Contractile parameters and occurrence of alternans in isolated rat myocardium at supra-physiological stimulation frequency

2012 ◽  
Vol 302 (11) ◽  
pp. H2267-H2275 ◽  
Author(s):  
Jessica L. Slabaugh ◽  
Lucia Brunello ◽  
Sandor Gyorke ◽  
Paul M. L. Janssen
Keyword(s):  
Heart Rate ◽  
Steady State ◽  
Refractory Period ◽  
Striated Muscle ◽  
Stable Steady State ◽  
Maximal Heart Rate ◽  
Force Frequency ◽  
Mechanical Instability ◽  
Continuous Increase

The cardiac refractory period prevents the heart from tetanic activation that is typically used in noncardiac striated muscle tissue. To what extent the refractory period prevents successive action potentials to activate the excitation-contraction coupling process and contractile machinery at supra-physiological rates, such as those present during ventricular fibrillation, is unknown. Using multicellular trabeculae isolated from rat hearts, we studied amplitude and kinetics of contraction at rates well above the normal in vivo rat heart range. We show that even at twice the maximal heart rate of the rat, little or no mechanical instability is observed; twitch contractions are at steady state, albeit with an elevated active diastolic force. Although the amplitude of contraction increased within in vivo heart rates (positive force-frequency response), at frequencies beyond the maximal heart rate (10–30 Hz) a steady decline of contractile amplitude is observed. Not until 30 Hz do the majority of the isolated muscle preparations show mechanical alternans, where strong and weak beats alternate. Interestingly, unlike striated limb skeletal muscle, fusing of twitch contractions did not cause a continuous increase in peak force: at frequencies of 10 Hz and above, systolic force declines with relatively little elevation in diastolic force. Contractile kinetics continued to accelerate, from 1 Hz up to 30 Hz, whereas the relative speed of contraction and relaxation remained closely coupled, reflected by a singular linear relationship between the maximal and minimal derivative of force (dF/d t). We conclude that cardiac muscle can produce mechanically stable steady-state contractions at supra-physiological pacing rates, while these contractions continue to decline in amplitude and increase in diastolic force past maximal heart rate.

Temperature dependence of oxygen diffusion and consumption in mammalian striated muscle

1993 ◽  
Vol 264 (6) ◽  
pp. H1825-H1830 ◽  
Author(s):  
T. B. Bentley ◽  
H. Meng ◽  
R. N. Pittman
Keyword(s):  
Diffusion Coefficient ◽  
Steady State ◽  
Oxygen Diffusion ◽  
Striated Muscle ◽  
Effect Of Temperature ◽  
Retractor Muscle ◽  
Oxygen Solubility ◽  
Order Of Magnitude

This study investigated the effect of temperature on the oxygen diffusion coefficient (DO2) of hamster retractor muscle from 11 to 37 degrees C. DO2 was measured using a non-steady-state technique, whereas muscle O2 consumption (VO2) was estimated after steady state was reached. DO2 was 0.84 +/- 0.04 x 10(-5) cm2/s at 11 degrees C and rose exponentially to 2.41 +/- 0.19 x 10(-5) cm2/s at 37 degrees C, producing a temperature coefficient for DO2 of 4.60%/degrees C for this temperature range. To measure DO2 directly at 37 degrees C, it was necessary to inhibit tissue VO2 with Amytal. The DO2 measurements made at 37 degrees C were significantly higher than previously reported values, which had been based on extrapolations from lower temperatures (6). Further analysis suggests a possible transition in the diffusion pathway between 23 and 30 degrees C, resulting in a DO2 higher than that previously expected. This larger DO2, together with a recently published value of oxygen solubility (alpha) (21), results in an in vitro Krogh's diffusion coefficient (KO2) that is 2.4 times larger than that previously reported (24) and therefore significantly reduces an order of magnitude discrepancy between in vitro and estimated in vivo KO2 values (24). Muscle VO2 was 0.35 ml O2.min-1.100 g-1 at 11 degrees C and increased with temperature, resulting in an activation energy of the rate-limiting reaction from the Arrhenius equation of -10.5 kcal/mol between 11 and 30 degrees C.

