Concealed positive force-frequency relationships in rat and mouse cardiac muscle revealed by ryanodine

1986 ◽  
Vol 251 (6) ◽  
pp. H1106-H1110 ◽  
Author(s):  
P. Stemmer ◽  
T. Akera
Keyword(s):  
Guinea Pig ◽  
Cardiac Muscle ◽  
Negative Inotropic Effect ◽  
Ion Concentration ◽  
Mouse Heart ◽  
Force Frequency ◽  
Frequency Relationship ◽  
Negative Relationships ◽  
Modest Effect ◽  
Positive Force

Increases in stimulation frequency between 0.3 and 2 Hz decrease developed tension in rat, seemingly inconsistent with the explanation that an elevation of intracellular Na+-ion concentration is responsible for the positive force-frequency relationships observed in most species. Thus the force-frequency relationships were reevaluated in isolated atrial muscle of rat and mouse heart that show negative relationships, comparing them with ferret and guinea pig that show positive relationships. Ryanodine (2 nM, 45-min exposure) markedly reduced potentiated postrest contractions in all four species and caused a marked negative inotropic effect especially at low stimulation frequencies in rat and mouse, a moderate effect in ferret, but only a modest effect in guinea pig. In the presence of ryanodine, all four species showed positive force-frequency relationships. These results indicate that activator calcium in rat, mouse, and ferret cardiac muscle has a large ryanodine-sensitive component that shows a negative force-frequency relationship, masking a component for positive force-frequency relationships that exists in all species.

Action potential duration and force-frequency relationship in isolated rabbit, guinea pig and rat cardiac muscle

1996 ◽  
Vol 166 (2) ◽  
pp. 150-155 ◽  
Author(s):  
P. Szigligeti ◽  
C. Pankucsi ◽  
T. B�ny�sz ◽  
A. Varr� ◽  
P. P. N�n�si
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Cardiac Muscle ◽  
Action Potential Duration ◽  
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.

Effects of rate and rhythm on contraction of rat papillary muscle

1959 ◽  
Vol 197 (6) ◽  
pp. 1199-1204 ◽  
Author(s):  
Brian F. Hoffman ◽  
John J. Kelly
Keyword(s):  
Cardiac Muscle ◽  
Papillary Muscle ◽  
Ionic Composition ◽  
Force Frequency ◽  
Progressive Decrease ◽  
Plasma Epinephrine ◽  
Perfusion Medium ◽  
Frequency Relationship ◽  
Rat Papillary Muscle ◽  
Isolated Rat

The unusual relationship between frequency of contraction and tension developed by the isolated rat papillary muscle has been studied in detail. The progressive decrease in tension with increasing rate is unrelated to the size or weight of the muscle and is not changed by alterations in the ionic composition of the perfusion medium. The force-frequency relationship is also unchanged by addition of plasma, epinephrine or digitalis to the perfusion medium. Rat papillary muscle is similar to other preparations of cardiac muscle with respect to recovery of contractility and the development of rest contractions and postextrasystolic potentiation.

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 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.

Negative inotropic effect of extracellular calcium buffering in cardiac muscle

1987 ◽  
Vol 252 (2) ◽  
pp. C248-C252 ◽  
Author(s):  
Y. Shimoni ◽  
S. Ginsburg
Keyword(s):  
Guinea Pig ◽  
Cardiac Muscle ◽  
Heart Muscle ◽  
Calcium Concentration ◽  
Negative Inotropic Effect ◽  
Intracellular Acidosis ◽  
Calcium Buffering ◽  
The Mean ◽  
Frog Atrium ◽  
External Calcium

Heart muscle contracts more vigorously when calcium levels are raised. A transient depletion of calcium from restricted extracellular spaces occurs with each contraction. We decided to maintain the concentration of this ion at a constant level by using an external calcium buffering system. It was found that buffering calcium at a millimolar level (using citrate as a buffer) caused a decrease, rather than an increase in the strength of contraction. The mean reduction in peak tension was by 27% in guinea pig and by 50.5% in frog atrium. This finding is analyzed; its most plausible explanation is the hypothesis that the buffer dissipates a calcium inhomogeneity, consisting of a higher calcium concentration adjacent to the membrane. Alternative interpretations such as intracellular acidosis, were tested experimentally and ruled out.

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