Cardiovascular Research Advance Access [Accepted Manuscript] published online on October 1, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn260
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Delayed recovery of intracellular acidosis during reperfusion prevents calpain activation and determines protection in postconditioned myocardium
Laboratorio de Cardiología Experimental, Servicio de Cardiología, Hospital Universitari Vall d'Hebron, Barcelona, Spain
Corresponding author: Dr. David Garcia-Dorado Servicio de Cardiologia Hospital Universitari Vall d'Hebron Passeig Vall d'Hebron, 119-129 08035 Barcelona, Spain Ph:+34-93-4894038 Fax:+34-93-4894032 E-mail: dgdorado{at}vhebron.net
Aims: Indirect data suggest that delayed recovery of intracellular pH (pHi) during reperfusion is involved in postconditioning protection, and calpain activity has been shown to be pH dependent. We sought to characterize the effect of ischemic postconditioning on pHi recovery during reperfusion and on calpain-dependent proteolysis, an important mechanism of myocardial reperfusion injury.
Methods: Isolated Sprague-Dawley rat hearts were submitted to 40 minutes of ischemia and different reperfusion protocols of postconditioning and acidosis. Intracellular pH was monitored by 31P-NMR spectroscopy. Myocardial cell death was determined by lactate dehydrogenase (LDH) and triphenyltetrazolium staining and calpain activity by Western blot measurement of 
-fodrin degradation.
Results: In control hearts pHi recovered within 1.5±0.24 minutes of reperfusion. Postconditioning with 6 cycles of 10-second ischemia-reperfusion slightly delayed pHi recovery to 2.5±0.2 minutes and failed to prevent calpain-mediated -fodrin degradation or to elicit protection. Lowering perfusion flow to 50% during reperfusion cycles or shortening the cycles (12 cycles of 5-second ischemia-reperfusion) resulted in a further delay in pHi recovery (4.1±0.2 and 3.5±0.3 minutes, respectively), attenuated -fodrin proteolysis, improved functional recovery and reduced LDH release (47% and 38%, respectively, P<0.001) and infarct size (36% and 32%, respectively, P<0.001). This cardioprotection was identical to that produced by lowering the pH of the perfusion buffer to 6.4 during the first 2 minutes of reperfusion or by calpain inhibition with MDL-28170.
Conclusions: These results provide direct evidence that postconditioning protection depends on prolongation of intracellular acidosis during reperfusion and indicate that inhibited calpain activity could contribute to this protection.
Time for primary review: 28 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Inserte, J. A. Barrabes, V. Hernando, and D. Garcia-Dorado Orphan targets for reperfusion injury Cardiovasc Res, July 15, 2009; 83(2): 169 - 178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Garcia-Dorado, M. Ruiz-Meana, and H. M. Piper Lethal reperfusion injury in acute myocardial infarction: facts and unresolved issues Cardiovasc Res, July 15, 2009; 83(2): 165 - 168. [Full Text] [PDF]
|
|