Suppression of Ventricular Arrhythmias During Ischemia-Reperfusion by Agents Inhibiting Ins(1,4,5)P
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Du, Xiao‐Jun; Anderson, Karen E.; Jacobsen, Alexander; Woodcock, Elizabeth A.; Dart, Anthony M.

doi:10.1161/01.cir.91.11.2712

Cited by 75 publications

(62 citation statements)

References 27 publications

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“…[145,172,173]. Inhibition of the Na + /H + exchanger (NHE) and NCX is also effective against the development of the arrhythmias [174,175].…”

Section: Atrial Fibrillationmentioning

confidence: 99%

“…The increase in IP 3 concentration correlates with the induction of arrhythmias, ventricular tachycardia and ventricular fibrillation [145]. Substances able to inhibit the IP 3 increase prevent the arrhythmias [145,172,173]. Inhibition of the Na + /H + exchanger (NHE) and NCX is also effective against the development of the arrhythmias [174,175].…”

Section: Reperfusion Arrhythmiasmentioning

confidence: 99%

See 1 more Smart Citation

Emerging roles of inositol 1,4,5-trisphosphate signaling in cardiac myocytes

Kockskämper

Zima

Roderick

et al. 2008

Journal of Molecular and Cellular Cardiology

173

149

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Inositol 1,4,5-trisphosphate (IP 3 ) is a ubiquitous intracellular messenger regulating diverse functions in almost all mammalian cell types. It is generated by membrane receptors that couple to phospholipase C (PLC), an enzyme which liberates IP 3 from phosphatidylinositol 4,5-bisphosphate (PIP 2 ). The major action of IP 3 , which is hydrophilic and thus translocates from the membrane into the cytoplasm, is to induce Ca 2+ release from endogenous stores through IP 3 receptors (IP 3 Rs). Cardiac excitation-contraction coupling relies largely on ryanodine receptor (RyR)-induced Ca 2+ release from the sarcoplasmic reticulum. Myocytes express a significantly larger number of RyRs compared to IP 3 Rs (∼100:1), and furthermore they experience substantial fluxes of Ca 2+ with each heartbeat. Therefore, the role of IP 3 and IP 3 -mediated Ca 2+ signaling in cardiac myocytes has long been enigmatic. Recent evidence, however, indicates that despite their paucity cardiac IP 3 Rs may play crucial roles in regulating diverse cardiac functions. Strategic localization of IP 3 Rs in cytoplasmic compartments and the nucleus enables them to participate in subsarcolemmal, bulk cytoplasmic and nuclear Ca 2+ signaling in embryonic stem cell-derived and neonatal cardiomyocytes, and in adult cardiac myocytes from the atria and ventricles. Intriguingly, expression of both IP 3 Rs and membrane receptors that couple to PLC/IP 3 signaling is altered in cardiac disease such as atrial fibrillation or heart failure, suggesting the involvement of IP 3 signaling in the pathology of these diseases. Thus, IP 3 exerts important physiological and pathological functions in the heart, ranging from the regulation of pacemaking, excitation-contraction and excitation-transcription coupling to the initiation and/or progression of arrhythmias, hypertrophy and heart failure. KeywordsInositol 1,4,5-trisphosphate; Cardiac myocyte; Calcium; Inotropy; Arrhythmias; Nucleus; Hypertrophy © 2008 Elsevier Inc. All rights reserved. * Corresponding author. E-mail address: jens.kockskaemper@meduni-graz.at (J. Kockskämper).. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript The discovery of IP 3A quarter of a century ago it was shown that D-myo inositol 1,4,5-trisphosphate (IP 3 ) releases Ca 2+ from a non-mitochondrial internal Ca 2+ store [1]. Since this hallmark discovery, IP 3 has emerged as a ubiquitous intracellular messenger, releasing Ca 2+ from stores through activation of IP 3 receptors (IP 3 Rs) in almost all eukaryotic cells. The major IP 3 -sensitive intracellular Ca 2+ store is the endoplasmic reticulum. However, IP 3 has also been shown to release Ca 2+ stored in other compartments, such as the Golgi and the nuclear envelope [2]. In addition, IP 3 Rs are present on the plasma membrane of some cell types, where they can gate Ca 2+ influx [3]. A crucial role for IP 3 -dependent Ca 2+ release has been demonstrated in many mammalian cell types, ranging from tiny platelets, where it initiates blood clottin...

