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Effect of acidic reperfusion on prolongation of intracellular acidosis and myocardial salvage.

AbstractAIMS:
It has been proposed that intracellular acidosis may be the basis of the cardioprotection of different interventions, including postconditioning. However, contradictory reports exist on the effects of acidic reperfusion on myocardial salvage. Here we characterized the effect of lowering the pH of the reperfusion media (pHo) on intracellular pH (pHi) and cell death.
METHODS AND RESULTS:
The effect of acidic perfusion on reperfusion injury was studied in isolated rat hearts submitted to 40 min of ischaemia and 30 min of reperfusion, and its effect on the Na(+)/Ca(2+)-exchanger (NCX) was analysed in isolated myocytes. pHi and phosphocreatine (PCr) were monitored by nuclear magnetic resonance spectroscopy. Lowering pHo to 6.4 during the initial 3 min of reperfusion delayed pHi normalization, improved PCr recovery, and markedly reduced (P < 0.001) lactate dehydrogenase release and infarct size (tetrazolium reaction). This cardioprotection was attenuated as pHo was increased, and was lost at pH0 7.0. Extending acidic reperfusion to the first 15 or 30 min of reflow did not result in further delay of pHi normalization and abolished the protection afforded by the initial 3 min of acidic reperfusion unless the Na(+)/H(+)-exchanger (NHE) blocker cariporide was added to the acidic perfusate and HCO(3)(-) substituted for N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulphonic acid]. In experiments performed in fura-2-loaded myocytes exposed to low Na(+) buffer adjusted to pH 6.4, the lower Ca(2+) uptake indicated an inhibitory effect of acidosis on NCX.
CONCLUSION:
Acidic reperfusion for 3 min delays normalization of pHi and enhances myocardial salvage, but extending it beyond this period fails to further delay pHi recovery. This is probably due to persisting NHE and Na(+)/HCO(3)(-)-cotransporter activities, and it is detrimental, possibly through prolonged NCX inhibition.
AuthorsJavier Inserte, Ignasi Barba, Víctor Hernando, Arancha Abellán, Marisol Ruiz-Meana, Antonio Rodríguez-Sinovas, David Garcia-Dorado
JournalCardiovascular research (Cardiovasc Res) Vol. 77 Issue 4 Pg. 782-90 (Mar 01 2008) ISSN: 0008-6363 [Print] England
PMID18056767 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Buffers
  • Sodium-Bicarbonate Symporters
  • Sodium-Calcium Exchanger
  • Sodium-Hydrogen Exchangers
  • Phosphocreatine
  • L-Lactate Dehydrogenase
Topics
  • Acidosis (metabolism, pathology)
  • Animals
  • Buffers
  • Cell Death
  • Energy Metabolism
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • L-Lactate Dehydrogenase (metabolism)
  • Magnetic Resonance Spectroscopy
  • Male
  • Myocardial Infarction (metabolism, pathology, prevention & control)
  • Myocardial Reperfusion (methods)
  • Myocardial Reperfusion Injury (metabolism, pathology, prevention & control)
  • Myocardium (metabolism, pathology)
  • Myocytes, Cardiac (metabolism)
  • Phosphocreatine (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Bicarbonate Symporters (metabolism)
  • Sodium-Calcium Exchanger (metabolism)
  • Sodium-Hydrogen Exchangers (metabolism)
  • Time Factors

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