scholarly journals Strain Rate and Its Positive Force-Frequency Relationship: Further Evidence from a Premature Infant Cohort

2017 ◽  
Vol 30 (10) ◽  
pp. 1045-1046 ◽  
Author(s):  
Colm R. Breatnach ◽  
Phil T. Levy ◽  
Orla Franklin ◽  
Afif EL-Khuffash
Keyword(s):  
Strain Rate ◽  
Premature Infant ◽  
Force Frequency ◽  
Frequency Relationship ◽  
Positive Force

Strain Rate in Children and Young Piglets Mirrors Changes in Contractility and Demonstrates a Force-Frequency Relationship

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

Abstract 15596: Maturation of Hipsc-cm Electrophysiological and Contractile Function for Enhanced Sensitivity of Cardiac Safety Assays

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Heather B Hayes ◽  
Anthony M Nicolini ◽  
Colin Arrowood ◽  
Daniel Millard
Keyword(s):  
Contractile Function ◽  
Induced Pluripotent Stem Cell ◽  
Force Frequency ◽  
Cardiac Safety ◽  
Electrophysiological Response ◽  
Mechanical Conditioning ◽  
Enhanced Sensitivity ◽  
Frequency Relationship ◽  
Positive Force

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have significantly advanced in vitro cardiac safety and disese modeling, yet remain an immature representation of human myocytes. Electrical or mechanical conditioning of hiPSC-CMs facilitates functional maturation, as measured by a positive force-frequency relationship, but current in vitro protocols require 2-4 weeks of conditioning. Using array-based contractility and local electrical stimulation, we detected functionally mature phenotypes and compound responses in hiPSC-CMs after only 48 hours of chronic pacing. To mature cardiomyocytes, hiPSC-CMs were cultured on 24- and 96-well MEA plates with a dedicated stimulation electrodes. Later, hiPSC-CMs were electrically or optically paced at 2Hz for 48 hours. Multimodal measures quantified contractile and electrophysiological responses to varied pacing rates and compound addition. After 48 hours of pacing, hiPSC-CMs displayed shortened repolarization timing compared to before chronic pacing (baseline: 423 +/- 21 ms; matured: 316 +/- 15 ms), without significant beat period changes (baseline: 1255 +/- 40 ms; matured: 1314 +/- 84 ms). Contractile beat amplitude was measured using array-based impedance during spontaneous beating and at increasing pacing rates (1, 1.2, 1.5, 2, and 2.5 Hz). Before chronic pacing, beat amplitude decreased with increasing pacing rate; after chronic pacing, the same wells displayed increased beat amplitudes with increasing pacing rate. The matured wells also showed enhanced sensitivity to positive inotropes, such as isoproterenol, digoxin, omecamtiv mecarbil, and dobutamine. Local extracellular action potentials (LEAP) further revealed altered electrophysiological response to ranolazine, a multichannel blocker. Unpaced control wells exhibited dose-dependent APD90 prolongation in response to ranolazine, whereas matured wells showed no APD90 change. Similar results were seen with 48 hour of optogenetic pacing at 2 Hz. Overall, hiPSC-CMs chronically paced for only 48 hours exhibited more mature functional phenotypes, including a positive force-frequnecy relationship, enhanced ionotrope sensitivity, and altered compound response.

scholarly journals Cardiotoxins from cobra Naja oxiana change the force of contraction and the character of rhythmoinotropic phenomena in the rat myocardium

2019 ◽  
Vol 487 (5) ◽  
pp. 578-583
Author(s):  
A. S. Averin ◽  
M. E. Astashev ◽  
T. V. Andreeva ◽  
V. I. Tsetlin ◽  
Yu. N. Utkin
Keyword(s):  
Positive Inotropic Effect ◽  
Stimulation Frequency ◽  
Inotropic Effect ◽  
Force Frequency ◽  
Rat Myocardium ◽  
Frequency Range ◽  
High Concentration ◽  
Irreversible Damage ◽  
Frequency Relationship ◽  
Positive Force

