Calcium and Cardiac Rhythms

Bers, Donald M.

doi:10.1161/res.90.1.14

Cited by 134 publications

(27 citation statements)

References 28 publications

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“…To induce Ca 2ϩ overload acutely, we used a rat model of I͞R. I͞R of myocardium induces ventricular arrhythmias including ventricular premature beats, VT and VF in both experimental animal models and in man (9)(10)(11). Reperfusion of the ischemic myocardium results in an increase in intracellular Na ϩ and Ca 2ϩ (9)(10)(11).…”

Section: Discussionmentioning

confidence: 99%

“…This reduction in activity results in decreased SR Ca 2ϩ load and elevated diastolic Ca 2ϩ that induce after-depolarizations and triggered activity, culminating in ventricular arrhythmias (11). Triggered arrhythmias, including delayed after-depolarization (which occur when repolarization is completed and are mostly associated with cellular Ca 2ϩ overload), and early after-depolarizations [which are secondary depolarizations occurring before completion of the action-potential (AP) repolarization] are major initiators of VT and VF and, thus, fatal sudden events (11).…”

Section: Discussionmentioning

confidence: 99%

“…Under normal conditions, the excitation to contraction coupling is regulated by the sequential changes of ionic currents involved in the balance and timing of the membrane potential and the AP in the specialized pacemaker cells and in the myocytes (11). Imbalance of timing and activation of these heterogeneous contributors to pacemaker activity lead to arrhythmogenic events.…”

Section: Discussionmentioning

confidence: 99%

“…Imbalance of timing and activation of these heterogeneous contributors to pacemaker activity lead to arrhythmogenic events. K ϩ channel currents during the AP contribute to the repolarization phase by outward K ϩ currents (I to ), as well as the inward rectifier K ϩ current (I K1 ), which is meant to stabilize the membrane resting potential (E m ) (11). A reduction in K ϩ currents, as occur in failing hearts, leads to a more positive (depolarized) E m and to triggered activities (early after-depolarizations).…”

Section: Discussionmentioning

confidence: 99%

“…The failing myocytes also show a smaller Ca 2ϩ transients that may cause less complete inactivation of the inward Ca 2ϩ current (I Ca ) (physiological trigger of SR Ca 2ϩ release) during the early phases of the AP. Those factors combine to increase the likelihood of reactivation of inward I Ca and early after-depolarizations (11).…”

Section: Discussionmentioning

confidence: 99%

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Abrogation of ventricular arrhythmias in a model of ischemia and reperfusion by targeting myocardial calcium cycling

Monte

Lebeche

Guerrero

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

190

149

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Abnormal intracellular Ca 2؉ cycling plays an important role in cardiac dysfunction and ventricular arrhythmias in the setting of heart failure and transient cardiac ischemia followed by reperfusion (I͞R). We hypothesized that overexpression of the sarcoplasmic reticulum Ca 2؉ ATPase pump (SERCA2a) may improve both contractile dysfunction and ventricular arrhythmias. Continuous ECG recordings were obtained in 46 conscious rats after adenoviral gene transfer of either SERCA2a or the reporter gene ␤-galactosidase (␤gal) or parvalbumin (PV), as early as 48 h before and 48 h after 30 min ligation of the left anterior descending artery by using an implantable telemetry system. Sham-operated animals were used for comparison for hemodynamic measurements, whereas within-animal baseline was used for electrocardiographic and echocardiographic parameters. All episodes of nonsustained ventricular tachycardia (VT) and ventricular fibrillation (VF) were counted, and their durations were summed by telemetry. I͞R decreased regional cardiac wall thickening as well as the maximal rate of left ventricular pressure rise (؉dP͞dt) and ventricular pressure fall (؊dP͞dt). SERCA2a restored regional wall thickening and ؉dP͞dt and ؊dP͞dt to levels seen preoperatively. Regionalwall motion and anterior-wall thickening were improved in the SERCA2a animals, as assessed by echocardiography and piezoelectric crystals. To assess whether these effects are SERCA2a specific, we overexpressed a skeletal-muscle protein, PV, to examine whether Ca 2؉ buffering alone can mitigate ventricular arrhythmias. During the first hour after I͞R, the rate of nonsustained VT plus VF was 16 ؎ 5 episodes per h (n ‫؍‬ 6) in the Ad.␤gal group, 22 ؎ 6 in the Ad.PV group, and 4 ؎ 2 (n ‫؍‬ 6, P < 0.01) in the Ad.SERCA2a group. The decrease in VT plus VF in the Ad.SERCA2a group was consistent throughout the 48 h of monitoring. These results show that improving intracellular Ca 2؉ handling by overexpression of SERCA2a restores contractile function and reduces ventricular arrhythmias during I͞R.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Abrogation of ventricular arrhythmias in a model of ischemia and reperfusion by targeting myocardial calcium cycling

Monte

Lebeche

Guerrero

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

190

149

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Electrophysiological Substrates for Gender Difference in the Incidence of Torsades de Pointes Arrhythmias

et al. 2019

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How to Develop Bioresponsive MRI Probes Based on Paramagnetic Gd(III) for in vivo Applications

Yue

Angelovski

2023

Analysis & Sensing

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Among the many biological imaging techniques, magnetic resonance imaging (MRI) has been widely adopted for biomedical and clinical diagnostic applications, because of its ability to image deep tissues with high spatiotemporal resolution. Bioresponsive contrast agents are the key to expanding the diagnostic potential of MRI by providing anatomical information and discerning biochemical activity. Recent developments in the field of responsive and gadolinium‐based agents have resulted in novel complexes that can sense their chemical microenvironments and thus study various functional processes in the tissue. Herein, we discuss the design and use of Gd(III)‐based and bioresponsive MRI contrast agents for specific biological markers such as Ca(II) and Zn(II) cations and zwitterionic amino acid neurotransmitters. Combining their basic physicochemical characteristics with aspects that should be considered for their use in vivo would achieve the desired sensing features and enable their applications in functional molecular imaging to visualize essential biological processes.

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Calcium and Cardiac Rhythms

Cited by 134 publications

References 28 publications

Abrogation of ventricular arrhythmias in a model of ischemia and reperfusion by targeting myocardial calcium cycling

Abrogation of ventricular arrhythmias in a model of ischemia and reperfusion by targeting myocardial calcium cycling

Electrophysiological Substrates for Gender Difference in the Incidence of Torsades de Pointes Arrhythmias

How to Develop Bioresponsive MRI Probes Based on Paramagnetic Gd(III) for in vivo Applications

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