Abstract:
:The mitochondrial electrochemical gradient (Δp), which comprises the pH gradient (ΔpH) and the membrane potential (ΔΨ), is crucial in controlling energy transduction. During myocardial ischemia and reperfusion (IR), mitochondrial dysfunction mediates superoxide (·O2-) and H2O2 overproduction leading to oxidative injury. However, the role of ΔpH and ΔΨ in post-ischemic injury is not fully established. Here we studied mitochondria from the risk region of rat hearts subjected to 30 min of coronary ligation and 24 h of reperfusion in vivo. In the presence of glutamate, malate and ADP, normal mitochondria (mitochondria of non-ischemic region, NR) exhibited a heightened state 3 oxygen consumption rate (OCR) and reduced ·O2- and H2O2 production when compared to state 2 conditions. Oligomycin (increases ΔpH by inhibiting ATP synthase) increased ·O2- and H2O2 production in normal mitochondria, but not significantly in the mitochondria of the risk region (IR mitochondria or post-ischemic mitochondria), indicating that normal mitochondrial ·O2- and H2O2 generation is dependent on ΔpH and that IR impaired the ΔpH of normal mitochondria. Conversely, nigericin (dissipates ΔpH) dramatically reduced ·O2- and H2O2 generation by normal mitochondria under state 4 conditions, and this nigericin quenching effect was less pronounced in IR mitochondria. Nigericin also increased mitochondrial OCR, and predisposed normal mitochondria to a more oxidized redox status assessed by increased oxidation of cyclic hydroxylamine, CM-H. IR mitochondria, although more oxidized than normal mitochondria, were not responsive to nigericin-induced CM-H oxidation, which is consistent with the result that IR induced ΔpH impairment in normal mitochondria. Valinomycin, a K+ ionophore used to dissipate ΔΨ, drastically diminished ·O2- and H2O2 generation by normal mitochondria, but less pronounced effect on IR mitochondria under state 4 conditions, indicating that ΔΨ also contributed to ·O2- generation by normal mitochondria and that IR mediated ΔΨ impairment. However, there was no significant difference in valinomycin-induced CM-H oxidation between normal and IR mitochondria. In conclusion, under normal conditions the proton backpressure imposed by ΔpH restricts electron flow, controls a limited amount of ·O2- generation, and results in a more reduced myocardium; however, IR causes ΔpH impairment and prompts a more oxidized myocardium.
journal_name
Basic Res Cardioljournal_title
Basic research in cardiologyauthors
Kang PT,Chen CL,Lin P,Chilian WM,Chen YRdoi
10.1007/s00395-017-0626-1subject
Has Abstractpub_date
2017-07-01 00:00:00pages
36issue
4eissn
0300-8428issn
1435-1803pii
10.1007/s00395-017-0626-1journal_volume
112pub_type
杂志文章abstract::Successive ischemic episodes are commonly seen in clinical and experimental cardiology. Although prolonged abnormalities of the canine myocardium have been described following a single ischemic episode, it is not known whether myocardial injury is cumulative following multiple ischemic episodes. Dogs were subjected to...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01908148
更新日期:1984-07-01 00:00:00
abstract:OBJECTIVE:Ischemic or hypoxic preconditioning has been shown, in multicellular preparations, to reduce post-ischemic injury. In the present study, we attempted to develop a model of preconditioning in isolated rat myocytes in order to facilitate investigation into the mechanism of preconditioning. METHODS:The protecti...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF00788907
更新日期:1996-05-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/BF02650357
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abstract::In Langendorff-perfused guinea pig hearts, local myocardial perfusion was evaluated by analysis of FITC-dextran-150 elution kinetics after bolus injection. Locally estimated half-times of the monoexponential elution curves showed good correlation with global undisturbed coronary flow. After ligation of the left anteri...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01935807
更新日期:1984-01-01 00:00:00
abstract::In open-chest pigs during severe myocardial ischemia [K+]e, [Ca2+]e and [H+]e increase, [Na+]e increases transiently reaching control values after 30 min. Extracellular osmolality of the ischemic area increases due to an H2O-shift from the ECS to the ICS. The increase of [Na+]e and [Ca2+]e must b explained by the shri...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01908341
更新日期:1981-07-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-014-0421-1
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journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/978-3-642-72497-8_8
更新日期:1993-01-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s003950070025
更新日期:2000-12-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907211
更新日期:1983-11-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-019-0743-0
更新日期:2019-08-06 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF02650352
更新日期:1989-01-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907132
更新日期:1990-07-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF02005340
更新日期:1982-07-01 00:00:00
abstract::Isolated rat hearts were perfused by the recirculating Langendorff mode under normoxic conditions for 60 min. The Krebs-Ringer buffer was supplemented with 10 mM glucose + 12 IU/l insulin and either [U-14C]-fructose-1,6-bisphosphate (together with 5 mM cold fructose-1,6-bisphosphate) or [U-14C]-fructose (together with...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF00804337
更新日期:1992-05-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s003950170025
更新日期:2001-09-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01906357
更新日期:1977-03-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-015-0474-9
更新日期:2015-03-01 00:00:00
abstract::For 219 children between 3 and 15 years with the most frequent congenital and acquired heart failures it was investigated in what way the STI differ consistently from the corresponding standard values. It was found that all the STI of children with cardiovascular diseases can vary from the normal values scaled by hear...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01906520
更新日期:1978-07-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::An ischaemia-like state in cultured heart cells has been obtained by markedly restricting the volume of extracellular medium combined with total deprivation of oxygen (anoxia) and glucose. Cellular injury, as reflected by the release of both cytoplasmic and lysosomal enzymes was significantly greater than during anoxi...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/978-3-662-08390-1_27
更新日期:1987-01-01 00:00:00
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更新日期:2012-09-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF02190601
更新日期:1991-05-01 00:00:00
abstract::Cardioprotection aims at infarct size reduction and improvement of clinical outcome from myocardial infarction. The translation of cardioprotection from preclinical and promising proof-of-concept studies to clinical benefit for patients has been largely disappointing. Almost all of these studies which did not translat...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/s00395-019-0756-8
更新日期:2019-10-15 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907058
更新日期:1987-03-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-012-0303-3
更新日期:2012-11-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/BF00810520
更新日期:1996-01-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF00788873
更新日期:1993-11-01 00:00:00
abstract::The success of therapies targeting myocardial reperfusion injury is limited, while the cardioprotective impact of mitigating ischemia-related damage remains less explored. We have recently shown in a pig model that the intravenous administration of a modified atorvastatin preparation during ischemia attenuates the ris...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-019-0760-z
更新日期:2019-11-28 00:00:00
abstract::Mobilization of triacylglycerol stored in heart cells is accomplished by the combined action of lysosomal (acid) lipase and microsomal monoacylglycerol lipase or carboxylesterase. Non(heparin)-releasable neutral or alkaline lipase is similar to non(readily)-releasable lipoprotein lipase (LPL). The enzyme is mainly loc...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01908026
更新日期:1984-05-01 00:00:00