A study of the physiological consequences of sympathetic denervation of the heart caused by the arterial switch procedure

2010 ◽  
Vol 20 (2) ◽  
pp. 150-158 ◽  
Author(s):  
Cecilia Falkenberg ◽  
Stefan Hallhagen ◽  
Krister Nilsson ◽  
Boris Nilsson ◽  
Ingegerd Östman-Smith
Keyword(s):  
Heart Rate ◽  
Coronary Flow ◽  
Arterial Switch Operation ◽  
Sympathetic Nerves ◽  
Heart Weight ◽  
Maximal Heart Rate ◽  
Response Curves ◽  
Arterial Switch

AbstractBackgroundThe arterial switch operation is the corrective operation for transposition of the great arteries, defined as the combination of concordant atrioventricular and discordant ventriculo–arterial connections, but there have been concerns about silent subendocardial ischaemia on exercise and coronary artery growth. The arterial switch divides the majority of the sympathetic nerves entering the heart; we have studied the effects of coronary flow and sensitivity to catecholamine stimulation in an animal model.MethodsA total of 10 piglets were operated on cardiopulmonary bypass with section and resuturing of aortic trunk, pulmonary artery and both coronary arteries, with 13 sham-operated controls. After 5–7 weeks of recovery, seven simulated switch survivors and 13 controls were studied.ResultsBasal heart rate was significantly higher in switch piglets: in vivo mean (standard deviation) 112 (12) versus sham 100 (10) beats per minute, (p = 0.042); in vitro (Langendorff preparation): 89 (9) versus sham 73 (8) beats per minute (p = 0.0056). In vivo maximal heart rate in response to epinephrine was increased in switch piglets, 209 (13) versus 190 (17) beats per minute (p = 0.044). In vitro dose–response curves to norepinephrine were shifted leftward and upwards (p = 0.0014), with an 80% increase in heart rate induced by 0.095 (0.053) norepinephrine micromole per litre perfusate in switch hearts versus 0.180 (0.035) norepinephrine micromole per litre (p = 0.023). Increase in coronary flow on norepinephrine stimulation and maximal coronary flow were significantly reduced in switch hearts: 0.3 (0.2) versus 0.8 (0.4) millilitre per gram heart weight (p = 0.045) and 2.5 (0.4) versus 3.1 (0.4) millilitre per gram heart (p = 0.030), respectively.ConclusionsA combination of increased intrinsic heart rate, increased sensitivity to chronotropic actions of norepinephrine, and a decreased maximal coronary flow creates potential for a mismatch between perfusion and energy demands.

Modulation of force-frequency relation by phospholamban in genetically engineered mice

1999 ◽  
Vol 276 (6) ◽  
pp. H2245-H2250 ◽  
Author(s):  
Vivek J. Kadambi ◽  
Nancy Ball ◽  
Evangelia G. Kranias ◽  
Richard A. Walsh ◽  
Brian D. Hoit
Keyword(s):  
Heart Rate ◽  
Myocardial Contractility ◽  
Left Ventricular ◽  
Atrial Pacing ◽  
Force Frequency ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Peak Rate ◽  
Genetically Engineered Mice ◽  
Frequency Relation

