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Ischaemic preconditioning is related to decreasing levels of extracellular adenosine that may be metabolically useful in the at‐risk myocardium: an experimental study in the pig
Author(s) -
Waldenström A.,
Haney M.,
Biber B.,
Kavianipour M.,
Moritz T.,
Strandén P.,
Wikström G.,
Ronquist G.
Publication year - 2010
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2009.02071.x
Subject(s) - adenosine , microdialysis , ischemia , adenylate kinase , ischemic preconditioning , purine , purine nucleoside phosphorylase , adenosine triphosphate , chemistry , extracellular , nucleoside , adenosine monophosphate , pharmacology , medicine , biochemistry , enzyme
Aim: ‘Pre‐treatment’ with short repetitive periods of ischaemia (ischaemic preconditioning) has proved to be a powerful mechanism for modification of the extent of myocardial damage following acute coronary artery occlusion. The exact mechanism of protection induced by ischaemic preconditioning is not known. We herewith put forward a contributing component for protection with preconditioning involving a shift in the adenylate kinase (AK) equilibrium reaction in favour of adenosine triphosphate (ATP) formation. Methods: A coronary artery was occluded in anaesthetized thoracotomized pigs to induce ischaemic preconditioning as well as a longer period of ischaemia. Microdialysis probes were inserted in ischaemic and control myocardium and were infused with 14 C‐ adenosine with two different specific activities. 14 C‐lactate was identified and measured in the effluent. Results: 14 C‐adenosine was taken up by non‐preconditioned and preconditioned myocardium during ischaemia. Significantly increased levels of 14 C‐lactate were recovered in preconditioned myocardium. 14 C‐adenosine with high specific activity resulted in a specific activity of lactate that was 2.7 times higher than that of lactate after administration of 14 C‐adenosine with low specific activity. Mass spectrography verified the identity of 14 C‐lactate. Conclusions: Preconditioning up‐regulates a new metabolic pathway (starting with 5′‐nucleotidase and ending up with lactate) resulting in ATP formation in the micromolar range on top of another effect terminating in a useful shift in the AK equilibrium reaction in favour of ATP generation in the millimolar range. Although the up‐regulation of the purine nucleoside phosphorylase pathway is clearly demonstrated, its biological relevance remains to be proved.