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dc.contributor.authorLankford, Amyen_US
dc.contributor.authorYang, Jing Ningen_US
dc.contributor.authorRose'Meyer, Roselynen_US
dc.contributor.authorFrench, Brenten_US
dc.contributor.authorMatherne, G Paulen_US
dc.contributor.authorFredholm, Bertilen_US
dc.contributor.authorYang, Zequanen_US
dc.description.abstractActivation of A1 adenosine receptors (A1ARs) may be a crucial step in protection against myocardial ischemia-reperfusion (I/R) injury; however, the use of pharmacological A1AR antagonists to inhibit myocardial protection has yielded inconclusive results. In the current study, we have used mice with genetically modified A1AR expression to define the role of A1AR in intrinsic protection and ischemic preconditioning (IPC) against I/R injury. Normal wild-type (WT) mice, knockout mice with deleted (A1KO-/-) or single-copy (A1KO+/-) A1AR, and transgenic mice (A1TG) with increased cardiac A1AR expression underwent 45 min of left anterior descending coronary artery occlusion, followed by 60 min of reperfusion. Subsets of each group were preconditioned with short durations of ischemia (3 cycles of 5 min of occlusion and 5 min of reperfusion) before index ischemia. Infarct size (IF) in WT, A1KO+/-, and A1KO-/- mice was (in % of risk region) 58 ᠳ, 60 ᠴ, and 61 ᠲ, respectively, and was less in A1TG mice (39 ᠴ, P < 0.05). A strong correlation was observed between A1AR expression level and response to IPC. IF was significantly reduced by IPC in WT mice (35 ᠳ, P < 0.05 vs. WT), A1KO+/- + IPC (48 ᠴ, P < 0.05 vs. A1KO+/-), and A1TG + IPC mice (24 ᠲ, P < 0.05 vs. A1TG). However, IPC did not decrease IF in A1KO-/- + IPC mice (63 ᠲ). In addition, A1KO-/- hearts subjected to global I/R injury demonstrated diminished recovery of developed pressure and diastolic function compared with WT controls. These findings demonstrate that A1ARs are critical for protection from myocardial I/R injury and that cardioprotection with IPC is relative to the level of A1AR gene expression.en_US
dc.publisherAmerican Physiology Societyen_US
dc.publisher.placeRockville Pike, Bethesda, MD, USAen_US
dc.relation.ispartofjournalAmerican Journal of Physiology (Heart and Circulatory Physiologyen_US
dc.titleEffect of modulating cardiac A1 adenosine receptor expression on protection with ischemic preconditioningen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.rights.copyrightSelf-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author[s] for more information.en_US
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