Phospholamban levels regulate cardiac sarcoplasmic reticulum Ca2+ pump activity and myocardial contractility. To determine whether and to what extent phospholamban modulates the force-frequency relation and ventricular relaxation in vivo, we studied transgenic mice overexpressing phospholamban (PLBOE), gene-targeted mice without phospholamban (PLBKO), and isogenic wild-type controls. Contractility was assessed by the peak rate of left ventricular (LV) isovolumic contraction (+dP/d t max), and diastolic function was assessed by both the peak rate (−dP/d t max) and the time constant (τ) of isovolumic LV relaxation, using a high-fidelity LV catheter. Incremental atrial pacing was used to generate heart rate vs. −dP/d t max(force-frequency) relations. Biphasic force-frequency relations were produced in all animals, and the critical heart rate (HRcrit) was taken as the heart rate at which dP/d t max was maximal. The average LV +dP/d t maxincreased in both PLBKO and PLBOE compared with their isogenic controls (both P < 0.05). The HRcrit for LV +dP/d t max was significantly higher in PLBKO (427 ± 20 beats/min) compared with controls (360 ± 18 beats/min), whereas the HRcrit in PLBOE (340 ± 30 beats/min) was significantly lower compared with that in isogenic controls (440 ± 25 beats/min). The intrinsic heart rates were significantly lower, and the HRcrit and the ±dP/d t max at HRcrit were significantly greater in FVB/N than in SvJ control mice. We conclude that 1) the level of phospholamban is a critical negative determinant of the force-frequency relation and myocardial contractility in vivo, and 2) contractile parameters may differ significantly between strains of normal mice.

Heart failure-associated alterations in troponin I phosphorylation impair ventricular relaxation-afterload and force-frequency responses and systolic function

2007 ◽  
Vol 292 (1) ◽  
pp. H318-H325 ◽  
Author(s):  
Kenneth C. Bilchick ◽  
Jennifer G. Duncan ◽  
Rajashree Ravi ◽  
Eiki Takimoto ◽  
Hunter C. Champion ◽  
...  
Keyword(s):  
Heart Rate ◽  
Protein Kinase ◽  
Troponin I ◽  
Systolic Function ◽  
Force Frequency ◽  
Rate Dependent ◽  
Isoproterenol Infusion ◽  
Relaxation Delay ◽  
Constitutive Phosphorylation

Recent studies have found that selective stimulation of troponin (Tn)I protein kinase A (PKA) phosphorylation enhances heart rate-dependent inotropy and blunts relaxation delay coupled to increased afterload. However, in failing hearts, TnI phosphorylation by PKA declines while protein kinase C (PKC) activity is enhanced, potentially augmenting TnI PKC phosphorylation. Accordingly, we hypothesized that these site-specific changes deleteriously affect both rate-responsive cardiac function and afterload dependence of relaxation, both prominent phenotypic features of the failing heart. A transgenic (TG) mouse model was generated in which PKA-TnI sites were mutated to mimic partial dephosphorylation (Ser22 to Ala; Ser23 to Asp) and dominant PKC sites were mutated to mimic constitutive phosphorylation (Ser42 and Ser44 to Asp). The two highest-expressing lines were further characterized. TG mice had reduced fractional shortening of 34.7 ± 1.4% vs. 41.3 ± 2.0% ( P = 0.018) and slight chamber dilation on echocardiography. In vivo cardiac pressure-volume studies revealed near doubling of isovolumic relaxation prolongation with increasing afterload in TG animals ( P < 0.001), and this remained elevated despite isoproterenol infusion (PKA stimulation). Increasing heart rate from 400 to 700 beats/min elevated contractility 13% in TG hearts, nearly half the response observed in nontransgenic animals ( P = 0.005). This blunted frequency response was normalized by isoproterenol infusion. Abnormal TnI phosphorylation observed in cardiac failure may explain exacerbated relaxation delay in response to increased afterload and contribute to blunted chronotropic reserve.

Cardiorespiratory Responses to Intermittent Exercise and Relaxation as Compared with Continuous Exercise

1994 ◽  
Vol 79 (3) ◽  
pp. 1071-1074 ◽  
Author(s):  
Barbara Day Lockhart ◽  
Tim Ruffin
Keyword(s):  
Heart Rate ◽  
Steady State ◽  
Intermittent Exercise ◽  
Maximal Heart Rate ◽  
Continuous Exercise ◽  
Cardiorespiratory Responses

Cardiorespiratory responses to intermittent exercise and relaxation were comparable to cardiorespiratory responses to continuous exercise. The time of workout and work loads were kept constant in both protocols. Even though in the intermittent exercise and relaxation protocol the 10 subjects rested nearly two-thirds of the duration of the workout, cardiorespiratory responses were similar to those which the same subjects attained while exercising continuously throughout the entire steady state workout at approximately 64% maximal heart rate.

