MYOCARDIAL ISCHEMIA From mechanisms to therapeutic potentials pptx

[...]... that can also occur during ischemia. '^ Opening of the MPTP leads to the release of cytochrome c, Smac/DIABLO, endonuclease G (EndoG) and apoptosis-inducing factor (AIF) all of which facilitate the apoptosis signaling ^^' ^"^ Figure 1 Cytochrome c is a catalytic scavenger for the mitochondrial superoxide and loss of cytochrome c results in inactivation of mitochondrial respiratory chain, reactive oxygen... Bcl-xL which are anti-apoptotic while Bax, Bad, Bid, Bim are pro-apoptotic Pro-apoptotic and anti-apoptotic Bcl-2 proteins can bind directly to the components of mitochondrial pore, leading to either its opening or closure respectively.'^ Figure 1 Alternatively, pro-apoptotic members, such as Bak or Bax, insert into the outer mitochondrial membrane where they oligomerize to form a permeable pore.'^... inhibit the respiratory chain with complex I activity to be lower in less severe ischemia and complex IV activity to be reduced in severe ischemia. "*^ Mitochondrial changes during ischemia and reperfiision result in increased production and accumulation of reactive oxygen species The energy transport firom mitochondria to cytosol is also impaired Adenine nucleotide translocase and mitochondrial creatine... GJ communication See also chapter 4 1.2.2 The inflammatory response Myocardial ischemia is associated with an inflammatory response that fiirther contributes to myocardial injury and ultimately leads to myocardial healing and scar formation Myocardial necrosis has been associated with complement activation and free radical generation that trigger cytokine cascades and upregulate chemokines expression... shown to peak after 24h of reperfusion and apoptotic cell death was increased up to 72 h of reperfusion, in a canine model of ischemia and reperfusion.^ Furthermore, apoptotic cell death can evolve into necrotic cell death and pharmacological inhibition of the apoptotic signaling cascade during the reperfusion phase is able to attenuate both the apoptotic and necrotic components of cell death.^'^ Apoptosis... entry into the cell, reviewed by Carmeliet.^^ C3^osolic potassium also decreases due to the opening of mitochondrial ATP depended potasium channels (K^jp)- Mitochondrial K^^ channels are activated during ischemia and may serve an important role in the adaptive response of the cell to ischemic stress ^^ Magnesium increases in cytosol due to the hydrolysis of ATP to which magnesium is bound and from inadequate... are all shown to reduce myocardial contractility acting in synergistic and cascade-like reactions The heart is a tumor necrosis factor-a producing organ (TNF-a) TNF-a is produced in response to stress Macrophages and cardiac myocytes themselves synthesize TNF-a and TNF-a is also released by mast cells TNF-a is an autocrine contributor to myocardial dysfiinction and cardiomyocyte death in ischemia and... injury is determined by various factors; the severity of ischemia (low-flow vs zero-flow ischemia) , the duration of ischemia, the temporal sequence of ischemia (short ischemia followed by long ischemia) , changes in metabolic and physical environment (hypothermia vs normothermia, preischemic myocardial glycogen content, perfusate composition) as well as the inflammatory response Reperfusion generally... required for transportation of ATP from the mitochondria to the cytosol) is reduced with subsequent impaired ATP transportation into the sites of utilization ATP in the mitochondrial matrix is hydrolyzed by the reversal of the ATP synthase, reviewed by Opie."*^ Selective inhibition of TCA cycle enzymes aconitase and a-ketoglutarate dehydrogenase, both known to be sensitive to in vitro oxidative modification... the expression of NHEl is found to be decreased in the non infarcted myocardium in a rat model of acute myocardial infarction.^^ Furthermore, mice with a null mutation in the NHEl exchanger are resistant to ischemia and reperfiision injury.^"* MYOCARDIAL ISCHEMIA 19 CDg . C. Pantos, G. Heusch, H. Taegtmeyer: Myocardial Ischemia: From mechanisms to therapeutic potentials. 2005 ISBN 0-387-28657-8 elSBN 0-387-28658-6 MYOCARDIAL ISCHEMIA From mechanisms to therapeutic. Germany Houston, Texas USA Library of Congress Cataloging-in-Publication Data Myocardial ischemia: from mechanisms to therapeutic potentials / edited by D.V. Cokkinos, C. Pantos, G. Heusch. 83 15. INSULIN LIKE GROWTH FACTOR (IGF-1) 85 16. PEROXISOME PROLIFERATED -ACTIVATED RECEPTORS (PPARS) 85 MYOCARDIAL ISCHEMIA: FROM MECHANISMS TO THERAPEUTIC POTENTIALS vii 17. THYROID HORMONE