Isolated heart models for studying cardiac electrophysiology: a historical perspective and recent advances

Yeo, Jie Ming; Tse, Vivian; Kung, Judy; Lin, Hiu Yu; Lee, Yee Ting; Kwan, Joseph; Yan, Bryan P.; Tse, Gary

doi:10.1515/jbcpp-2016-0110

Cited by 17 publications

(11 citation statements)

References 109 publications

(107 reference statements)

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“…Our results show that MI injury causes the peak current density of the I Na to increase, leading to the increase in the amplitude of the AP. The major component of the delayed rectifier potassium channel current is the KCNQ2/KCNQ3 (Kv7.2/Kv7.3) subunits ( Shapiro et al, 2000 ; Matsumoto et al, 2010 ), and is one of the major currents in the AP repolarization course ( Zhang et al, 2018 ) and directly affects the AP repolarization time ( Yeo et al, 2017 ). Our results show that MI leads to an increase of the peak current density of the delayed rectifier potassium channel current.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Ion Channels in the Superior Cervical Ganglion Neurons by Myocardial Ischemia and Fluvastatin Treatment

et al. 2018

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Background: The superior cervical ganglion (SCG) of the autonomic nervous system plays an important role in different cardiovascular diseases. In this study, we investigated the effects of ischemia and fluvastatin treatment on the ion channel characteristics of SCG neurons in a rabbit myocardial ischemia (MI) model.Methods: MI was induced by abdominal subcutaneous injections of isoproterenol (ISO). The properties of the delayed rectifier potassium channel current (IK), sodium channel current (INa), and action potential (APs) on isolated SCG neurons in the control, MI-7d, MI-14d, fluvastatin-7d (fluvastatin pretreated 14 days and treated 7 days after ISO-induced MI), and fluvastatin-14d (fluvastatin pretreated 14 days and treated 14 days after ISO-induced MI) groups were studied. In addition, the RNA expressions of KCNQ3 and SCN9A in the SCG tissue were determined by performing real-time PCR. Intracellular calcium concentration was monitored using laser scanning confocal microscopy.Results: Compared with the control group, the current amplitude of IK and INa were increased in the MI-7d and MI-14d groups. KCNQ3 RNA (corresponding to channel proteins of IK) expression and SCN9A RNA (corresponding to channel proteins of INa) expression were also increased in MI groups. Activation and inactivation curves for INa in the two MI groups shifted negatively compared with the control group. These changes were reversed by fluvastatin treatment. Intracellular calcium concentration in SCG neurons was not altered significantly by MI or fluvastatin treatment. By contrast, increased AP amplitude and shortened APD90 were observed in the MI-7d and MI-14d groups. These changes were reversed in the fluvastatin-treated MI group.Conclusion: Fluvastatin treatment partly reversed the characteristics of SCG neurons in MI. The ion channel of SCG neurons could be one of the potential targets of fluvastatin in treating coronary heart diseases.

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Section: Discussionmentioning

confidence: 99%

Modulation of Ion Channels in the Superior Cervical Ganglion Neurons by Myocardial Ischemia and Fluvastatin Treatment

et al. 2018

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“…Of the different animal models, mouse hearts have been a popular system for investigating cardiac electrophysiology owing to their ease of reproduction, access, genetic and pharmacological manipulation [ 26 , 27 ]. For example, the effects of loss of the gap junction protein, connexin 43, have been studied in great detail [ 13 , 22 , 28 – 36 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of pharmacological gap junction and sodium channel blockade on S1S2 restitution properties in Langendorff-perfused mouse hearts

Tse

Liu

et al. 2017

Oncotarget

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Gap junctions and sodium channels are the major molecular determinants of normal and abnormal electrical conduction through the myocardium, however, their exact contributions to arrhythmogenesis are unclear. We examined conduction and recovery properties of regular (S1) and extrasystolic (S2) action potentials (APs), S1S2 restitution and ventricular arrhythmogenicity using the gap junction and sodium channel inhibitor heptanol (2 mM) in Langendorff-perfused mouse hearts (n=10). Monophasic action potential recordings obtained during S1S2 pacing showed that heptanol increased the proportion of hearts showing inducible ventricular tachycardia (0/10 vs. 5/8 hearts (Fisher’s exact test, P < 0.05), prolonged activation latencies of S1 and S2 APs, thereby decreasing S2/S1 activation latency ratio (ANOVA, P < 0.05) despite prolonged ventricular effective refractory period (VERP). It did not alter S1 action potential duration at 90% repolarization (APD90) but prolonged S2 APD90 (P < 0.05), thereby increasing S2/S1 APD90 ratio (P < 0.05). It did not alter maximum conduction velocity (CV) restitution gradient or maximum CV reductions but decreased the restitution time constant (P < 0.05). It increased maximal APD90 restitution gradient (P < 0.05) without altering critical diastolic interval or maximum APD90 reductions. Pro-arrhythmic effects of 2 mM heptanol are explicable by delayed conduction and abnormal electrical restitution. We concluded that gap junctions modulated via heptanol (0.05 mM) increased arrhythmogenicity through a delay in conduction, while sodium channel inhibition by a higher concentration of heptanol (2 mM) increased arrhythmogenicity via additional mechanisms, such as abnormalities in APDs and CV restitution.

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“…The perfusion solution flows through the coronary circulation and reaches the right atrium via the coronary sinus. As perfusion starts, the heart recovers its own automaticity and beats spontaneously for many hours (as reviewed in [ 14 ]).…”

Section: Methodologies For the Decellularization Of The Heartmentioning

confidence: 99%

The Rapidly Evolving Concept of Whole Heart Engineering

Iop

Sasso

Menabò

et al. 2017

Stem Cells International

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Whole heart engineering represents an incredible journey with as final destination the challenging aim to solve end-stage cardiac failure with a biocompatible and living organ equivalent. Its evolution started in 2008 with rodent organs and is nowadays moving closer to clinical application thanks to scaling-up strategies to human hearts. This review will offer a comprehensive examination on the important stages to be reached for the bioengineering of the whole heart, by describing the approaches of organ decellularization, repopulation, and maturation so far applied and the novel technologies of potential interest. In addition, it will carefully address important demands that still need to be satisfied in order to move to a real clinical translation of the whole bioengineering heart concept.

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Isolated heart models for studying cardiac electrophysiology: a historical perspective and recent advances

Cited by 17 publications

References 109 publications

Modulation of Ion Channels in the Superior Cervical Ganglion Neurons by Myocardial Ischemia and Fluvastatin Treatment

Modulation of Ion Channels in the Superior Cervical Ganglion Neurons by Myocardial Ischemia and Fluvastatin Treatment

Effects of pharmacological gap junction and sodium channel blockade on S1S2 restitution properties in Langendorff-perfused mouse hearts

The Rapidly Evolving Concept of Whole Heart Engineering

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