A new multi-scale simulation model of the circulation: from cells to system

Shim, Eun Bo; Leem, Chae Hun; Abe, Yasuyuki; Noma, Akinori

doi:10.1098/rsta.2006.1782

Cited by 25 publications

(24 citation statements)

References 22 publications

(31 reference statements)

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“…Their results are basically similar to ours, however, the increase in [Ca 2＋ ]i looks smaller with higher pacing frequency (Fig. 9 in Shim et al [60]). …”

supporting

confidence: 80%

“…Contradictory results among experiments in rat ventricular myocytes may arise from different level of ICaL depending on the experimental circumstances or individual variation among animals or myocytes. The relation between stimulation frequency and force or [Ca 2＋ ]i was also investigated by Shim et al [60] utilizing a new multi-scale simulation model. They proposed that [Ca 2＋ ]i has a positive relation with pacing frequency whereas left ventricular (LV) pressure has a negative one.…”

Section: Stimulation Frequency and Cytosolic Ca 2＋ Transientsmentioning

confidence: 99%

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A Computational Model of Cytosolic and Mitochondrial [Ca2+] in Paced Rat Ventricular Myocytes

Youm

Choi

Jang

et al. 2011

Korean J Physiol Pharmacol

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INTRODUCTIONThe major role of ventricular myocardium is to contract regularly in response to electrical excitation in order to pump oxygenated blood out of ventricle. Two key elements are directly involved in the normal cycle of contractile activity in ventricular myocytes. One is intracellular Ca 2＋ -cycling and the other is ATP synthesis by mitochondria. Upon release from sarcoplasmic reticulum (SR), Ca 2＋ binds to troponin C to move the tropomyosin away exposing the myosin-binding site of actin filament. If ATP and Ca 2＋ are high enough near the contractile apparatus, the cross bridge cycle continues and muscle would contract. In the end of contraction, majority of Ca 2＋ is pumped back into the Ca 2＋ store by SR Ca 2＋ pump then muscle relaxes.Therefore, disruption of either Ca 2＋-cycling or ATP synthesis can disturb normal cycle of ventricular contraction. ATP synthesis by mitochondria can directly or indirectly affect the Ca 2＋ -cycling by regulating the ATP-driven SR Ca 2＋ pump [1,2] and sarcolemmal Na ＋ /K ＋ pump [1].Metabolic inhibitors are supposed to suppress the normal cycle of contraction via this mechanism. There has been evidence that Ca 2＋-cycling affects the ATP synthesis in mitochondria. Increased mitochondrial Ca 2＋ influx across the inner mitochondrial membrane has been known to stimulate F0F1-ATPase activity [3,4]. Increase in mitochondrial [Ca 2＋ ] ([Ca 2＋ ]m) has also been known to stimulate tricarboxylic acid (TCA) cycle dehydrogenases [5,6]. The resultant increase in NADH could affect the ATP synthesis of mitochondria. This is supposed to be the control mechanism that matches energy demand for bigger contraction induced by higher cytosolic (or intracellular) [Ca 2＋ ] ( [Ca 2＋ ]i) [7]. There is a controversial issue on the possibility that [Ca 2＋ ]m changes in a beat-to-beat manner. Beat-to-beat mitochondrial Ca 2＋ transients have been identified on adult 218JB Youm, et al rabbit cardiac myocytes [8] and on rat cardiac myocytes [9]. In contrast, beat-to-beat change in [Ca 2＋ ]m was not identified on cat ventricular myocytes [10]. Further complicating thing is that the ATP depletion can affect action potential (AP) waveform by stimulating ATP sensitive K ＋ channel.Reduced action potential duration (APD) by activation of ATP sensitive K ＋ channel can reduce the energy demand during contraction. All above observations demonstrate how complex the interaction among Ca 2＋-cycling, ATP production, and electrical excitation could be. If all those elements are properly modeled, an integrated mathematical model could be developed and utilized to investigate those complex interactions.Recently, cardiac models integrating electrophysiology, Ca 2＋ cycling, and energy metabolism have emerged based on experimental results from guinea pig ventricular myocytes [11,12]. Although they were able to couple mitochondrial energetics to excitation-contraction coupling, the description of mitochondrial ion transport is limited and the modeling of pHm and pHi is lacking which is a key elem...

