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General anesthetics protects against cardiac arrest-induced brain injury by inhibiting calcium wave propagation in zebrafish.

ABSTRACT: Cardiac arrest is a leading cause of death and disability worldwide. Although many victims are initially resuscitated, they often suffer from serious brain injury, even leading to a "persistent vegetative state". Therefore, it is need to explore therapies which restore and protect brain function after cardiac arrest. In the present study, using Tg (HuC:GCaMP5) zebrafish as a model, we found the zebrafish brain generated a burst of Ca2+ wave after cardiac arrest by in vivo time-lapse confocal imaging. The Ca2+ wave was firstly initiated at hindbrain and then sequentially propagated to midbrain and telencephalon, the neuron displayed Ca2+ overload after Ca2+ wave propagation. Consistent with this, our study further demonstrated neuronal apoptosis was increased in cardiac arrest zebrafish by TUNEL staining. The cardiac arrest-induced Ca2+ wave propagation can be prevented by general anesthetics such as midazolam or ketamine pretreatment. Moreover, midazolam or ketamine pretreatment dramatically decreased the neuronal apoptosis and improved the survival rate in CA zebrafish. Taken together, these findings provide the first in vivo evidence that general anesthetics pretreatment protects against cardiac arrest-induced brain injury by inhibiting calcium wave propagation in zebrafish.

SUBMITTER: Xu DJ

PROVIDER: S-EPMC5583756 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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General anesthetics protects against cardiac arrest-induced brain injury by inhibiting calcium wave propagation in zebrafish.

Xu Dao-Jie DJ Wang Bin B Zhao Xuan X Zheng Yi Y Du Jiu-Lin JL Wang Ying-Wei YW

Molecular brain 20170904 1

Cardiac arrest is a leading cause of death and disability worldwide. Although many victims are initially resuscitated, they often suffer from serious brain injury, even leading to a "persistent vegetative state". Therefore, it is need to explore therapies which restore and protect brain function after cardiac arrest. In the present study, using Tg (HuC:GCaMP5) zebrafish as a model, we found the zebrafish brain generated a burst of Ca<sup>2+</sup> wave after cardiac arrest by in vivo time-lapse c ...[more]

PMID: 28870222

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Project description:In normal atrial and ventricular tissue, the electrical wavefronts are mediated by the fast sodium current (I(Na)), whereas in sinoatrial and atrioventricular nodal tissue, conduction is mediated by the slow L-type calcium current (I(Ca,L)). However, it has not been shown whether the same tissue can exhibit both the I(Na)-mediated and the I(Ca,L)-mediated conduction.This study sought to test the hypothesis that bi-stable cardiac wave conduction, mediated by I(Na) and I(Ca,L), respectively, can occur in the same tissue under conditions promoting early afterdepolarizations (EADs), and to study how this novel wave dynamics is related to the mechanisms of EAD-mediated arrhythmias.Computer models of two-dimensional (2D) tissue with a physiologically detailed action potential model were used to study the bi-stable wave dynamics. Theoretical predictions were tested experimentally by optical mapping in neonatal rat ventricular myocyte monolayers.In the same 2D homogeneous tissue, we could induce spiral waves that are mediated by either I(Na) or I(Ca,L) under conditions in which the action potential model exhibited EADs. This bi-stable wave propagation behavior was similar to bi-stability shown in many other nonlinear systems. Because the bi-stable states are also excitable, we call this novel behavior bi-excitability. In a 2D heterogeneous tissue, the I(Ca,L)-mediated spiral wave meanders, giving rise to a twisting electrocardiographic QRS axis, resembling torsades de pointes, whereas the coexistence and interplay between the I(Na)-mediated wavefronts and I(Ca,L)-mediated wavefronts give rise to polymorphic ventricular tachycardia. We also present experimental evidence for bi-excitability under EAD-promoting conditions in neonatal rat ventricular myocyte monolayers exposed to BayK8644 and isoproterenol.Under EAD-prone conditions, both I(Na)-mediated conduction and I(Ca,L)-mediated conduction can occur in the same tissue. These novel wave dynamics may be responsible for certain EAD-mediated arrhythmias, such as torsades de pointes and polymorphic ventricular tachycardia.

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General anesthetics protects against cardiac arrest-induced brain injury by inhibiting calcium wave propagation in zebrafish.

Publications

General anesthetics protects against cardiac arrest-induced brain injury by inhibiting calcium wave propagation in zebrafish.

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