The study of the influence of cobra Naja oxiana cardiotoxins on the contractility of the rat papillary muscles and its rhythm-inotropic characteristics has that the presence of toxins induces a slight contractility decrease in the stimulation frequency range up to 0,1 Hz. In the stimulation frequency range from 0,1 to 0,5 Hz a positive inotropic effect is found. However, the positive inotropic effect is replaced by a negative one with further increase in the frequency up to 3 Hz. In the presence of cardiotoxins, the positive force-frequency relationship in the region of 1-3 Hz, characteristic of healthy rat myocardium, disappears and relationship becomes completely negative. L‑type calcium channel blocker nifedipine does not affect the changes induced by toxins, while a high concentration (10 mM) of calcium prevents the effects of cardiotoxins on the muscle. The results obtained show that the impairment of the force-frequency relationship occurs long before the development of irreversible damage in the myocardium and may be the first sign of the pathological action of cardiotoxins.

scholarly journals Positive force- and [Ca2+]i-frequency relationships in rat ventricular trabeculae at physiological frequencies

1999 ◽  
Vol 276 (1) ◽  
pp. H9-H18 ◽  
Author(s):  
Joanne Layland ◽  
Jonathan C. Kentish
Keyword(s):  
Isometric Force ◽  
Force Frequency ◽  
Dependent Protein Kinase ◽  
Low Frequencies ◽  
High Frequencies ◽  
Dependent Protein ◽  
Frequency Relationship ◽  
Relationship Of ◽  
Ventricular Trabeculae ◽  
Positive Force

The isometric force-frequency relationship of isolated rat ventricular trabeculae (diameter <250 μm) was examined at 24, 30, and 37°C at stimulation frequencies (0.1–12 Hz) encompassing the physiological range. Some muscles were microinjected with fura PE3 to monitor the diastolic and systolic intracellular concentration of Ca2+([Ca2+]i). At a near-physiological external Ca2+ concentration ([Ca2+]o) of 1 mM, a positive force-frequency relationship was demonstrated at all temperatures. The force-frequency relationship became negative at high frequencies (e.g., >6 Hz at 30°C) at 1 mM [Ca2+]oor at low frequencies at 8 mM [Ca2+]o. The twitch and Ca2+ transient became shorter as stimulation frequency increased; these changes were related to changes in systolic, rather than diastolic, [Ca2+]iand were not blocked by inhibitors of Ca2+/calmodulin-dependent protein kinase II. The positive force-frequency relationship of rat trabeculae was caused by a frequency-dependent loading of the sarcoplasmic reticulum (SR) with Ca2+. We suggest that at high frequencies, or under conditions of Ca2+ overload, this loading saturates. Processes that tend to decrease SR Ca2+ release will then predominate, resulting in a negative force-frequency relationship.

Ca2+ and Na+ in rat myocytes showing different force-frequency relationships

1991 ◽  
Vol 261 (5) ◽  
pp. C739-C750 ◽  
Author(s):  
J. E. Frampton ◽  
S. M. Harrison ◽  
M. R. Boyett ◽  
C. H. Orchard
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Time Course ◽  
Cell Types ◽  
Stimulation Frequency ◽  
Force Frequency ◽  
Rat Hearts ◽  
Rate Of Decline ◽  
Frequency Relationship ◽  
Positive Force ◽  
In Cells

Intracellular [Ca2+] ([Ca2+]i), intracellular Na+ activity (aiNa), and contraction have been monitored in single myocytes isolated from the ventricles of rat hearts. Some of these cells showed an increase in the size of the twitch as stimulation frequency was increased (positive force-frequency relationship), while others showed a decrease in the strength of contraction as the frequency of stimulation was increased (negative force-frequency relationship). In cells that showed a positive force-frequency relationship, increasing stimulation frequency resulted in increases in aiNa, diastolic [Ca2+]i, systolic [Ca2+]i, and the amount of Ca2+ that could be released from the sarcoplasmic reticulum by caffeine. The rate of decline of the [Ca2+]i transient and the twitch also increased as stimulation frequency was increased. In cells that showed a negative force-frequency relationship, increasing stimulation frequency had less effect on aiNa and had either no effect or decreased systolic [Ca2+]i with no change in the amount of Ca2+ that could be released from the sarcoplasmic reticulum using caffeine. The rate of relaxation of the [Ca2+]i transient and the twitch again increased as stimulation frequency increased. The pattern and time course of mechanical restitution was the same in both cell types. Although these data are essentially descriptive, it is consistent with the hypothesis that the final contractile response observed during changes of stimulation frequency may be dependent on how the Ca2+ loading of the preparation varies with stimulation frequency.

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