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.

Predicting Maximal Lactate Steady State from Carminatti’s Shuttle Run Test in Soccer Players

2020 ◽  
Author(s):  
Lorival José Carminatti ◽  
Bruna Nunes Batista ◽  
Juliano Fernandes da Silva ◽  
Artur Ferreira Tramontin ◽  
Vitor Pereira Costa ◽  
...  
Keyword(s):  
Heart Rate ◽  
Steady State ◽  
Soccer Players ◽  
Maximal Heart Rate ◽  
Maximal Lactate Steady State ◽  
Incremental Test ◽  
Run Test ◽  
Peak Speed ◽  
Linear Regressions ◽  
Shuttle Run

AbstractThe objective of the present study was to determine the validity of Carminatti’s shuttle run incremental test–T-Car derived parameters in estimating the maximal lactate steady state determined in shuttle run format. Eighteen soccer players performed a T-Car test, and several trials to determine the maximal lactate steady state. From T-Car were derived the heart rate deflection point, peak speed, maximal heart rate and parameters resulting from percentage of peak measures. The validity was accessed by Bland-Altman plots, linear regressions, and two one-sided tests of equivalence analysis. The results showed the speed at 80.4% of T-Car peak speed, the heart rate deflection point and the 91.4% of maximal heart rate were equivalent to maximal lactate steady state (Mean difference; ±90% compatibility interval; −0.8; ±1.5%, −0.4; ±1.1%, and 0.0; ±2.7%, respectively). Additionally, peak speed during the T-Car test was a stronger predictor of maximal lactate steady state (MLSS [km/h]=2.57+0.65 × sPeak; r=0.82 [90% CI; 0.62–0.92], standard error of the estimate=3.6%; 90% CI ×/÷1.4). Therefore, soccer players can use the T-Car derived parameters as a noninvasive and practical alternative to estimate the specific maximal lactate steady state for soccer.

scholarly journals The regulatory principles of glycolysis in erythrocytes in vivo and in vitro. A minimal comprehensive model describing steady states, quasi-steady states and time-dependent processes

1976 ◽  
Vol 154 (2) ◽  
pp. 449-469 ◽  
Author(s):  
T A. Rapoport ◽  
R Heinrich ◽  
S M. Rapoport
Keyword(s):  
Steady State ◽  
Atp Synthesis ◽  
Steady States ◽  
Time Dependent ◽  
Glycolytic Flux ◽  
Stable Steady State ◽  
Time Interval ◽  
Fructose 1,6 Bisphosphate

A simple mathematical model for glycolysis in erythrocytes is presented which takes into account ATP synthesis and consumption. The system is described by four ordinary differential equations. Conditions in vivo are described by a stable steady state. The model predicts correctly the metabolite concentrations found in vivo. The parameters involved are in agreement with data on the separate steps. The metabolite changes found in pyruvate kinase-deficient erythrocytes and the species variations among erythrocytes from different animals are described satisfactorily. The roles of the enzymes in the control of metabolites and glycolytic flux are expressed in the form of a control matrix and control strengths [R. Heinrich & T.A. Rapoport (1974) Eur. J. Biochem. 42, 89-95] respectively. Erythrocytes from various species are shown to be adapted to a maximal ATP-consumption rate. The calculated eigenvalues reveal the pronounced time-hierarchy of the glycolytic reactions. Owing to the slowness of the 2,3-bisphospho-glycerate phosphatase reaction, quasi-steady states occur during the time-interval of about 0.5-2h incubation, which are defined by perturbed 2,3-bisphosphoglycerate concentrations. The theoretical predictions agree with experimental data. In the quasi-steady state the flux control is exerted almost entirely by the hexokinase-phosphofructokinase system. The model describes satisfactorily the time-dependent changes after addition of glucose to starved erythrocytes. The theoretical consequences are discussed of the conditions in vitro with lactate accumulation and the existence of a time-independent conservation quantity for the oxidized metabolites. Even in this closed system quasi-steady states occur which are characterized by approximately constant concentrations of all glycolytic metabolites except for the accumulation of lactate, fructose 1,6-bisphosphate and triose phosphate.

