Ischemia, rather than reperfusion, inhibits respiration through cytochrome oxidase in the isolated, perfused rabbit heart: role of cardiolipin

Lesnefsky, Edward J.; Chen, Qun; Slabe, Thomas J.; Stoll, Maria S.K.; Minkler, Paul E.; Hassan, Mahdi; Tandler, Bernard; Hoppel, Charles L.

doi:10.1152/ajpheart.00348.2003

Cited by 110 publications

(92 citation statements)

References 67 publications

(130 reference statements)

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“…During ischemia of the isolated perfused rabbit heart, SSM sustain a decrease in cardiolipin, cytochrome c, and oxidation through cytochrome oxidase (89). Reperfusion did not lead to additional damage in the distal electron transport chain in this model (81). Oxidation through cytochrome oxidase and the content of cytochrome c did not decrease further during reperfusion.…”

mentioning

confidence: 52%

“…Release of cytochrome c during ischemia activates downstream caspase 3 leading to an increase in the number of cardiomyocytes displaying apoptotic markers (21) that becomes increasingly evident during reperfusion (21, 25, 53, 63). In the isolated perfused rabbit heart, the decrease in mitochondrial cytochrome c content occurs during ischemia, without additional decreases during reperfusion (81). Thus injury to mitochondria during ischemia is sufficient to release cytochrome c for activation of apoptotic pathways.…”

Section: Mitochondria As Sources Of Cardiac Injury During Ischemiamentioning

confidence: 99%

“…Oxidation through cytochrome oxidase and the content of cytochrome c did not decrease further during reperfusion. Ischemic injury led to persistent defects in oxidative phosphorylation during the early reperfusion period (81,88). The decrease in cardiolipin content accompanied by persistent decrements in the content of cytochrome c and oxidation through cytochrome oxidase is a potential mechanism of additional myocyte injury during reperfusion.…”

mentioning

confidence: 99%

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Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion

Chen

Camara

Stowe

et al. 2007

American Journal of Physiology-Cell Physiology

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237

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Chen Q, Camara AK, Stowe DF, Hoppel CL, Lesnefsky EJ. Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion. Am J Physiol Cell Physiol 292: C137-C147, 2007. First published September 13, 2006; doi:10.1152/ajpcell.00270.2006.-Mitochondria are increasingly recognized as lynchpins in the evolution of cardiac injury during ischemia and reperfusion. This review addresses the emerging concept that modulation of mitochondrial respiration during and immediately following an episode of ischemia can attenuate the extent of myocardial injury. The blockade of electron transport and the partial uncoupling of respiration are two mechanisms whereby manipulation of mitochondrial metabolism during ischemia decreases cardiac injury. Although protection by inhibition of electron transport or uncoupling of respiration initially appears to be counterintuitive, the continuation of mitochondrial oxidative phosphorylation in the pathological milieu of ischemia generates reactive oxygen species, mitochondrial calcium overload, and the release of cytochrome c. The initial target of these deleterious mitochondrial-driven processes is the mitochondria themselves. Consequences to the cardiomyocyte, in turn, include oxidative damage, the onset of mitochondrial permeability transition, and activation of apoptotic cascades, all favoring cardiomyocyte death. Ischemia-induced mitochondrial damage carried forward into reperfusion further amplifies these mechanisms of mitochondrial-driven myocyte injury. Interruption of mitochondrial respiration during early reperfusion by pharmacologic blockade of electron transport or even recurrent hypoxia or brief ischemia paradoxically decreases cardiac injury. It increasingly appears that the cardioprotective paradigms of ischemic preconditioning and postconditioning utilize modulation of mitochondrial oxidative metabolism as a key effector mechanism. The initially counterintuitive approach to inhibit mitochondrial respiration provides a new cardioprotective paradigm to decrease cellular injury during both ischemia and reperfusion.cardiolipin; cytochrome c; complex I; cytochrome oxidase MITOCHONDRIA are both targets and sources of injury during cardiac ischemia and reperfusion. This review addresses the emerging concept that modulation of mitochondrial oxidative metabolism during ischemia or early reperfusion protects mitochondrial function and decreases myocardial cell death. Mitochondria contribute to their own damage during ischemia, since blockade of electron transport immediately before ischemia dramatically attenuates damage to mitochondrial electron transport, with preserved oxidative phosphorylation, retention of cytochrome c, and decreased release of reactive oxygen species (ROS). Ischemic preconditioning (IPC) leads to a partial uncoupling of mitochondrial respiration, resulting in decreased mitochondrial injury following subsequent sustained ischemia. A substantial portion of damage to mitochondrial electron transport and oxi...

