Cardiac mechano-electric coupling research: Fifty years of progress and scientific innovation

Quinn, T. Alexander; Kohl, Peter; Ravens, Ursula

doi:10.1016/j.pbiomolbio.2014.06.007

Cited by 63 publications

(36 citation statements)

References 77 publications

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“…). These effects have been implicated in the pro‐arrhythmogenesis of acute cardiac overload or ventricular dyssynchrony . It is not known whether JTV‐519 modifies the electrophysiological effects induced by acute myocardial stretch, and we hypothesize that these effects can be abolished by JTV‐519, taking account of its multichannel actions and attenuation of the Ca 2+ overload effects.…”

Section: Introductionmentioning

confidence: 94%

“…These effects have been implicated in the pro-arrhythmogenesis of acute cardiac overload or ventricular dyssynchrony. 24,25,[28][29][30][31] It is not known whether JTV-519 modifies the electrophysiological effects induced by acute myocardial stretch, and we hypothesize that these effects can be abolished by JTV-519, taking account of its multichannel actions and attenuation of the Ca 2+ overload effects. The present study uses an experimental model involving isolated Langendorff-perfused rabbit hearts to analyze the effects of JTV-519 upon the electrophysiological modifications produced by local acute ventricular mechanical stretch.…”

mentioning

confidence: 92%

“…3,12,13 Mechanical stretch induces an increase in cellular Na + inflow, activates the Na + /H + and reverse mode of the Na + /Ca 2+ exchangers [18][19][20][21][22] that leads to Ca 2+ overload, and modifies the cardiac electrophysiological properties, [23][24][25][26][27][28] favoring arrhythmia induction (mechanoelectric feedback). 24,[28][29][30][31] Acute myocardial stretching produces a shortening of the refractory periods, a decrease in the duration of the action potentials, a decrease in the wavelength (WL) of the activation process, depolarization of the resting potential, and the generation of after-depolarizations. [24][25][26][27][28] ).…”

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confidence: 99%

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Effects of JTV‐519 on stretch‐induced manifestations of mechanoelectric feedback

Canto¹,

Such-Miquel

Brines³

et al. 2016

Clin Exp Pharma Physio

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JTV-519 is a 1,4-benzothiazepine derivative with multichannel effects that inhibits Ca release from the sarcoplasmic reticulum and stabilizes the closed state of the ryanodine receptor, preventing myocardial damage and the induction of arrhythmias during Ca overload. Mechanical stretch increases cellular Na inflow, activates the reverse mode of the Na /Ca exchanger, and modifies Ca handling and myocardial electrophysiology, favoring arrhythmogenesis. This study aims to determine whether JTV-519 modifies the stretch-induced manifestations of mechanoelectric feedback. The ventricular fibrillation (VF) modifications induced by acute stretch were studied in Langendorff-perfused rabbit hearts using epicardial multiple electrodes under control conditions (n=9) or during JTV-519 perfusion: 0.1 μmol/L (n=9) and 1 μmol/L (n=9). Spectral and mapping techniques were used to establish the baseline, stretch and post-stretch VF characteristics. JTV-519 slowed baseline VF and decreased activation complexity. These effects were dose-dependent (baseline VF dominant frequency: control=13.9±2.2 Hz; JTV 0.1 μmol/L=11.1±1.1 Hz, P<.01; JTV 1 μmol/L=6.6±1.1 Hz, P<.0001). The stretch-induced acceleration of VF (control=38.8%) was significantly reduced by JTV-519 0.1 μmol/L (19.8%) and abolished by JTV 1 μmol/L (-1.5%). During stretch, the VF activation complexity index was reduced in both JTV-519 series (control=1.60±0.15; JTV 0.1 μmol/L=1.13±0.3, P<.0001; JTV 1 μmol/L=0.57±0.21, P<.0001), and was independently related to VF dominant frequency (R=.82; P<.0001). The fifth percentile of the VF activation intervals, conduction velocity and wavelength entered the multiple linear regression model using dominant frequency as the dependent variable (R=-.84; P<.0001). In conclusion, JTV-519 slowed and simplified the baseline VF activation patterns and abolished the stretch-induced manifestations of mechanoelectric feedback.

