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Titolo:
ALTERATION OF THE CYTOSOLIC-MITOCHONDRIAL DISTRIBUTION OF HIGH-ENERGYPHOSPHATES DURING GLOBAL MYOCARDIAL-ISCHEMIA MAY CONTRIBUTE TO EARLY CONTRACTILE FAILURE
Autore:
RAUCH U; SCHULZE K; WITZENBICHLER B; SCHULTHEISS HP;
Indirizzi:
UNIV DUSSELDORF,MED KLIN B,MOORENSTR 5 D-40225 DUSSELDORF GERMANY UNIV DUSSELDORF,MED KLIN B D-40225 DUSSELDORF GERMANY
Titolo Testata:
Circulation research
fascicolo: 4, volume: 75, anno: 1994,
pagine: 760 - 769
SICI:
0009-7330(1994)75:4<760:AOTCDO>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
NUCLEAR-MAGNETIC-RESONANCE; PERFORMANCE LIQUID-CHROMATOGRAPHY; CREATINE-KINASE REACTION; GUINEA-PIG HEARTS; ADENINE-NUCLEOTIDE; RAT-HEART; FREE MAGNESIUM; OXIDATIVE-PHOSPHORYLATION; INORGANIC-PHOSPHATE; INTRACELLULAR PH;
Keywords:
MYOCARDIAL ISCHEMIA; EARLY CONTRACTILE FAILURE; COMPARTMENTATION OF HIGH-ENERGY PHOSPHATES; ADP/ATP CARRIER; PHOSPHOCREATINE SHUTTLE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
63
Recensione:
Indirizzi per estratti:
Citazione:
U. Rauch et al., "ALTERATION OF THE CYTOSOLIC-MITOCHONDRIAL DISTRIBUTION OF HIGH-ENERGYPHOSPHATES DURING GLOBAL MYOCARDIAL-ISCHEMIA MAY CONTRIBUTE TO EARLY CONTRACTILE FAILURE", Circulation research, 75(4), 1994, pp. 760-769

Abstract

Depending on its duration, temporary myocardial ischemia leads to a disturbance of myocardial function before irreversible cellular necrosis is developed. Mechanical, electrical, and metabolic disturbances were suggested to be possible mechanisms accounting for the altered mechanical performance in ischemic hearts. To further investigate the alteration of myocardial energy metabolism on the subcellular level, we determined, by means of nonaqueous fractionation, the cytosolic-mitochondrial distribution of high-energy phosphates and other metabolites (ATP, ADP, phosphocreatine, creatine, and inorganic phosphate) in ischemic(zero-flow) guinea pig hearts after isolated perfused working heart preparation. Additional experiments using P-31 nuclear magnetic resonance spectroscopy were performed to determine pH(i) and [Mg2+](i) changes during global ischemia. The total ATP content of myocardial tissue dropped only slowly to 76% of control ATP at 10 minutes and to 51% at 30 minutes and reached almost zero at 60 minutes of ischemia. However, striking differences were observed on the subcellular level: While cytosolic phosphocreatine was almost completely consumed after 3 minutes of ischemia (from 19.1+/-1.6 to 3.3+/-0.5 mmol/L), ATP concentration in the cytosol decreased within 30 minutes from 8.4+/-0.6 to only 5.4+/-0.9 mmol/L. Mitochondrial ATP was rapidly and linearly reduced to 60%after 5 minutes of ischemia and was nearly unmeasurable after a further 20 minutes. Thus, in contrast to the breakdown of phosphocreatine in cytosol, the only slight alteration of cytosolic ATP reveals a reduction in cytosolic ATP utilization. Moreover, the unaffected cytosolic-mitochondrial difference in the phosphorylation potential of ATP demonstrates the intact function of the ADP/ATP carrier during early ischemia. These results might indicate a disturbance of the functional coupling between carrier and phosphocreatine kinase (phosphocreatine shuttle), which could be of importance for the early contractile failure in myocardial ischemia.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 14:31:11