1,721,169 research outputs found
Pacing beyond rhythm – improving myocardial function by tickling the heart electrically?
No full textHeterogeneous transmural gene expression of calcium-handling proteins and natriuretic peptides in the failing human heart
No full textObjective: Human heart failure is associated with a disturbed intracellular calcium (Ca2+) homeostasis. In this regard, ventricular wall stress is considered to be a determinant for expression of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a). In the present study, we analyzed the transmural protein and/or mRNA levels of SERCA2a, other Ca2+-handling proteins, and of atrial and brain natriuretic peptides (ANP and BNP) in the human heart. Methods: Subepicardial (epi), midmyocardial (mid), and subendocardial (endo) sections of the left ventricular free wall from end-stage failing (n=17) and nonfailing (n=5) human hearts were analyzed by Western blot for immunoreactive protein levels of SERCA2a, phospholamban (PLN), and calsequestrin (CS). Subepi- and subendocardial sections were analyzed by Northern blot for steady-state mRNA levels of SERCA2a, Na+-Ca2+ exchanger (NCX1), ANP, and BNP. Results: SERCA2a protein and mRNA levels were reduced by 40±5% (P<0.01) and 25±7% (P<0.05) in endo compared to epi in the failing heart and by 27±14% and 16±12% (non-significant) in the nonfailing heart, respectively. PLN protein levels were reduced by 23±6% (P<0.05) in endo compared to epi in the failing heart and by 17±25% (non-significant) in the nonfailing heart, whereas CS protein levels and NCX1 mRNA levels were similar across the left ventricular wall. Strikingly, in the failing heart, both BNP and ANP mRNA levels were upregulated predominantly in endo. Conclusions: In the failing human heart, SERCA2a and PLN, as well as natriuretic peptides but not CS and NCX1 are differentially expressed across the left ventricular wall, implicating (1) different susceptibility of subendocardium and subepicardium to factors affecting expression of these proteins and (2) differences in regulation of the distinct calcium-cycling proteins
Low‐flow/low‐gradient aortic stenosis—Still a diagnostic and therapeutic challenge
No full textAortic stenosis (AS) is the most frequently observed valvular heart disease. During the symptomatic stage, the rate of death increases dramatically, so that a precise diagnostic approach is taken to guide therapeutic options. Of patients with severe AS, 30% to 50% present with low‐flow/low‐gradient AS (LF/LGAS) status. This review focuses on LF/LGAS and the best diagnostic and therapeutic management in either classic LF/LGAS with reduced left ventricular ejection fraction (LVEF) or paradoxical LF/LGAS with preserved LVEF. Current literature demonstrates that in classic LF/LGAS it is crucial to rule out a pseudo‐severe AS, because reduced LVEF may result in an incomplete opening of the valve. This can be done by low‐dose dobutamine stress echocardiography. Classic LF/LGAS has poor clinical outcomes when managed conservatively; therefore, surgical or interventional aortic valve replacement should be performed. In paradoxical LF/LGAS, the LVEF is preserved (>50%), but impaired filling of the concentric hypertrophied ventricle leads to reduced stroke volume. Therefore, diagnostic and therapeutic decisions in paradoxical LF/LGAS are even more challenging. It is a heterogeneous disease entity, and it is crucial to rule out any diagnostic errors because numerous potential confounders might lead to misdiagnosis. As in classic stenosis, pseudo‐severe stenosis must be ruled out as well. Evaluation via multidetector computed tomography or transesophageal echocardiography can help to evaluate the morphologic alterations of the valve (eg, calcification). Further studies are necessary to understand this disease entity and to evaluate the optimal diagnostic and therapeutic approach for these patients
Secreted-Frizzled-Related Protein 5 Modulates Calcium Handling in Human Ipsc-Cardiomyocytes
No full textP3829 Antiarrhythmic effects of Sacubitrilat (LBQ657) on Ca2+ homeostasis in ventricular cardiomyocytes
No full textP5998The Phosphodiesterase 4D interacting protein averts volume overload - but not pressure overload-induced pathological myocardial remodeling
No full textAbstract 678: microRNA 146a Reduces Activity of Matrix-Metalloproteinases in the Context of Arterial Stiffness
No full textFrequency-dependence of the slow force response
No full textStretch induces biphasic inotropic effects in mammalian myocardium. A delayed component (slow force response, SFR) has been demonstrated in various species, however, experimental conditions varied and the underlying mechanisms are controversial. The physiological relevance of the SFR is poorly understood. Experiments were performed in ventricular muscle strips from failing human hearts and non-failing rabbit hearts. Upon stretch, twitch force was assessed at basal conditions (1Hz, 37 C) and after changing stimulation frequency with and without blockade of the Na(+)/H(+)-exchanger-1 (NHE1) or reverse-mode Na+/Ca+-exchange (NCX). Action potential duration (APD) was assessed using floating electrodes. Low stimulation rates (0.2Hz) potentiated and higher stimulation rates (2 and 3Hz) reduced the SFR. The extent of SFR inhibition by NHE1 or NCX inhibition was not affected by stimulation rate. APD decreased at 0.2Hz but was not altered at higher stimulation rates. The data demonstrate frequency-dependence of the SFR with greater positive inotropic effects at lower stimulation rates. Subcellular mechanisms underlying the SFR are not fundamentally affected by stimulation rate. The SFR may have more pronounced physiological effects at lower heart rates
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