Protection of Cardiac Myocytes from Hypothermic Injury by Cardiac Fibroblasts Isolated from Neonatal Rat Ventricle

Orita, Hiroyuki; Fukasawa, Manabu; Hirooka, Shigeki; Fukui, Kana; Kohi, Minoru; M, Washio; Sasaki, Hideo

doi:10.1006/jsre.1993.1199

Cited by 17 publications

(4 citation statements)

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“…Similar to Kamkin and colleagues, the increase in fibroblast density correlated with the attenuation of spontaneous activity (Orita et al 1993;Kamkin et al 2003). The observed decrease in the conduction velocity was also comparable to the changes previously described for these conditions (Panfilov, 2002;Miragoli et al 2006).…”

Section: Depolarizing Influence Of Fibroblasts On Cardiomyocytessupporting

confidence: 89%

“…The percentage of fibroblasts is described to increase during ageing due to the loss of sinus nodal cells, which could be a potential contributor to ageing-induced bradycardia or sick sinus syndrome (Shiraishi et al 1992;de Marneffe et al 1995). This hypothesis is supported by in vitro experiments where intercellular coupling of neonatal cardiomyocytes with fibroblasts decreased the myocytes spontaneous beating frequency in cell pairs as well as in monolayers (Orita et al 1993;Kamkin et al 2002). This effect could be prevented by the use of fibroblasts deficient for the expression of Cx43 (Kizana et al 2006).…”

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confidence: 79%

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The relevance of non‐excitable cells for cardiac pacemaker function

Fahrenbach

Mejía-Alvarez

Banach

2007

The Journal of Physiology

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Age-dependent changes in the architecture of the sinus node comprise an increasing ratio between fibroblasts and cardiomyocytes. This change is discussed as a potential mechanism for sinus node disease. The goal of this study was to determine the mechanism through which non-excitable cells influence the spontaneous activity of multicellular cardiomyocyte preparations. Cardiomyocyte monolayers (HL-1 cells) or embryonic stem cell-derived cardiomyocytes were used as two-and three-dimensional cardiac pacemaker models. Spontaneous activity and conduction velocity (θ) were monitored by field potential measurements with microelectrode arrays (MEAs). The influence of fibroblasts (WT-fibs) was determined in heterocellular cultures of different cardiomyocyte and fibroblast ratios. The relevance of heterocellular gap junctional coupling was evaluated by the use of fibroblasts deficient for the expression of Cx43 (Cx43 −/− -fibs). The beating frequency and θ of heterocellular cultures depended negatively on the fibroblast concentration. Interspersion of fibroblasts in cardiomyocyte monolayers increased the coefficient of the interbeat interval variability. Whereas Cx43−/− -fibs decreased θ significantly less than WT-fibs, their effect on the beating frequency and the beat-to-beat variability seemed largely independent of their ability to establish intercellular coupling. These results suggest that electrically integrated, non-excitable cells modulate the excitability of cardiac pacemaker preparations by two distinct mechanisms, one dependent and the other independent of the heterocellular coupling established. Whereas heterocellular coupling enables the fibroblast to depolarize the cardiomyocytes or to act as a current sink, the mere physical separation of the cardiomyocytes by fibroblasts induces bradycardia through a reduction in frequency entrainment.

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Section: Depolarizing Influence Of Fibroblasts On Cardiomyocytessupporting

confidence: 89%

mentioning

confidence: 79%

The relevance of non‐excitable cells for cardiac pacemaker function

Fahrenbach

Mejía-Alvarez

Banach

2007

The Journal of Physiology

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“…In particular, TNF-α, as a key inflammatory mediator, is reported to have a paradoxical effect including both protecting and detrimental roles in ischemia-induced heart dysfunction [30, 31]. Second, cardiac fibroblasts which constitutes the majority of non-myocyte cells in the heart, has been reported to prevent cardiac myocytes from hypothermic lesions by producing some grow factors and cytokines and interacting with other cell types [32]. Conversely, Kawaguchi et al indicated that inflammasome activation in myofibroblast contributes to the I/R injury [18].…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine-induced cardioprotection is mediated by inhibition of high mobility group box-1 and the cholinergic anti-inflammatory pathway in myocardial ischemia-reperfusion injury