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Section: Introductionmentioning

confidence: 94%

mentioning

confidence: 92%

mentioning

confidence: 99%

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Effects of JTV‐519 on stretch‐induced manifestations of mechanoelectric feedback

Canto¹,

Such-Miquel

Brines³

et al. 2016

Clin Exp Pharma Physio

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“…This ‘mechano-electric feedback’ effect 12 was exploited by resuscitation pioneer Paul Zoll in the design of a mechanical pacing device for external stimulation of heart beats in emergency settings (‘cardiac thumper’) 13 . In dogs with normal sinus rhythm and high-degree atrioventricular block, repetitive heartbeats were evoked using this device, with no cases of mechanically-induced sustained arrhythmia (such as tachycardia or fibrillation, which can occur following VE M 14 ), even when stimulation occurred during the relative refractory period and at energies up to 10 times VE M threshold.…”

Section: Introductionmentioning

confidence: 99%

Comparing maximum rate and sustainability of pacing by mechanical vs. electrical stimulation in the Langendorff-perfused rabbit heart

Quinn

Kohl

2016

EP Europace

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AimsMechanical stimulation (MS) represents a readily available, non-invasive means of pacing the asystolic or bradycardic heart in patients, but benefits of MS at higher heart rates are unclear. Our aim was to assess the maximum rate and sustainability of excitation by MS vs. electrical stimulation (ES) in the isolated heart under normal physiological conditions.Methods and resultsTrains of local MS or ES at rates exceeding intrinsic sinus rhythm (overdrive pacing; lowest pacing rates 2.5±0.5 Hz) were applied to the same mid-left ventricular free-wall site on the epicardium of Langendorff-perfused rabbit hearts. Stimulation rates were progressively increased, with a recovery period of normal sinus rhythm between each stimulation period. Trains of MS caused repeated focal ventricular excitation from the site of stimulation. The maximum rate at which MS achieved 1:1 capture was lower than during ES (4.2±0.2 vs. 5.9±0.2 Hz, respectively). At all overdrive pacing rates for which repetitive MS was possible, 1:1 capture was reversibly lost after a finite number of cycles, even though same-site capture by ES remained possible. The number of MS cycles until loss of capture decreased with rising stimulation rate. If interspersed with ES, the number of MS to failure of capture was lower than for MS only.ConclusionIn this study, we demonstrate that the maximum pacing rate at which MS can be sustained is lower than that for same-site ES in isolated heart, and that, in contrast to ES, the sustainability of successful 1:1 capture by MS is limited. The mechanism(s) of differences in MS vs. ES pacing ability, potentially important for emergency heart rhythm management, are currently unknown, thus warranting further investigation.

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“…Other terms recognize the behavior’s underlying dependence on a contractility, such as “slow inotropic response” or “inotropic response to mechanical stretch”. Still another group of studies describes how altering load impacts action potential duration and arrhythmia – behavior termed contraction-excitation 4 or mechano-electric 5 coupling, and often associated with stretch-activated channels (SACs) 6, 7 . SACs include members of the transient receptor potential channel superfamily 8 and piezo 9 , and many of these channels are now thought to be involved with the SSC ( aka SFR).…”

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confidence: 99%

Response to Letter from Villa-Abrille et al

Kass

Seo

Rainer

2015

Circulation Research

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Cardiac mechano-electric coupling research: Fifty years of progress and scientific innovation

Cited by 63 publications

References 77 publications

Effects of JTV‐519 on stretch‐induced manifestations of mechanoelectric feedback

Effects of JTV‐519 on stretch‐induced manifestations of mechanoelectric feedback

Comparing maximum rate and sustainability of pacing by mechanical vs. electrical stimulation in the Langendorff-perfused rabbit heart

Response to Letter from Villa-Abrille et al

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