Na+ channel modulation and force-frequency relationship in human myocardium

1997 ◽  
Vol 355 (6) ◽  
pp. 727-732 ◽  
Author(s):  
Jochen Müller-Ehmsen ◽  
Klara Brixius ◽  
Costas Schulze ◽  
R. H. G. Schwinger
1995 ◽  
Vol 82 (6) ◽  
pp. 1456-1462. ◽  
Author(s):  
Ulrich Schmidt ◽  
Robert H. G. Schwinger ◽  
Michael Bohm

Background The terminally failing human myocardium exerts a negative force-frequency relationship (FFR), whereas a positive FFR occurs in nonfailing myocardium. To study the possibility of pharmacologically influencing this defect of the failing human heart, the effect of halothane on the basal FFR and the FFR in the presence of isoproterenol and ouabain was investigated. Methods Experiments were performed on isolated, electrically driven (0.5-2 Hz, 37 degrees C, Ca2+ 1.8 mmol/l) ventricular preparations. Myocardium from human failing and nonfailing hearts was obtained at cardiac surgery. To further characterize the studied myocardium, the positive inotropic effect of isoproterenol and the density of beta-adrenoceptors were measured using the radioligand 125I-CYP. Results Halothane produced a negative inotropic effect. The anesthetic (0.38 mmol/l) reversed the negative FFR in failing myocardium, antagonized the effect of isoproterenol (0.1 mumol/l) on FFR, and restored the FFR in the presence of ouabain. Conclusions Halothane restores the FFR in human failing myocardium possibly by influencing the intracellular Ca2+ homeostasis. These findings provide evidence that pharmacologic interventions, e.g., during anesthesia, may influence contractility also as a result of a depressed or enhanced FFR.


2018 ◽  
Vol 6 (20) ◽  
pp. e13898 ◽  
Author(s):  
Jae-Hoon Chung ◽  
Benjamin D. Canan ◽  
Bryan A. Whitson ◽  
Ahmet Kilic ◽  
Paul M. L. Janssen

1999 ◽  
Vol 1 (2) ◽  
pp. 177-186 ◽  
Author(s):  
Achim Meissner ◽  
Jiang-Yong Min ◽  
Nils Haake ◽  
Stephan Hirt ◽  
Rüdiger Simon

2000 ◽  
Vol 278 (6) ◽  
pp. H1924-H1932 ◽  
Author(s):  
Götz Münch ◽  
Birgit Bölck ◽  
Klara Brixius ◽  
Hannes Reuter ◽  
Uwe Mehlhorn ◽  
...  

The present investigation addresses whether protein expression and function of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a) and phospholamban (PLB) correlate in failing and nonfailing human myocardium. SERCA2a activity and protein expression, PLB phosphorylation, and the force-frequency relationship (FFR) have been determined in right atrium (RA) and left ventricle (LV) from nonfailing (NF, n = 12) and terminally failing [dilated cardiomyopathy (DCM), n = 12] human hearts. Only in LV of DCM hearts was SERCA2a activity significantly decreased [maximal turnover rate ( V max) = 196 ± 11 and 396 ± 30 nmol ⋅ mg− 1 ⋅ min− 1in LV and RA, respectively], whereas protein expression of SERCA2a in the different chambers was unchanged in NF (3.9 ± 0.3 and 3.2 ± 0.4 densitometric units in LV and RA, respectively) and DCM hearts (4.8 ± 0.8 and 3.4 ± 0.1 densitometric units in LV and RA, respectively). Phosphorylation of PLB was higher in LV than in RA in NF (Ser16: 180.5 ± 19.0 vs. 56.8 ± 6.0 densitometric units; Thr17: 174.6 ± 11.2 vs. 37.4 ± 8.9 densitometric units) and DCM hearts (Ser16: 132.0 ± 5.4 vs. 22.4 ± 3.5 densitometric units; Thr17: 131.2 ± 10.9 vs. 9.2 ± 2.4 densitometric units). SERCA2a function, but not protein expression, correlated well with the functional parameters of the FFR in DCM and NF human hearts. Regulation of SERCA2a function depends on the phosphorylation of PLB at Ser16 and Thr17. However, direct SERCA2a regulation might also be affected by an unknown mechanism.


1993 ◽  
Vol 126 (4) ◽  
pp. 1018-1021 ◽  
Author(s):  
Robert H.G. Schwinger ◽  
Michael Böhm ◽  
Rainer Uhlmann ◽  
Ulridi Schmid ◽  
Peter Übertuhr ◽  
...  

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Jae‐Hoon Chung ◽  
Benjamin Canan ◽  
Bryan Whitson ◽  
Ahmet Kilic ◽  
Peter Mohler ◽  
...  

2020 ◽  
Vol 11 ◽  
Author(s):  
Maha Abu-Khousa ◽  
Dominik J. Fiegle ◽  
Sophie T. Sommer ◽  
Ghazali Minabari ◽  
Hendrik Milting ◽  
...  

2002 ◽  
Vol 282 (1) ◽  
pp. H131-H137 ◽  
Author(s):  
Klara Brixius ◽  
Sebastian Reicke ◽  
Robert H. G. Schwinger

Levosimendan has been reported to increase cardiac Ca2+ sensitivity, thereby not enhancing intracellular Ca2+ or diastolic tension. This may be advantageous for the treatment of heart failure patients. Therefore, the present study investigates the mode of action of levosimendan in both failing and nonfailing (NF) human myocardium. The effects of levosimendan on contractile force, Ca2+ transient (fura 2), and the force-frequency relationship (0.5–3 Hz) were studied in left ventricular terminally failing [dilated cardiomyopathy (DCM; n = 18)] and nonfailing (NF) myocardium (donor hearts, n = 6). Levosimendan (0.03–10 μmol/l) increased contractile force in NF (EC50: 0.38 μmol/l). In left ventricular failing myocardium, levosimendan only increased force after prestimulation with isoprenaline (0.1 μmol/l, EC50levosimendan: 0.062 μmol/l) or after elevation of the extracellular Ca2+ concentration from 1.8 to 3.2 mmol/l. After application of isoprenaline, levosimendan shortened relaxation and contraction kinetics. Levosimendan did not change the systolic Ca2+ transient but it improved the force-frequency relationship in DCM. In conclusion, levosimendan improves contraction in failing human myocardium under conditions with already increased intracellular Ca2+.


2017 ◽  
Vol 30 (8) ◽  
pp. 797-806 ◽  
Author(s):  
Silvia V. Alvarez ◽  
Etienne Fortin-Pellerin ◽  
Mohammed Alhabdan ◽  
Jesus S. Lomelin ◽  
Michal Kantoch ◽  
...  

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