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“…[145,172,173]. Inhibition of the Na + /H + exchanger (NHE) and NCX is also effective against the development of the arrhythmias [174,175].…”

Section: Atrial Fibrillationmentioning

confidence: 99%

Section: Reperfusion Arrhythmiasmentioning

confidence: 99%

Emerging roles of inositol 1,4,5-trisphosphate signaling in cardiac myocytes

Kockskämper

Zima

Roderick

et al. 2008

Journal of Molecular and Cellular Cardiology

173

149

View full text Add to dashboard Cite

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“…Esses canais estão localizados no sarcolema e são regulados pela enzima translocadora Na/Ca e também pela liberação do Ca ++ pelo retículo sarcoplasmático 11,12 . Assim, com a perda do rigoroso controle sobre a coordenação dos mecanismos intracelulares, ocorrem as disritmias de reperfusão, cujo mecanismo está relacionado com as oscilações transitórias do Ca ++ citosólico e superestimulação do ciclo do ácido tricarboxílico 13,14 . Finalmente, em decorrência da sobrecarga de Ca ++ mitocondrial vai ocorrer explosão na geração de ROS.…”

Section: Lesão Celular Decorrente Da Isquemia E Reperfusãounclassified

“…Those channels are located in the sarcolema and they are regulated by the Na/Ca exchange protein and also by the release of Ca ++ from the sarcoplasmatic reticulum 11,12 . Therefore, the loss of the rigid control on coordination of intracellular mechanisms lead to the development of reperfusion arrhythmias, whose mechanism is related with the transient oscillation of cytosolic Ca ++ and hyperstimulation of the tricarboxylic acid cycle 13,14 . Finally, due to the mitochondrial overload of Ca ++ , the generation of ROS increases dramatically.…”

Section: Cell Damage Secondary To Ischemia and Reperfusionmentioning

confidence: 99%

Proteção miocárdica pelo pré- e pós-condicionamento anestésico

Pasqualin¹,

Auler²

2008

Rev. Bras. Anestesiol.

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JUSTIFICATIVA E OBJETIVO:A isquemia miocárdica perioperatória é um evento comumente observado no período perioperatório podendo aumentar significativamente a morbimortalidade pós-cirúrgica. As propriedades cardioprotetoras dos anestésicos voláteis e dos opióides têm sido estudadas durante algumas décadas e hoje constituem poderosas ferramentas no manuseio de pacientes com doença coronariana isquêmica. O objetivo desta revisão foi fornecer fundamentos da proteção miocárdica por precondicionamento. CONTEÚDO:Serão discutidos os conceitos sobre lesão celular decorrente de isquemia e reperfusão, precondicionamento isquê-mico (PCI), precondicionamento anestésico (PCA), assim como os mecanismos de proteção miocárdica. Estudos recentes em cirurgia cardíaca demonstram que a aplicação de curtos períodos de isquemia, durante a reperfusão, podem reduzir a área de infarto do miocárdio. Os anestésicos voláteis também podem apresentar efeito protetor na reperfusão miocárdica. Independentemente da via de sinalização que leva ao precondicionamento, tanto aqueles que envolvem anestésicos quanto o isquêmico, considera-se que os canais de KATP dependentes mitocondriais sejam os mediadores finais de cardioproteção por controlarem o influxo de cálcio na mitocôndria e prevenirem a indução da necrose e apoptose. Apesar do PCI e PCA efetivamente reduzirem a área de infarto do miocárdio e melhorarem a função ventricular pós-operatória, é importante salientar que esses tratamentos devem ser anteriores ao evento isquêmics no sentido de justificar sua aplicabilidade clínica. CONCLUSÕES:Os fenômenos conhecidos como precondicionamento isquêmico e precondicionamento anestésico do miocárdi, são bem conhecidos, sendo o mecanismo de proteção similar em ambas as situações, porém nem todos os passos que levam a esta proteção foram completamente esclarecidos. Mais investigações são necessária, para que as propriedades cardioprotetoras dos agentes anestésicos possam ter aplicabilidade clínica crescente.

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“…Such a mechanism might serve to reduce the generation of Ins(1,4,5)P 3 because that is potentially arrhythmogenic (12,(15)(16)(17). However, it is also possible that products of these Ins(1,4)P 2 -generating pathways have a functional significance of their own.…”

mentioning

confidence: 99%