Preconditioning does not prevent postischemic dysfunction in aging heart

Abete, Pasquale; Ferrara, Nicola; Cioppa, Angelo; Ferrara, Pietro; Bianco, S.; Calabrese, Claudio; Cacciatore, Francesco; Longobardi, Giancarlo; Rengo, Franco

doi:10.1016/0735-1097(96)00070-8

Cited by 160 publications

(100 citation statements)

References 43 publications

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“…The effect of aging on PC is unclear. Some studies [27,28,29] but not others [30] support the concept that the early PC response is absent in old animals. Aging abolishes the late phase of ischemia-induced PC in mice [31] but not the late phase of opioid-induced late PC in rats [32].…”

Section: Cox-2 Involvement In Pcmentioning

confidence: 99%

The late phase of preconditioning and its natural clinical application—gene therapy

Bolli

Tang

et al. 2007

Heart Fail Rev

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There is little doubt that the discovery of ischemic preconditioning (PC) has been one of the fundamental milestones in the field of ischemic biology in the past 20 years. The purpose of this article is to review the pathophysiology and molecular basis of the late phase of myocardial PC. The exploitation of late PC for the development of novel gene therapy strategies aimed at inducing a permanently preconditioned cardiac phenotype (prophylactic cardioprotection) will also be discussed. Deciphering the mechanism of late PC has not only conceptual interest but also a considerable therapeutic implications, since transfer of the genes that underlie late PC would be expected to replicate the salubrious effects of this response of the heart to stress.

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Section: Cox-2 Involvement In Pcmentioning

confidence: 99%

The late phase of preconditioning and its natural clinical application—gene therapy

Bolli

Tang

et al. 2007

Heart Fail Rev

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“…In addition, several experimental and clinical investigations have addressed the issue of whether IPC occurs in aged hearts (1,2,28,40,46). The efficacy of IPC has been reported to be decreased or lost in senescent patients (2,28) and in aged animals (1,40).…”

Section: Effect Of Cr On Myocardial Ischemia-reperfusion Injury and Ipcmentioning

confidence: 99%

“…Hearts from senescent animals are more susceptible to ischemia than those from young animals (7,20,45). Recently, a number of investigators have demonstrated that the cardioprotective effect of ischemic preconditioning (IPC) is impaired in aged animals (1,2,28,40,46). Aging also loses the cardioprotection afforded by postconditioning (8).…”

mentioning

confidence: 99%

Impact of 6-mo caloric restriction on myocardial ischemic tolerance: possible involvement of nitric oxide-dependent increase in nuclear Sirt1

Shinmura

Tamaki

Bolli

2008

American Journal of Physiology-Heart and Circulatory Physiology

114

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Ischemic tolerance decreases with aging, and the cardioprotective effect of ischemic preconditioning (IPC) is impaired in middle-aged animals. We have demonstrated that short-term caloric restriction (CR) improves myocardial ischemic tolerance in young and old animals via the activation of adiponectin-AMP-activated protein kinase (AMPK)-mediated signaling. However, it is unknown whether prolonged CR confers cardioprotection in a similar manner. Furthermore, little is known regarding the myocardial expression of silent information regulator 1 (Sirt1; which reportedly mediates various aspects of the CR response) with prolonged CR. Thus, 6-mo-old male Fischer-344 rats were randomly divided into ad libitum (AL) and CR groups. Six months later, isolated perfused hearts were subjected to 25 min of global ischemia followed by 120 min of reperfusion with or without IPC. CR improved the recovery of left ventricular function and reduced infarct size after ischemiareperfusion and restored the IPC effect. Serum adiponectin levels increased, but myocardial levels of total and phosphorylated AMPK did not change with prolonged CR. Total levels of Sirt1 did not change with CR; however, in the nuclear fraction, CR significantly increased Sirt1 and decreased acetyl-histone H3. Eleven rats from each group were given N-nitro-L-arginine methyl ester in their drinking water for 4 wk before death. In these hearts, chronic inhibition of nitric oxide synthase prevented the increase in nuclear Sirt1 content by CR and abrogated CR-induced cardioprotection. These results demonstrate that 1) prolonged CR improves myocardial ischemic tolerance and restores the IPC effect in middle-aged rats and 2) CR-induced cardioprotection is associated with a nitric oxidedependent increase in nuclear Sirt1 content. aging; myocardial ischemia; nutrition; preconditioning; reperfusion injury; silent information regulator 1

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“…Aging is associated with a progressive decline in physiological reserves that reduces the capacity for work (Chantler et al, 2006;Goldspink, 2005) and increases the susceptibility to injury (Abete et al, 1996;Juhaszova et al, 2005;Lesnefsky et al, 1994;Maggioni et al, 1993). A case in point is the myocardium, an aerobic tissue with high energy demands dependent on mitochondrial oxidative phosphorylation (OxPhos) where aging precipitates organ failure during stress.…”

Section: Introductionmentioning

confidence: 99%

Aging-induced alterations in gene transcripts and functional activity of mitochondrial oxidative phosphorylation complexes in the heart

Preston¹,

Oberlin²,

Holmuhamedov³

et al. 2008

Mechanisms of Ageing and Development

121

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Aging is associated with progressive decline in energetic reserves compromising cardiac performance and tolerance to injury. Although deviations in mitochondrial functions have been documented in senescent heart, the molecular bases for the decline in energy metabolism are only partially understood. Here, high-throughput transcription profiles of genes coding for mitochondrial proteins in ventricles from adult (6-months) and aged (24-months) rats were compared using microarrays. Out of 614 genes encoding for mitochondrial proteins, 94 were differentially expressed with 95% downregulated in the aged. The majority of changes affected genes coding for proteins involved in oxidative phosphorylation (39), substrate metabolism (14) and tricarboxylic acid cycle (6). Compared to adult, gene expression changes in aged hearts translated into a reduced mitochondrial functional capacity, with decreased NADH-dehydrogenase and F0F1-ATPase complex activities and capacity for oxygen-utilization and ATP synthesis. Expression of genes coding for transcription co-activator factors involved in the regulation of mitochondrial metabolism and biogenesis were downregulated in aged ventricles without reduction in mitochondrial density. Thus, aging induces a selective decline in activities of oxidative phosphorylation complexes I and V within a broader transcriptional downregulation of mitochondrial genes, providing a substrate for reduced energetic efficiency associated with senescence.

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Preconditioning does not prevent postischemic dysfunction in aging heart

Cited by 160 publications

References 43 publications

The late phase of preconditioning and its natural clinical application—gene therapy

The late phase of preconditioning and its natural clinical application—gene therapy

Impact of 6-mo caloric restriction on myocardial ischemic tolerance: possible involvement of nitric oxide-dependent increase in nuclear Sirt1

Aging-induced alterations in gene transcripts and functional activity of mitochondrial oxidative phosphorylation complexes in the heart

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