽  
Vishwas Malik
Keyword(s):  
Mitral Regurgitation ◽  
Ejection Fraction ◽  
Clinical Decision Making ◽  
Artery Bypass ◽  
Postoperative Outcome ◽  
Numerical Data ◽  
Left Ventricular ◽  
Ischemic Mitral Regurgitation ◽  
Left Ventricular Dyssynchrony ◽  
Reduced Ejection Fraction

Anatomical, functional, and pathophysiologic mechanisms of ischemic mitral regurgitation (IMR) are markedly different from the primary mitral regurgitation. The older and ubiquitous cutoff of EROA (effective regurgitant orifice area) and Rvol (regurgitant volume) for IMR has been reinstated in the new guideline after a brief hiatus. There had always been a lack of good-quality evidence for its introduction for guiding IMR severity in the previous guideline, and we still do not have quality evidences that could justify its reintroduction. Unlike primary MR, IMR is usually associated with reduced ejection fraction. Therefore, it appears unrealistic to keep the similar cutoff for primary MR and IMR. The cutoff of severity can be modified according to projected values of Rvol normalized to ejection fraction and EROA normalized to Rvol. In addition, the treatment outcome in these patients is determined by factors (left ventricular dyssynchrony, annular dilatation, tenting area, tenting height, tenting volume, and myocardial viability) other than the simple grading. In this review article, a series of graph have been constructed from the numerical data derived from the literatures on IMR to depict the relationship between EROA, Rvol, left ventricular end diastolic volume, and ejection fraction in order to obtain a reasonable projection formula for EROA and Rvol. Furthermore, a management algorithm has been proposed for patients with IMR undergoing coronary artery bypass grafting based on echocardiographic predictors that influence the postoperative outcome.

Modification of sodium channel currents by lanthanum and lanthanide ions in human heart cells

1987 ◽  
Vol 65 (4) ◽  
pp. 591-597 ◽  
Author(s):  
J. Omar Bustamante
Keyword(s):  
Sodium Channel ◽  
Time Constant ◽  
Human Heart ◽  
Sodium Current ◽  
Lanthanide Ions ◽  
Original Position ◽  
Heart Cell ◽  
Heart Cells ◽  
Extracellular Side ◽  
Channel Currents

I examined the effects of 100 μM extracellular lanthanum and lanthanide ions on the fast transmembrane sodium channel currents of human heart cell segments. The experiments were conducted under control of the transmembrane electrical and chemical gradients. Lanthanum and lanthanide ion exposure decreased the amplitude and increased the inactivation time constant of the sodium current. Only a transient increase occurred for the activation time constant of the sodium current. The dependence of peak sodium current on excitatory and holding potentials (steady-state activation and inactivation curves, respectively) was transiently shifted to less negative potentials during the first 3 min of exposure, as if these cations were momentarily neutralizing the effective negative charges at the extracellular side of the membrane. The curves then returned to their original position and only the inactivation curves continued shifting progressively towards a limit at more negative membrane potentials. Membrane capacitance was always reduced and this may explain these late effects in terms of changes in membrane dielectric properties and free and bound charges, in addition to traditional screening and binding concepts. These effects were related to the electronic structure of these ions.

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.

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