Assessment of the cytoprotective role of adenosine in an in vitro cellular model of myocardial ischemia

Bés, Sandrine; Ponsard, Blandine; Asri, Mounia El; Tissier, Cindy; Vandroux, David; Rochette, Luc; Athias, Pierre

doi:10.1016/s0014-2999(02)02295-1

Cited by 12 publications

(2 citation statements)

References 37 publications

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“…Anti-ischemic effects of A 1 ARs appear direct (at cardiomyocytes), since similar protection is observed in isolated hearts, cardiomyocytes, and in vivo [28,32,35,37,49,52,54]. Protective A 2 AR effects involve modulation of vascular function, platelet adhesion and neutrophil activation [34,35,42,53,74], and are absent in cardiomyocytes [75] and in vitro models lacking blood [37,45,76]. Nonetheless, cardiomyocyte Adora2a mRNA expression [77], and functional A 2A AR responses in cardiomyocytes [77][78][79] implicate a functional myocardial A 2A AR (of obscure function).…”

Section: Intrinsic Cardioprotection Via Adenosine Receptors: Effects mentioning

confidence: 77%

Adenosine-mediated cardioprotection in the aging myocardium

Willems

Ashton

Headrick

2005

Cardiovascular Research

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With aging, it appears the heart's ability to withstand injury declines markedly. Unfortunately, the incidence of ischemic disorders increases dramatically with age. Though the genesis of the ischemia-intolerant phenotype is incompletely understood (and likely multi-factorial), it may involve changes in intrinsic cardioprotective responses. In this respect we and others have interrogated the role of the adenosine receptor (AR) system in dictating ischemic tolerance and the impact of age on AR-mediated cardioprotection. It is intriguing to note ARs impact on many processes implicated in myocardial 'aging': adenosine counters Ca2+ influx and oxidant injury, modifies substrate metabolism to improve tolerance, is pro-angiogenic, inhibits myocardial fibrosis, and can limit apoptosis. Thus, dysregulation of the AR system could contribute to many features of aged hearts (including ischemic intolerance). The latter is borne out by observations that AR-mediated protective responses decline with intrinsic tolerance and that transgenic manipulation of the AR system restores intrinsic tolerance and protective responses in aged hearts. Mechanisms underlying failure in adenosinergic protection remain undefined. Here we review data on the effects of aging on cardiovascular AR transcription and expression, generation of signal (adenosine formation), and protective signaling coupled to ARs.

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Section: Intrinsic Cardioprotection Via Adenosine Receptors: Effects mentioning

confidence: 77%

Adenosine-mediated cardioprotection in the aging myocardium

Willems

Ashton

Headrick

2005

Cardiovascular Research

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“…Indeed, the isolated CM model features limitations with respect to the highly complex, multifactorial nature of the in vivo situation. Firstly, this model lacks the potentially modulating influences of naturally neighboring cells and neurohumoral substances, although cultured CMs may release various bioactive substances during the ischemic insult, as observed in the intact myocardium (Bès et al 2002;Oudot et al 1994). Secondly, the contraction data in cell models are derived from cell-shortening measurements in lightly loaded conditions, which could dampen the time course and the magnitude of the metabolic stress.…”

Section: Full Ischemiamentioning

confidence: 99%

Specific electromechanical responses of cardiomyocytes to individual and combined components of ischemia

Tissier¹,

Bés²,

Vandroux³

et al. 2002

Can. J. Physiol. Pharmacol.

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The main factors of myocardial ischemia are hypoxia, substrate deprivation, acidosis, and high extracellular potassium concentration ([K+]e), but the influence of each of these factors has not yet been evaluated in a cardiomyocyte (CM) culture system. Electromechanical responses to the individual and combined components of ischemia were studied in CM cultured from newborn rat ventricles. Action potentials (APs) were recorded using glass microelectrodes and contractions were monitored photometrically. Glucose-free hypoxia initially reduced AP duration, amplitude, and rate and altered excitation-contraction coupling, but AP upstroke velocity (Vmax) remained unaffected. Early afterdepolarizations appeared, leading to bursts of high-rate triggered impulses before the complete arrest of electromechanical activity after 120 min. Acidosis reduced Vmax whereas AP amplitude and rate were moderately decreased. Combining acidosis and substrate-free hypoxia also decreased Vmax but attenuated the effects of substrate-free hypoxia on APs and delayed the cessation of the electrical activity (180 min). Raising [K+]e reduced the maximal diastolic potential and Vmax. Total ischemia (substrate deletion, hypoxia, acidosis, and high [K+]e) decreased AP amplitude and Vmax without changing AP duration. Moreover, delayed afterdepolarizations appeared, initiating triggered activity. Ultimately, 120 min of total ischemia blocked APs and contractions. To conclude, glucose-free hypoxia caused severe functional defects, acidosis delayed the changes induced by substrate-free hypoxia, and total ischemia induced specific dysfunctions differing from those caused by the former conditions. Heart-cell cultures thus represent a valuable tool to scrutinize the individual and combined components of ischemia on CMs.

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