Experimental Studies on Myocardial Stretch and Ventricular Arrhythmia in Hypertrophied and Non-Hypertrophied Hearts

Evans, Stephen; DALTON, G; Levi, Allan J.

doi:10.1177/204748730000700302

Cited by 8 publications

(4 citation statements)

References 56 publications

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“…In addition to autonomic responses, this temporal pattern can be attributed to differences in the substrate, created by ischemia versus evolving MI ( 1 , 25 ). Furthermore, LV-afterload reduction [often observed as a delayed effect after clonidine administration ( 38 )] may have contributed to this pattern, by decreasing wall-stress and, thereby, stretch-induced VT/VF ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Central Sympathetic Activation and Arrhythmogenesis during Acute Myocardial Infarction: Modulating Effects of Endothelin-B Receptors

Kolettis

Kontonika

Barka

et al. 2015

Front. Cardiovasc. Med.

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Sympathetic activation during acute myocardial infarction (MI) is an important arrhythmogenic mechanism, but the role of central autonomic inputs and their modulating factors remain unclear. Using the in vivo rat-model, we examined the effects of clonidine, a centrally acting sympatholytic agent, in the presence or absence of myocardial endothelin-B (ETB) receptors. We studied wild-type (n = 20) and ETB-deficient rats (n = 20) after permanent coronary ligation, with or without pretreatment with clonidine. Cardiac rhythm was continuously recorded for 24 h by implantable telemetry devices, coupled by the assessment of autonomic and heart failure indices. Sympathetic activation and arrhythmogenesis were more prominent in ETB-deficient rats during the early phase post-ligation. Clonidine improved these outcomes throughout the observation period in ETB-deficient rats, but only during the delayed phase in wild-type rats. However, this benefit was counterbalanced by atrioventricular conduction abnormalities and by higher incidence of heart failure, the latter particularly evident in ETB-deficient rats. Myocardial ETB-receptors attenuate the arrhythmogenic effects of central sympathetic activation during acute MI. ETB-receptor deficiency potentiates the sympatholytic effects of clonidine and aggravates heart failure. The interaction between endothelin and sympathetic responses during myocardial ischemia/infarction and its impact on arrhythmogenesis and left ventricular dysfunction merits further investigation.

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Section: Discussionmentioning

confidence: 99%

Central Sympathetic Activation and Arrhythmogenesis during Acute Myocardial Infarction: Modulating Effects of Endothelin-B Receptors

Kolettis

Kontonika

Barka

et al. 2015

Front. Cardiovasc. Med.

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“…The role that this plays in healthy heart is unclear, but we hypothesised that an exaggeration of this response in hypertrophic hearts may explain the high risk of SCD in patients with hypertrophy and early failure. The hypertrophied heart indeed shows increased sensitivity to stretch-induced arrhythmias2 and increased stretch-activated currents in myocytes from hypertrophied animal and human hearts has been directly demonstrated 3. We have now extended these observations by examining stretch-induced ectopic beats in isolated hearts from Wistar-Kyoto (control) and SHR 4.…”