Changes in canine latissimus dorsi muscle during 24 wk of continuous electrical stimulation

1992 ◽  
Vol 72 (3) ◽  
pp. 828-835 ◽  
Author(s):  
C. M. Lucas ◽  
M. G. Havenith ◽  
F. H. van der Veen ◽  
J. Habets ◽  
T. van der Nagel ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Lactate Dehydrogenase ◽  
Latissimus Dorsi ◽  
Striated Muscle ◽  
Fiber Type ◽  
Large Animal ◽  
Type I ◽  
Force Frequency ◽  
Burst Frequency

To study functional, structural, and biochemical adaptations to electrical stimulation of striated muscle in a large animal, the canine latissimus dorsi (LD) muscle was conditioned continuously for 24 wk with an increasing number of pulse bursts (burst duration 250 ms, burst frequency 30 Hz). Force measurements in vivo after 12 wk showed a significant decrease in the ripple, the ratio of interstimulus to peak force amplitude, from 0.94 +/- 0.03 to 0.13 +/- 0.08 (SE; n = 8, P less than 0.05), indicating reduction in contractile speed. Also the steep part of the force-frequency relation shifted to lower frequencies. A significant change in fiber-type composition was seen with both enzyme- and immunohistochemistry, manifested by an increase of type I fibers from 29.5 +/- 2.9 to 83 +/- 8% (SE; n = 8, P less than 0.05). During this period a transient rise in the number of type IIc/Ic fibers (from 3 to 10%) was seen. In the stimulated muscle, capillary-to-fiber ratio increased from 1.9 +/- 0.4 to 2.7 +/- 0.1 (P less than 0.05). A significant increase in mitochondrial volume was also seen, especially in the peripheral part of the fiber. Both creatine kinase and lactate dehydrogenase revealed a significant decline in activity within 12 wk. At the same time a shift in lactate dehydrogenase-isozyme pattern was observed toward the cardiac composition. No additional changes occurred after 12 wk of stimulation, indicating that conversion of the canine LD muscle was complete within this period.

scholarly journals Multi-stable dynamics of the non-adiabatic repressilator

2015 ◽  
Vol 12 (104) ◽  
pp. 20141315 ◽  
Author(s):  
Ilya Potapov ◽  
Boris Zhurov ◽  
Evgeny Volkov
Keyword(s):  
Steady State ◽  
Intrinsic Noise ◽  
Stochastic Simulations ◽  
Stable Steady State ◽  
Genetic Circuits ◽  
The Times ◽  
Parameter Values ◽  
Considerable Range ◽  
Type Of Transition

The assumption of the fast binding of transcription factors (TFs) to promoters is a typical point in studies of synthetic genetic circuits functioning in bacteria. Although the assumption is effective for simplifying the models, it becomes questionable in the light of in vivo measurements of the times TF spends searching for its cognate DNA sites. We investigated the dynamics of the full idealized model of the paradigmatic genetic oscillator, the repressilator, using deterministic mathematical modelling and stochastic simulations. We found (using experimentally approved parameter values) that decreases in the TF binding rate changes the type of transition between steady state and oscillation. As a result, this gives rise to the hysteresis region in the parameter space, where both the steady state and the oscillation coexist. We further show that the hysteresis is persistent over a considerable range of the parameter values, but the presence of the oscillations is limited by the low rate of TF dimer degradation. Finally, the stochastic simulation of the model confirms the hysteresis with switching between the two attractors, resulting in highly skewed period distributions. Moreover, intrinsic noise stipulates trains of large-amplitude modulations around the stable steady state outside the hysteresis region, which makes the period distributions bimodal.

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