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“…Their results are basically similar to ours, however, the increase in [Ca 2＋ ]i looks smaller with higher pacing frequency (Fig. 9 in Shim et al [60]). …”

supporting

confidence: 80%

Section: Stimulation Frequency and Cytosolic Ca 2＋ Transientsmentioning

confidence: 99%

A Computational Model of Cytosolic and Mitochondrial [Ca2+] in Paced Rat Ventricular Myocytes

Youm

Choi

Jang

et al. 2011

Korean J Physiol Pharmacol

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“…Multiscale computational approaches have been employed in understanding various aspects of the circulatory system from the mechanical properties of the heart muscle due to aging and plaque to cardiovascular circulatory mechanics [Shim et al 2006]. We expect that continuum based computations will be of use in coupling the dynamical characteristics of the circulation to the activation-induced mechanical contraction of the heart muscle.…”

Section: Multiscale Approaches: From Cell Mechanics To Collective Tismentioning

confidence: 99%

Continuum-based computational models for cell and nuclear mechanics

Vaziri

Gopinath

Deshpande

2007

JOMMS

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Deciphering the relationship between cellular processes and the structure of living cells is a key step toward understanding and predicting cell functions with direct implications for understanding human health and disease. The active nature of these cellular processes, which span several decades of spatial and temporal scales, pose significant challenges to unraveling this complex structure-function paradigm.Complementing novel experimental techniques with robust computational approaches capable of modeling mechanical response at varying scales provides new avenues to resolving this paradigm. We provide an overview of continuum-based computational approaches used in studying and interpreting responses of individual cells and nuclei, we outline techniques used for measuring the mechanical characteristics of living cells, and we discuss some of the key insights provided by these approaches.

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“…The circulatory system model of the Japanese authors Shim et al (Shim et al 2006) can be given as an example of connecting models of various hierarchical levels; these authors combined a simple model of cardiovascular haemodynamics of the vascular system with the model of ventricles of the heart (Fig. 5), acting as a heart pump.…”

Section: System Research Must Include (Peter Kohl and Noble 2009)mentioning

confidence: 99%

“…For example, this path was taken by the international research team of the SAPHIR (System Approach for Physiological Integration of Renal, cardiac and respiratory control) project in 2008 after deciding that Figure 5. The integrative model of the cardiovascular system as a combination of models on various hierarchical levels according to (Shim et al 2006). Hester, Coleman, and Summers 2008) at that time seemed very poorly readable and diffi cult to understand to the project participants.…”

Section: Hummodmentioning

confidence: 99%

Integrative physiology in Modelica

Kofránek¹,

Kulhánek²,

Matejak³

et al. 2017

Linköping Electronic Conference Proceedings

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The integrative model of human physiology connects individual physiological subsystems into a single unit. They are enormous (contain thousands of variables) and represent a formalized description of interconnected physiological regulations. The issue of formalization of physiological systems became part of a series of international projects (e.g. the worldwide program "PHYSIOME", or the European program "VIRTUAL PHYSIOLOGICAL HUMAN"). The development of large-scale models of human physiology was facilitated by a new generation (i.e. equation-based) of simulation environments, especially by the Modelica language. These models can be used to explain the causal relations of the pathogenesis of many diseases. They can be applied in the evaluation of clinical trials and they can also be used in the core of sophisticated medical simulators.

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A new multi-scale simulation model of the circulation: from cells to system

Cited by 25 publications

References 22 publications

A Computational Model of Cytosolic and Mitochondrial [Ca2+] in Paced Rat Ventricular Myocytes

A Computational Model of Cytosolic and Mitochondrial [Ca2+] in Paced Rat Ventricular Myocytes

Continuum-based computational models for cell and nuclear mechanics

Integrative physiology in Modelica

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