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confidence: 66%

18 Mechanically induced arrhythmias: a neglected target?

Saint

2010

Heart

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domains, phase singularities that locate the organisation centres of re-entrant waves at the surface. Such spatial maps allow putative mechanisms for arrhythmias to be tested, for example, the mother rotor hypothesis for fibrillation. We present spatial maps we have obtained of APD, repolarisation time, discordant alternans, dominant frequencies and phase singularities during fibrillation obtained from optical imaging experiments (mouse, rat, guinea pig, rabbit and pig) and simulations (mouse, rat, rabbit, dog, human) and quantify the maps and their dynamics.It is known that stretch of the ventricles is arrhythmogenic. 1 The role that this plays in healthy heart is unclear, but we hypothesised that an exaggeration of this response in hypertrophic hearts may explain the high risk of SCD in patients with hypertrophy and early failure. The hypertrophied heart indeed shows increased sensitivity to stretch-induced arrhythmias 2 and increased stretch-activated currents in myocytes from hypertrophied animal and human hearts has been directly demonstrated. 3 We have now extended these observations by examining stretch-induced ectopic beats in isolated hearts from Wistar-Kyoto (control) and SHR. 4 Our results show that hypertrophic hearts are more sensitive to mechanically induced arrhythmias and that the putative stretch-activated channel blocker streptomycin reduces this sensitivity. Hearts from SHR had a threshold for stretch-induced ectopic beats of 21.263.6 mm Hg (n¼5) compared to 49.464.7 mm Hg in Wistar Kyoto (n¼5), p<0.01). Perfusion of the hearts with 100 mM streptomycin increased the threshold in both (to 39.769.0 mm Hg in SHR (n¼5); p¼0.07 vs 69.466.9 mm Hg in control (n¼5); p¼0.04). These data add to growing evidence that mechanical effects on the myocardium may contribute to arrhythmias in many clinical situations and suggest that efforts at developing anti-arrhythmic agents with this as a target may prove fruitful. 5 As yet there is no guidance for the study of such arrhythmias and provision for this is required in the Lambeth Conventions update. REFERENCES 1. Zabel M, Koller BS, Sachs F, et al.The hERG gene encodes a potassium channel responsible for the repolarisation of the IKr current in cardiac cells. Given the importance of this channel in the repolarisation of the cardiac action potential, and the disturbances of channel function by certain compounds such as anti-arrhythmias and anti-psychotics, this channel has become very important in safety pharmacology testing. Since some hERG-active compounds also exhibit different pharmacology at physiological temperature, experiments performed at this temperature are important in yielding more relevant data in safety screening. In this study, we describe the use of automated patch clamp electrophysiology for recording hERG stably transfected in HEK293 cells. Recordings of the hERG current from up to eight cells simultaneously could be performed at room temperature (RT) and at physiological temperature. Data will be shown for erythromycin which exhibited a highe...

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“…Cheng et al (1995) found an increase in programmed cell death in response to myocardial distension [51]. In this case, stretching of the myocardium can occur both in physiological conditions (for example, heavy physical exertion) and in several pathological conditions (for example, in heart failure and arterial hypertension), which possibly contributes to an increase in the level of troponins [52][53][54]. Singh et al (2001) investigated the effect of enhanced neurohumoral stimulation on apoptosis processes and found that stimulation of beta1-adrenergic receptors induces apoptosis via activation of adenylyl cyclase [55], while stimulation of beta2-adrenergic receptors, on the contrary, has an antiapoptotic effect [56,57].…”

Section: The Role Of Apoptosis In the Release Of Troponins From Cardiomyocytesmentioning

confidence: 99%

Cardiac Troponins Metabolism: From Biochemical Mechanisms to Clinical Practice (Literature Review)

Chaulin

2021

IJMS

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The metabolic processes of endo- and exogenous compounds play an important role in diagnosing and treating patients since many metabolites are laboratory biomarkers and/or targets for therapeutic agents. Cardiac troponins are one of the most critical biomarkers to diagnose cardiovascular diseases, including acute myocardial infarction. The study of troponin metabolism is of great interest as it opens up new possibilities for optimizing laboratory diagnostics. This article discusses in detail the key stages of the cardiac troponins metabolism, in particular the mechanisms of release from a healthy myocardium, mechanisms of circulation in the bloodstream, possible mechanisms of troponin penetration into other biological fluids (oral fluid, cerebrospinal fluid, pericardial and amniotic fluids), mechanisms of elimination of cardiac troponins from the blood, and daily changes in the levels of troponins in the blood. Considering these aspects of cardiac troponin metabolism, attention is focused on the potential value for clinical practice.

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Experimental Studies on Myocardial Stretch and Ventricular Arrhythmia in Hypertrophied and Non-Hypertrophied Hearts

Cited by 8 publications

References 56 publications

Central Sympathetic Activation and Arrhythmogenesis during Acute Myocardial Infarction: Modulating Effects of Endothelin-B Receptors

Central Sympathetic Activation and Arrhythmogenesis during Acute Myocardial Infarction: Modulating Effects of Endothelin-B Receptors

18 Mechanically induced arrhythmias: a neglected target?

Cardiac Troponins Metabolism: From Biochemical Mechanisms to Clinical Practice (Literature Review)

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