Age-related changes in ischemic tolerance in male and female mouse hearts

Willems, Laura; Zatta, Amanda J.; Holmgren, Kirsty; Ashton, Kevin J.; Headrick, John P.

doi:10.1016/j.yjmcc.2004.09.014

Cited by 97 publications

(111 citation statements)

References 70 publications

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“…This is in agreement with numerous studies showing that middle-aged and senescent hearts (Azhar et al 1999;Leichtweis et al 2001;Xia et al 2003;Willems et al 2003;Willems et al 2005) augment reperfusioninduced contraction disorders. Delayed ischemic contracture with preservation of residual metabolic activity might be responsible for these intensified abnormalities.…”

Section: Discussionsupporting

confidence: 93%

“…We observed lower recovery of the coronary flow of the middle-aged hearts compared with that of the young adults. This has been already mentioned by Willems et al (2005) who showed that impaired salvage of the ventricular contractility in reperfused hearts of senescent animals correlates with recovery of the coronary flow. Furthermore, Besse et al (2006) have shown that the post-ischemic coronary flow of the aged heart can be improved by treatment with superoxide dismutase and catalase, highlighting the prominent role of superoxide anions.…”

Section: Discussionsupporting

confidence: 53%

“…From data presented in the literature, the aged heart has a diminished functional and adaptive reserve capacity, an increased susceptibility to incur damage and a limited practical ability for repair/regeneration (Juhaszova et al 2005). The reduced tolerance to ischemic insult with aging is also noticed in the laboratory animal with a reduced recovery of the coronary flow and contractility during reperfusion occurring in mice (Azhar et al 1999;Willems et al 2003;Willems et al 2005) and rats (Leichtweis et al 2001;Xia et al 2003) as soon as they reach middle age.…”

Section: Introductionmentioning

confidence: 99%

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Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion

Mourmoura

Leguen

Dubouchaud

et al. 2010

AGE

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Aging compromises restoration of the cardiac mechanical function during reperfusion. We hypothesized that this was due to an ampler release of mitochondrial reactive oxygen species (ROS). This study aimed at characterising ex vivo the mitochondrial ROS release during reperfusion in isolated perfused hearts of middle-aged rats. Causes and consequences on myocardial function of the observed changes were then evaluated. The hearts of rats aged 10-or 52-week old were subjected to global ischemia followed by reperfusion. Mechanical function was monitored throughout the entire procedure. Activities of the respiratory chain complexes and the ratio of aconitase to fumarase activities were determined before ischemia and at the end of reperfusion. H 2 O 2 release was also evaluated in isolated mitochondria. During ischemia, middle-aged hearts displayed a delayed contracture, suggesting a maintained ATP production but also an increased metabolic proton production. Restoration of the mechanical function during reperfusion was however reduced in the middle-aged hearts, due to lower recovery of the coronary flow associated with higher mitochondrial oxidative stress indicated by the aconitase to fumarase ratio in the cardiac tissues. Surprisingly, activity of the respiratory chain complex II was better maintained in the hearts of middle-aged animals, probably because of an enhanced preservation of its membrane lipid environment. This can explain the higher mitochondrial oxidative stress observed in these conditions, since cardiac mitochondria produce much more H 2 O 2 when they oxidize FADH 2 -linked substrates than when they use NADH-linked substrates. In conclusion, the lower restoration of the cardiac mechanical activity during reperfusion in the middle-aged hearts was due to an impaired recovery of the coronary flow and an insufficient oxygen supply. The deterioration AGE (2011) of the coronary perfusion was explained by an increased mitochondrial ROS release related to the preservation of complex II activity during reperfusion.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion

Mourmoura

Leguen

Dubouchaud

et al. 2010

AGE

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“…It has been demonstrated in animal models that there is an apparent nadir in ischemic tolerance in middle-aged to aged hearts, with a subsequent modest improvement with senescence [6,7]. This pattern is consistent with empiric clinical observations and with prior studies showing an improvement in the senescent compared with the aged heart that may be related to selection of a subpopulation resistant to myocardial injury [6,7].…”

supporting

confidence: 83%

“…Our model was chosen because previous studies in animal models have shown that age-related ischemic intolerance develops well before senescence, being primarily evident by middle age [2,6,7]. It has been demonstrated in animal models that there is an apparent nadir in ischemic tolerance in middle-aged to aged hearts, with a subsequent modest improvement with senescence [6,7].…”

mentioning

confidence: 99%

Age- and Gender-Related Differences in Mitochondrial Oxygen Consumption and Calcium With Cardioplegia and Diazoxide

McCully

Rousou

Parker

et al. 2007

The Annals of Thoracic Surgery

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Background-We have recently shown that the cardioprotection afforded by cardioplegia is affected by age and gender and is less effective in the aged female rabbit heart compared with the aged male rabbit heart. We hypothesized that these differences were due to age and gender-specific modulation of mitochondrial oxygen consumption and mitochondrial free matrix calcium ([Ca 2+ ] Mito ) content occurring during early reperfusion.

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Mitochondrial Potassium Channels as Pharmacological Target for Cardioprotective Drugs

Testai

Rapposelli

Martelli

et al. 2014

Medicinal Research Reviews

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Brief periods of ischemia are known to confer to the myocardium an increased resistance to the injury due to a later and more prolonged ischemic episode. This phenomenon, known as ischemic preconditioning (IPreC), is ensured by different biological mechanisms. Although an exhaustive comprehension of them has not been reached yet, it is widely accepted that mitochondria are pivotally involved in controlling cell life and death, and thus in IPreC. Among the several signaling pathways involved, as triggers and/or end effectors, in the mitochondrial mechanisms of cardioprotection, an important role is played by the activation of potassium channels located in the mitochondrial inner membrane (mitoK) of cardiomyocytes. Presently, different types of mitoK channels have been recognized in the heart, such as ATP-sensitive (mitoKATP) and calcium-activated (mitoBK(Ca) and mitoSK(Ca)) potassium channels. Consistently, drugs modulating mitoK, on one hand, have been employed as useful experimental tools for early basic studies on IPreC. On the other hand, activators of mitoK are promising and innovative therapeutic agents for limiting the myocardial injury due to ischemic episodes. In this review, we report the experimental evidence supporting the role of mitoK in signaling pathways in the mechanisms of cardioprotection and an overview on the most important molecules acting as modulators of these channels, with their profiles of selectivity. Some innovative pharmaceutical strategies for mitochondriotropic drugs have been also reported. Finally, an appendix describing the main experimental approaches usually employed to study mitoK in isolated mitochondria or in intact cells has been added.

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Age-related changes in ischemic tolerance in male and female mouse hearts

Cited by 97 publications

References 70 publications

Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion

Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion

Age- and Gender-Related Differences in Mitochondrial Oxygen Consumption and Calcium With Cardioplegia and Diazoxide

Mitochondrial Potassium Channels as Pharmacological Target for Cardioprotective Drugs

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