Cardioprotection with ischemic preconditioning and MLA: Role of adenosine-regulating enzymes?

Karin Przyklenk, Lin Zhao, Robert A. Kloner, Gary T. Elliott

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39 Scopus citations


Both ischemic preconditioning and pretreatment with the endotoxin derivative monophosphoryl lipid A (MLA) protect the heart against infarction, yet the cellular mechanisms responsible for the cardioprotection achieved with either intervention are unknown. Using pentobarbital-anesthetized clogs, we tested the hypothesis that increased activity of 5'-nucleotidase (5'-NT), the enzyme that catalyzes the formation of adenosine from AMP, may play a role. Twenty-two dogs underwent 1 h of coronary occlusion and 4 h of reperfusion: eight controls received no intervention, seven animals were preconditioned with four 5-min episodes of brief ischemia, and seven received MLA (35 μg/kg iv) 24 h previously. Collateral blood flow was measured by injection of radiolabeled microspheres, infarct size was delineated by tetrazolium staining, and myocardial 5'-NT activities were measured by quantifying the release of adenosine from AMP. Despite comparable values of collateral blood flow in all groups, infarct size was reduced in preconditioned and MLA-treated dogs vs. controls. In addition, 5'-NT activities were increased throughout the heart with preconditioning and MLA treatment. However, single and multivariate regression analyses revealed no correlation between infarct size and 5'-NT activities for either treatment group. In fact, in the preconditioned cohort, animals with the highest enzyme activities developed the largest infarcts. This dissociation between infarct size and 5'-NT suggests that increased activity of 5'-NT is not the mechanism by which preconditioning or MLA treatment protects the canine heart against infarction.

Original languageEnglish
Pages (from-to)H1004-H1014
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number3 40-3
StatePublished - Sep 1996


  • 5'-nucleotidase
  • adenosine kinase
  • myocardial infarction
  • myocardial ischemia


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