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dc.contributor.authorFenton, Richard A.
dc.contributor.authorGaleckas, K. J.
dc.contributor.authorDobson, James G. Jr.
dc.date2022-08-11T08:10:16.000
dc.date.accessioned2022-08-23T17:02:13Z
dc.date.available2022-08-23T17:02:13Z
dc.date.issued1995-10-01
dc.date.submitted2008-06-12
dc.identifier.citationJ Mol Cell Cardiol. 1995 Oct;27(10):2373-83.
dc.identifier.issn0022-2828 (Print)
dc.identifier.pmid8576951
dc.identifier.urihttp://hdl.handle.net/20.500.14038/44170
dc.description.abstractHigh levels of norepinephrine in the heart are cardiotoxic resulting in contractile dysfunction and arrhythmic activity via beta-adrenoceptor mediated mechanisms. A low flow heart model perfused with physiological saline containing glucose and bubbled with an O2 gas mixture was used to determine whether adenosine, a nucleoside with antiadrenergic properties, could reduce the functional manifestations of catecholamine cardiotoxicity. Isolated rat hearts were treated with dipropylcyclopentylxanthine (DPCPX; 0.1 microM; A1 receptor antagonist) to block endogenous adenosine. In DPCPX-treated hearts stimulated with isoproterenol (ISO; 1 microM) during 45 min of low flow (0.5 ml/min) perfusion, the recovery of contractile function (ConF) at 15 min after the restoration of normal flow was 64% of control (before low flow) values as compared to 110% recovery of ConF in the absence of ISO. The incidence of arrhythmias observed upon restoration of control flow was increased by ISO when the action of endogenous adenosine was blocked with DPCPX. In the absence of DPCPX both the functional depression and arrhythmias induced by ISO were prevented in the presence of phenylisopropyladenosine (PIA; 1 microM; A1 receptor agonist). At 15 min after normal flow was restored. ConF in ISO-treated hearts with PIA was 53% greater than in the absence of PIA and presence of DPCPX. This enhancement of ConF by PIA was significantly reduced by DPCPX. By 30 min after flow restoration, these significant differences were absent. DPCPX reversed the PIA-induced reduction in arrhythmias observed upon restoration of normal flow. PIA and DPCPX alone in the absence of ISO, and ISO in the absence of PIA and DPCPX, did not result in altered ConF upon restoration of normal flow. These findings indicate that intense beta-adrenergic stimulation of the heart during low-flow perfusion in the absence of adenosine A1 receptor activity induces contractile depression and arrhythmicity subsequent to restoration of control perfusion. It is concluded that endogenous adenosine protects the heart against catecholamine toxicity via stimulation of adenosine A1 receptors.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8576951&dopt=Abstract ">Link to article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1016/S0022-2828(95)92055-2
dc.subjectAdenosine
dc.subjectAdrenergic beta-Agonists
dc.subjectAnimals
dc.subjectArrhythmias, Cardiac
dc.subjectCoronary Circulation
dc.subjectEpinephrine
dc.subjectIsoproterenol
dc.subjectMale
dc.subjectMyocardial Contraction
dc.subjectMyocardial Ischemia
dc.subjectMyocardial Reperfusion Injury
dc.subjectPerfusion
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectReceptors, Adrenergic, beta
dc.subjectReceptors, Purinergic P1
dc.subjectXanthines
dc.subjectCardiovascular Diseases
dc.subjectCellular and Molecular Physiology
dc.subjectPhysiology
dc.titleEndogenous adenosine reduces depression of cardiac function induced by beta-adrenergic stimulation during low flow perfusion
dc.typeJournal Article
dc.source.journaltitleJournal of molecular and cellular cardiology
dc.source.volume27
dc.source.issue10
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/physio_pp/51
dc.identifier.contextkey523467
html.description.abstract<p>High levels of norepinephrine in the heart are cardiotoxic resulting in contractile dysfunction and arrhythmic activity via beta-adrenoceptor mediated mechanisms. A low flow heart model perfused with physiological saline containing glucose and bubbled with an O2 gas mixture was used to determine whether adenosine, a nucleoside with antiadrenergic properties, could reduce the functional manifestations of catecholamine cardiotoxicity. Isolated rat hearts were treated with dipropylcyclopentylxanthine (DPCPX; 0.1 microM; A1 receptor antagonist) to block endogenous adenosine. In DPCPX-treated hearts stimulated with isoproterenol (ISO; 1 microM) during 45 min of low flow (0.5 ml/min) perfusion, the recovery of contractile function (ConF) at 15 min after the restoration of normal flow was 64% of control (before low flow) values as compared to 110% recovery of ConF in the absence of ISO. The incidence of arrhythmias observed upon restoration of control flow was increased by ISO when the action of endogenous adenosine was blocked with DPCPX. In the absence of DPCPX both the functional depression and arrhythmias induced by ISO were prevented in the presence of phenylisopropyladenosine (PIA; 1 microM; A1 receptor agonist). At 15 min after normal flow was restored. ConF in ISO-treated hearts with PIA was 53% greater than in the absence of PIA and presence of DPCPX. This enhancement of ConF by PIA was significantly reduced by DPCPX. By 30 min after flow restoration, these significant differences were absent. DPCPX reversed the PIA-induced reduction in arrhythmias observed upon restoration of normal flow. PIA and DPCPX alone in the absence of ISO, and ISO in the absence of PIA and DPCPX, did not result in altered ConF upon restoration of normal flow. These findings indicate that intense beta-adrenergic stimulation of the heart during low-flow perfusion in the absence of adenosine A1 receptor activity induces contractile depression and arrhythmicity subsequent to restoration of control perfusion. It is concluded that endogenous adenosine protects the heart against catecholamine toxicity via stimulation of adenosine A1 receptors.</p>
dc.identifier.submissionpathphysio_pp/51
dc.contributor.departmentDepartment of Physiology
dc.source.pages2373-83


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