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mentioning

confidence: 52%

Section: Mitochondria As Sources Of Cardiac Injury During Ischemiamentioning

confidence: 99%

mentioning

confidence: 99%

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Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion

Chen

Camara

Stowe

et al. 2007

American Journal of Physiology-Cell Physiology

Self Cite

237

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“…In contrast with the above studies, ischemia alone in a perfused rabbit heart model revealed loss of cardiolipin content with decrements in oxidative metabolism. These authors suggest that the mechanisms involved occur through cytochrome oxidase and loss of cytochrome c in SSM independent of reperfusion damage (70). Taken together, these studies suggest that cardiac I/R influences both mitochondrial subpopulations.…”

Section: Pathological Influencementioning

confidence: 81%

Physiological and structural differences in spatially distinct subpopulations of cardiac mitochondria: influence of cardiac pathologies

Hollander

Thapa

Shepherd

2014

American Journal of Physiology-Heart and Circulatory Physiology

130

108

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“…Cold ischemia of donor organs is also associated with mitochondrial dysfunction and activation of mitochondrial apoptotic pathways (97). Mitochondrial cytochrome c oxidase subunit 1 (COX1) synthesis and activity were significantly reduced in a rat model of brain warm ischemia/reperfusion (92), and oxidative metabolism through cytochrome oxidase was decreased in a cardiac model of warm ischemia/reperfusion (67). In contrast, gene and protein expression of COX1 and mitochondrial ATP synthase 6/8 were upregulated in 13-lined ground squirrels kidneys during torpor (57), suggesting that mitochondria of hibernating species are resistant to injury during hypothermia and hypoperfusion.…”

Section: Renal Mitochondriamentioning

confidence: 99%

Renal adaptation during hibernation

Jani

Martin

Jain

et al. 2013

American Journal of Physiology-Renal Physiology

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Hibernators periodically undergo profound physiological changes including dramatic reductions in metabolic, heart, and respiratory rates and core body temperature. This review discusses the effect of hypoperfusion and hypothermia observed during hibernation on glomerular filtration and renal plasma flow, as well as specific adaptations in renal architecture, vasculature, the renin-angiotensin system, and upregulation of possible protective mechanisms during the extreme conditions endured by hibernating mammals. Understanding the mechanisms of protection against organ injury during hibernation may provide insights into potential therapies for organ injury during cold storage and reimplantation during transplantation.hibernation; kidney; torpor; metabolism; electrolytes MAMMALIAN HIBERNATORS EXHIBIT heterothermy during winter months, cycling through periods of low core body temperature (CBT) for days to weeks (22) during torpor, followed by periodic arousals when CBT is elevated to 37°C for ϳ12 h ( Fig. 1) (63). CBT during torpor can fall to as low as Ϫ3°C in arctic ground squirrels (7) or 2-10°C in temperate-zone hibernators (22). During torpor, hibernators undergo profound physiological changes, reducing their heart rate from a summertime level of 200 -300 to 3-5 beats/min (128), their respiratory rate from 100 -200 to 4 -6 breaths/min (33, 46) and their metabolic rate to as low as 1-5% of basal metabolic rate (47). During arousal, organs undergo rapid metabolic reactivation, reperfusion, and rewarming to near normal levels (22). After maintaining euthermia and high metabolic activity for 12-18 h, the hibernator reenters torpor (Figs. 1 and 2). This review will focus on the renal adaptations employed by hibernators that permit their kidneys to withstand extreme fluctuations in CBT and organ perfusion during winter heterothermy. Studies of hibernation have been conducted for over a century and the nomenclature used to describe the various stages of hibernation, and the criteria used to define stages of hibernation, have evolved. Earlier studies often simply compared "hibernating" with "nonhibernating," and both terms were variably used. Hibernating often meant mid-winter torpor but was also used to refer to animals that were aroused, either naturally or more often, artificially. Nonhibernating was used to denote midsummer euthermic animals or winter aroused animals (94). As a further complication in the nomenclatures used, some investigators examine monthly or seasonal changes whereas others examine changes that occur during one torpor-arousal cycle of a few days duration. More recent studies have employed specific definitions of stages, representing both seasonal and torpor-arousal cycles, based on CBT monitoring using radiotelemetry (62,63,70,83) (Fig. 1). In addition, torpor can occur daily (referred to as "daily torpor" in "daily heterotherms") or over several days to weeks typically during winter in hibernators (46,125). For the purposes of this review we will 1) focus on renal function in hibernators that e...

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Ischemia, rather than reperfusion, inhibits respiration through cytochrome oxidase in the isolated, perfused rabbit heart: role of cardiolipin

Cited by 110 publications

References 67 publications

Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion

Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion

Physiological and structural differences in spatially distinct subpopulations of cardiac mitochondria: influence of cardiac pathologies

Renal adaptation during hibernation

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