• Cardiovascular research · Jan 2009

    Delayed recovery of intracellular acidosis during reperfusion prevents calpain activation and determines protection in postconditioned myocardium.

    • Javier Inserte, Ignasi Barba, Víctor Hernando, and David Garcia-Dorado.
    • Laboratorio de Cardiología Experimental, Servicio de Cardiología, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron, 119-129, 08035 Barcelona, Spain.
    • Cardiovasc. Res. 2009 Jan 1; 81 (1): 116-22.

    AimsIndirect 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 ischaemic postconditioning on pHi recovery during reperfusion and on calpain-dependent proteolysis, an important mechanism of myocardial reperfusion injury.Methods And ResultsIsolated Sprague-Dawley rat hearts were submitted to 40 min of ischaemia and different reperfusion protocols of postconditioning and acidosis. pHi was monitored by (31)P-NMR spectroscopy. Myocardial cell death was determined by lactate dehydrogenase (LDH) and triphenyltetrazolium staining, and calpain activity by western blot measurement of alpha-fodrin degradation. In control hearts, pHi recovered within 1.5 +/- 0.24 min of reperfusion. Postconditioning with 6 cycles of 10 s ischaemia-reperfusion delayed pHi recovery slightly to 2.5 +/- 0.2 min and failed to prevent calpain-mediated alpha-fodrin degradation or to elicit protection. Lowering perfusion flow to 50% during reperfusion cycles or shortening the cycles (12 cycles of 5 s ischemia-reperfusion) resulted in a further delay in pHi recovery (4.1 +/- 0.2 and 3.5 +/- 0.3 min, respectively), attenuated alpha-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 min of reperfusion or by calpain inhibition with MDL-28170.ConclusionThese 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.

      Pubmed     Free full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…