scholarly journals Force-frequency relationship and early relaxation kinetics are preserved upon sarcoplasmic blockade in human myocardium

2018 ◽  
Vol 6 (20) ◽  
pp. e13898 ◽  
Author(s):  
Jae-Hoon Chung ◽  
Benjamin D. Canan ◽  
Bryan A. Whitson ◽  
Ahmet Kilic ◽  
Paul M. L. Janssen
Keyword(s):  
Human Myocardium ◽  
Force Frequency ◽  
Relaxation Kinetics ◽  
Frequency Relationship

scholarly journals Force‐frequency Relationship and Early Relaxation Kinetics Are Preserved Upon SR Blockade in Human Myocardium

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Jae‐Hoon Chung ◽  
Benjamin Canan ◽  
Bryan Whitson ◽  
Ahmet Kilic ◽  
Peter Mohler ◽  
...  
Keyword(s):  
Human Myocardium ◽  
Force Frequency ◽  
Relaxation Kinetics ◽  
Frequency Relationship

Halothane Restores the Altered Force-Frequency Relationship in Failing Human Myocardium

1995 ◽  
Vol 82 (6) ◽  
pp. 1456-1462. ◽  
Author(s):  
Ulrich Schmidt ◽  
Robert H. G. Schwinger ◽  
Michael Bohm
Keyword(s):  
Cardiac Surgery ◽  
Human Heart ◽  
Positive Inotropic Effect ◽  
Negative Inotropic Effect ◽  
Human Myocardium ◽  
Inotropic Effect ◽  
Force Frequency ◽  
Beta Adrenoceptors ◽  
Frequency Relationship

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.

scholarly journals Dantrolene sodium improves the force-frequency relationship and β-adrenergic responsiveness in failing human myocardium

1999 ◽  
Vol 1 (2) ◽  
pp. 177-186 ◽  
Author(s):  
Achim Meissner ◽  
Jiang-Yong Min ◽  
Nils Haake ◽  
Stephan Hirt ◽  
Rüdiger Simon
Keyword(s):  
Human Myocardium ◽  
Force Frequency ◽  
Dantrolene Sodium ◽  
Frequency Relationship

SERCA2a activity correlates with the force-frequency relationship in human myocardium

2000 ◽  
Vol 278 (6) ◽  
pp. H1924-H1932 ◽  
Author(s):  
Götz Münch ◽  
Birgit Bölck ◽  
Klara Brixius ◽  
Hannes Reuter ◽  
Uwe Mehlhorn ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Protein Expression ◽  
Right Atrium ◽  
Turnover Rate ◽  
Human Myocardium ◽  
Force Frequency ◽  
Unknown Mechanism ◽  
Plasmic Reticulum ◽  
Frequency Relationship ◽  
And Function

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.

scholarly journals Impact of heart rate on cross-bridge cycling kinetics in failing and nonfailing human myocardium

2019 ◽  
Vol 317 (3) ◽  
pp. H640-H647
Author(s):  
Jae-Hoon Chung ◽  
Nima Milani-Nejad ◽  
Jonathan P. Davis ◽  
Noah Weisleder ◽  
Bryan A. Whitson ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Human Myocardium ◽  
Force Frequency ◽  
Human Heart Failure ◽  
Relaxation Kinetics ◽  
Heart Rates ◽  
Cross Bridge ◽  
Maximal Activation

The force-frequency relationship (FFR) is an important regulatory mechanism that increases the force-generating capacity as well as the contraction and relaxation kinetics in human cardiac muscle as the heart rate increases. In human heart failure, the normally positive FFR often becomes flat, or even negative. The rate of cross-bridge cycling, which has been reported to affect cardiac output, could be potentially dysregulated and contribute to blunted or negative FFR in heart failure. We recently developed and herein use a novel method for measuring the rate of tension redevelopment. This method allows us to obtain an index of the rate of cross-bridge cycling in intact contracting cardiac trabeculae at physiological temperature and assess physiological properties of cardiac muscles while preserving posttranslational modifications representative of those that occur in vivo. We observed that trabeculae from failing human hearts indeed exhibit an impaired FFR and a reduced speed of relaxation kinetics. However, stimulation frequencies in the lower spectrum did not majorly affect cross-bridge cycling kinetics in nonfailing and failing trabeculae when assessed at maximal activation. Trabeculae from failing human hearts had slightly slower cross-bridge kinetics at 3 Hz as well as reduced capacity to generate force upon K+ contracture at this frequency. We conclude that cross-bridge kinetics at maximal activation in the prevailing in vivo heart rates are not majorly impacted by frequency and are not majorly impacted by disease. NEW & NOTEWORTHY In this study, we confirm that cardiac relaxation kinetics are impaired in filing human myocardium and that cross-bridge cycling rate at resting heart rates does not contribute to this impaired relaxation. At high heart rates, failing myocardium cross-bridge rates are slower than in nonfailing myocardium.

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
Keyword(s):  
Human Myocardium ◽  
Na Channel ◽  
Force Frequency ◽  
Channel Modulation ◽  
Frequency Relationship

Magnesium restores the altered force-frequency relationship in failing human myocardium

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

scholarly journals The Degree of t-System Remodeling Predicts Negative Force-Frequency Relationship and Prolonged Relaxation Time in Failing Human Myocardium

2020 ◽  
Vol 11 ◽  
Author(s):  
Maha Abu-Khousa ◽  
Dominik J. Fiegle ◽  
Sophie T. Sommer ◽  
Ghazali Minabari ◽  
Hendrik Milting ◽  
...  
Keyword(s):  
Relaxation Time ◽  
Human Myocardium ◽  
Force Frequency ◽  
Frequency Relationship ◽  
T System

Beneficial effects of the Ca2+ sensitizer levosimendan in human myocardium

2002 ◽  
Vol 282 (1) ◽  
pp. H131-H137 ◽  
Author(s):  
Klara Brixius ◽  
Sebastian Reicke ◽  
Robert H. G. Schwinger
Keyword(s):  
Heart Failure ◽  
Contractile Force ◽  
Left Ventricular ◽  
Human Myocardium ◽  
Force Frequency ◽  
Heart Failure Patients ◽  
Beneficial Effects ◽  
Intracellular Ca ◽  
Frequency Relationship ◽  
Contraction Kinetics

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+.

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