et al. 2019

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Objectives Dexmedetomidine (DEX) is a selective α2-adrenoceptor agonist that has anti-inflammatory and cardioprotective effects in myocardial ischemia/reperfusion (I/R) injury. The present study aimed to investigate the underlying mechanism by which DEX protects against myocardial I/R. Methods Sprague Dawley rats were subjected to either sham operation or myocardial I/R, which was induced by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for 120 min. Rats were treated with either DEX or saline prior to surgery. We measured heart infarct size, serum cardiac Troponin I (cTnI), cardiac High mobility group box-1 (HMGB1) expression, myocardial apoptosis and cytokine production of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Besides, we evaluated the heart function at 4 weeks post-reperfusion by echocardiography. Unilateral vagotomy or inhibition of the α7 nicotinic acetylcholine receptor (α7nAChR) with methyllycaconitine (MLA) was applied to investigate whether DEX-induced cardioprotection is mediated via the cholinergic anti-inflammatory pathway. Cardiac-selective overexpression of HMGB1 was administered to further confirm if HMGB1 is a key anti-inflammatory target during DEX-induced cardioprotection. Results DEX pretreatment significantly attenuated I/R-induced cardiac damage, as evidenced by decreases in short-term injury indicators including myocardial infarct size, cTnI release, myocardial apoptosis, cardiac HMGB1 expression, IL-6 and TNF-α production, as well as improvement on long-term cardiac function at 4 weeks post-reperfusion. These effects were partially reversed by either unilateral vagotomy or methyllycaconitine treatment. Besides, cardiac HMGB1-overexpression nearly abolished DEX-induced cardioprotection. Conclusions DEX pretreatment protects against myocardial I/R by inhibiting cardiac HMGB1 production and activating the cholinergic anti-inflammatory pathway.

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“…8 In addition, we showed the protective effects on cardiac myocytes when co-cultured with neonatal cardiac fibroblasts which are a major cellular component in the neonatal rat ventricle. 12 In this study, we evaluated the modulation of cardiac myocyte functional and biochemical changes by cardiac fibroblasts after hypothermic preservation using three types of storage solutions: saline solution, University of Wisconsin solution and MCDB 107 medium. The MCDB 107 medium has been shown to be an excellent medium for immature myocytes cultured under serum-free conditions 10 ' 12 and as used here provided complete protection from hypothermic injury for myocytes co-cultured with fibroblasts after 24 hours at 4 °C.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the viability of immature cardiac myocytes by cardiac fibroblasts after hypothermic preservation—its values as a technique for evaluation of storage solutions

et al. 1995

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We evaluated the modulation of the viability of immature cardiac myocytes by cardiac fibroblasts after hypothermic preservation using three types of storage solutions—saline, University of Wisconsin solution, and MCDB 107 medium. Cardiac myocytes and fibroblasts were isolated from neonatal rat ventricles, and cultures of myocytes only or co-cultures with fibroblasts (myocyte: fibroblast 2:1) were established. On the fourth day of culture, the cultures were incubated at 4 °C for 6, 12, 18 and 24 hours in the different storage solutions. Enzymes were measured in the storage solutions immediately before and after hypothermic incubation. The cultures were then incubated for an additional 24 hours at 37 °C to evaluate the recovery of the myocyte beating rate. The myocyte beating rate in the co-culture groups showed significantly higher recovery ratios than the corresponding groups in which only myocytes were cultured. Complete recovery was observed in the group co-cultured in MCDB medium 24 hours after hypothermic incubation (83.4% of control—beating rate prior to hypothermic incubation) compared to the other co-cultured groups (15.4, 0%, respectively). Release of enzymes in the co-cultures was significantly suppressed compared to the cultured myocytes, and the greatest suppression was found after 24 hours of incubation in MCDB medium (CPK: 36.6 mIU/flask, LDH: 281.2 mIU/flask) compared to the other two co-cultured groups (CPK: 181.1, 281.1; LDH: 501.7, 773.2). Cardiac fibroblasts diminished myocytic injury after hypothermic preservation using various storage solutions, in which MCDB 107 medium showed the best overall protective effect. Thus, cardiac fibroblasts may play an important role in controlling myocytic viability under various hypothermic conditions.

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Protection of Cardiac Myocytes from Hypothermic Injury by Cardiac Fibroblasts Isolated from Neonatal Rat Ventricle

Cited by 17 publications

References 0 publications

The relevance of non‐excitable cells for cardiac pacemaker function

The relevance of non‐excitable cells for cardiac pacemaker function

Dexmedetomidine-induced cardioprotection is mediated by inhibition of high mobility group box-1 and the cholinergic anti-inflammatory pathway in myocardial ischemia-reperfusion injury

Modulation of the viability of immature cardiac myocytes by cardiac fibroblasts after hypothermic preservation—its values as a technique for evaluation of storage solutions

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