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Heart valves have long been considered exclusively passive structures that open and close in response to changes in transvalvular pressure during the cardiac cycle. Although this is partly true, recent evidence suggests that valve...
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Heart valves have long been considered exclusively passive structures that open and close in response to changes in transvalvular pressure during the cardiac cycle. Although this is partly true, recent evidence suggests that valves are far more sophisticated structures. Microscopic examination of heart valves reveals a complex network of endo-thelial cells, interstitial cells, an extracellular matrix and a rich network of intrinsic nerves. The distribution of these nerve networks varies between the four valves, but is remarkably conserved between species. The present review will focus mainly on aortic valve innervation for several reasons: it is most commonly involved in disease processes, it lies in a unique hemodynamic environment and is exposed to extreme mechanical forces. These nerves are likely to play a significant role in the modulation of aortic valve structure and function and its adaptation to different hemodynamic and humoral conditions. The objectives of this review are first to describe the anatomy of aortic valve innervation, then detail the functional significance of innervation to the valve and finally make the case for the clinical relevance of understanding the neural control of aortic valves and its potential pharmacologic implications.
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摘要 :
Heart valves have long been considered exclusively passive structures that open and close in response to changes in transvalvular pressure during the cardiac cycle. Although this is partly true, recent evidence suggests that valve...
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Heart valves have long been considered exclusively passive structures that open and close in response to changes in transvalvular pressure during the cardiac cycle. Although this is partly true, recent evidence suggests that valves are far more sophisticated structures. Microscopic examination of heart valves reveals a complex network of endo-thelial cells, interstitial cells, an extracellular matrix and a rich network of intrinsic nerves. The distribution of these nerve networks varies between the four valves, but is remarkably conserved between species. The present review will focus mainly on aortic valve innervation for several reasons: it is most commonly involved in disease processes, it lies in a unique hemodynamic environment and is exposed to extreme mechanical forces. These nerves are likely to play a significant role in the modulation of aortic valve structure and function and its adaptation to different hemodynamic and humoral conditions. The objectives of this review are first to describe the anatomy of aortic valve innervation, then detail the functional significance of innervation to the valve and finally make the case for the clinical relevance of understanding the neural control of aortic valves and its potential pharmacologic implications.
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Most children with aortic valve disease present with isolated aortic regurgitation or stenosis, in which case valve repair is often possible, thus delaying or eliminating the need for valve replacement. In the child with mixed aor...
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Most children with aortic valve disease present with isolated aortic regurgitation or stenosis, in which case valve repair is often possible, thus delaying or eliminating the need for valve replacement. In the child with mixed aortic stenosis and regurgitation, repair is often more complex and less successful, requiring replacement of the valve and/or root. Several elements require careful consideration in children including growth potential of the child, risk of future reoperations, and the need for anticoagulation. A formal decision tree in this context is difficult because of the high variability between patients and pathologies and the lack of prospective randomized data. Nevertheless, we here present our approach to the child with mixed aortic stenosis and regurgitation, exploring the various options and explaining our favored approach.
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AimsIvabradine (Iva) has shown beneficial structural and functional effects in clinical and experimental heart failure (HF), but its action in combination with mechanical unloading (MU), such as during treatment with left ventricu...
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AimsIvabradine (Iva) has shown beneficial structural and functional effects in clinical and experimental heart failure (HF), but its action in combination with mechanical unloading (MU), such as during treatment with left ventricular assist devices (LVAD), is unknown. The aim of this study was to investigate the effects of Iva during MU, in a rodent model of HF.Methods and resultsWe studied the chronic effects (4 weeks) of Iva (10 mg/kg/day) alone and in combination with MU [induced by heterotopic abdominal heart transplantation (HATx)] on whole-heart and cellular structure, function, and excitation-contraction (E-C) coupling in a rodent (rat) model of HF, 12 weeks post-left coronary artery (LCA) ligation. Effects of Iva were compared with those of β-blockade using metoprolol [(Met), 250 mg/kg/day]. Iva, but not Met, reversed myocardial fibrosis, alone and in combination with MU. MU-induced restoration of deranged E-C coupling was enhanced by Iva to a greater extent than Met: both Iva and Met enhanced the recovery of the Ca2+ transient amplitude and the sarcoplasmic reticulum (SR) Ca2+ content, but Iva alone maintained MU-induced normalization of L-type Ca2+ current and t-tubule abnormalities. Met prevented MU-induced reduction in the myocardial size (myocardial atrophy); Iva had no effect on this parameter.ConclusionIva shows beneficial structural and E-C coupling effects during MU: Iva reverses myocardial fibrosis and enhances the restoration of deranged E-C coupling, displaying more beneficial effects than that of Met. These results suggest that Iva may prove effective in enhancing functional recovery in heart failure patients receiving LVAD therapy.
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BACKGROUND: Intracoronary injection of bone marrow mononuclear cells (BMMNC) is a common clinical protocol of cell transplantation for heart disease, but poor engraftment of donor cells in the heart, which will limit its therapeut...
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BACKGROUND: Intracoronary injection of bone marrow mononuclear cells (BMMNC) is a common clinical protocol of cell transplantation for heart disease, but poor engraftment of donor cells in the heart, which will limit its therapeutic efficacy, is a major issue. Initial "retention" (endothelial adherence and/or extravasation) of BMMNC immediately after intracoronary injection is a key step toward successful engraftment; however, this event has not been fully characterized. The aim of this study is to quantitatively clarify the frequency of "retention" of BMMNC after intracoronary injection, determine the impact of prior induction of ischemia-reperfusion injury on "retention" efficiency, and elucidate the underlying mechanisms focusing on adhesion molecule-mediated cell-cell interactions. METHODS: One million BMMNC collected from green fluorescent protein (GFP)-transgenic mice were injected into the coronary arteries of syngeneic wild-type mouse hearts under Langendorff perfusion. Retention efficiency was quantitatively estimated from the GFP-positive cell number flushed out into the coronary effluent. RESULTS: Whereas only 13.3 +/- 1.2% of injected BMMNC were retained into normal hearts, prior induction of 30-minute ischemia and 30-minute reperfusion increased the retention efficiency to 36.5 +/- 1.6% (p < 0.05, n = 8). Immunoconfocal observation further confirmed this enhanced retention after ischemia-reperfusion. Noticeably, the enhanced retention efficiency after ischemia-reperfusion treatment was diminished by administration of anti-P-selectin antibody (8.3 +/- 0.8%, p < 0.05), but was not affected by inhibiting intercellular adhesion molecule-1 (39.6 +/- 3.3%) or vascular cell adhesion molecule-1 (43.9 +/- 2.9%). CONCLUSIONS: Retention efficiency of intracoronary-injected BMMNC was poor in a model of isolated, crystalloid-perfused murine hearts. An antecedent period of global ischemia-reperfusion increased the retention via P-selectin-dependent BMMNC-endothelial interaction.
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The intrinsic capacity of the heart to beat 'spontaneously'-even after extraction from the body-has attracted the attention of scientists and physicians for many hundreds of years, including Galen in the 2nd century AD, and contin...
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The intrinsic capacity of the heart to beat 'spontaneously'-even after extraction from the body-has attracted the attention of scientists and physicians for many hundreds of years, including Galen in the 2nd century AD, and continues to do so today. Apart from general and scientific curiosity, this property has extremely important clinical implications, since heart rate and its control have been shown to have strong prognostic and therapeutic values. The publication of results of SHIFT (systolic heart failure treatment with the I_f inhibitor ivabradine trial) is the latest example of the value that research on the mechanisms and control of heart rate has in influencing care of patients with heart failure and is an important paradigm of translational research.
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Objectives: This study was undertaken to explore aspects of the hemodynamic function of different biologic tissue aortic valve root replacements. We set out to image and display the spatiotemporal distributions of axially directed...
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Objectives: This study was undertaken to explore aspects of the hemodynamic function of different biologic tissue aortic valve root replacements. We set out to image and display the spatiotemporal distributions of axially directed blood velocity through the aortic root. Methods: The flow velocities through a plane transecting the aortic root were measured by 2-dimensional cine phase-contrast magnetic resonance velocity mapping in 44 subjects: 29 patients who had undergone aortic root replacement approximately 10 years previously (13 autografts, 10 stentless xenografts, and 6 homografts) and 15 healthy control subjects. With cine as well as velocity images, aortic sinus dimensions, effective orifice area, and several velocity parameters were measured. Color-coded plots of velocity relative to the sinus cross sections and velocity-time plots were used to compare spatiotemporal distributions of velocity. Results: Peak flow velocity was similar between the autografts (102 ± 28.0 cm/s) and control valves (119 ± 20.0 cm/s) but was higher in xenografts (167 ± 36.0 cm/s) and homografts (206 ± 91.0 cm/s). These measurements showed an inverse relationship with the effective orifice area (7.27 ± 0.20, 4.24 ± 0.81, 3.37 ± 0.32, and 3.28 ± 0.87 cm 2, respectively). Autograft peak flow velocity showed no significant difference from control valve peak flow velocity, despite larger root dimensions (P < .001). The graphic displays provided further spatiotemporal information. Conclusions: Peak velocities and spatiotemporal flow patterns depend on the type of valve substitute. In the parameters measured, autograft replacements differed least from normal aortic valves.
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Collagen fibers are essential components of tissues, which are highly conserved across the animal kingdom and could be extremely useful in tissue engineering. The formation of these macromolecular fibers depends on molecular inter...
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Collagen fibers are essential components of tissues, which are highly conserved across the animal kingdom and could be extremely useful in tissue engineering. The formation of these macromolecular fibers depends on molecular interactions-based self-assembly of the basic building blocks of collagen called tropocollagens. Several attempts to produce biomimetic collagen have been described, however the best method to achieve the optimal material for tissue engineering has not been established. Here, we describe a bottom-up approach to design two computationally mutated molecular models that use non-covalent interactions to cross-link triple helices of tropocollagen molecules and thus promote self-association. Implementing a graph theory approach in the software FIRST reveals the hotspots that are crucial for the overall rigidity of the supramolecular helical structures and the remaining non-hotspots available for mutations. The mutated models were further decorated with GFOGER, a known collagen cell binding motif, to depict a biofunctional model. In addition to their recognized role of cell binding, the charged residues of the binding motif appeared to enhance further the supramolecular helical association. These findings could help to produce biomimetic collagen for biomedical applications.
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Although recent progress in cardiovascular tissue engineering has generated great expectations for the exploitation of stem cells to restore cardiac form and function, the prospects of a common mass-produced cell resource for clin...
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Although recent progress in cardiovascular tissue engineering has generated great expectations for the exploitation of stem cells to restore cardiac form and function, the prospects of a common mass-produced cell resource for clinically viable engineered tissues and organs remain problematic. The refinement of stem cell culture protocols to increase induction of the cardiomyocyte phenotype and the assembly of transplantable vascularized tissue are areas of intense current research, but the problem of immune rejection of heterologous cell type poses perhaps the most significant hurdle to overcome. This article focuses on the potential advantages and problems encountered with various stem cell sources for reconstruction of the damaged or failing myocardium or heart valves and also discusses the need for integrating advances in developmental and stem cell biology, immunology and tissue engineering to achieve the full potential of cardiac tissue engineering. The ultimate goal is to produce ‘off-the-shelf’ cells and tissues capable of inducing specific immune tolerance.
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