Document Detail


Beta-adrenergic signal transduction and contractility in the canine heart after cardiopulmonary bypass.
MedLine Citation:
PMID:  9463634     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Impaired beta-adrenergic signal transduction has been proposed as a mechanism contributing to myocardial depression after cardiac surgery. This study determined the changes in the beta-adrenergic system in a model of postoperative myocardial dysfunction induced by myocardial ischaemia and reperfusion under cardiopulmonary bypass (CPB). Those changes were then related to contractility and responsiveness to beta-adrenergic stimulation. METHODS: Four groups of dog hearts were studied: 7 hearts harvested immediately after anaesthesia induction (control group representing the preoperative cardiac condition); 6 hearts harvested after three hours of chest opening by sternotomy (open chest group serving as control for the effects of anaesthesia and surgery); 7 hearts harvested during CPB after 30 minutes of global ischaemia (ischaemia group); and 10 hearts from dogs submitted to one hour of CPB involving 30 minutes of global cardiac ischaemia, harvested 30 minutes after CPB (ischaemia-reperfusion group). Myocardial membranes were prepared to assess: (1) beta-adrenergic receptor density using the radioligand [125I]iodocyanopindolol; (2) GTP-sensitive adenylate cyclase activity and its regulation by isoprenaline and forskolin; (3) G protein levels, using an immunoblotting technique. Ventricular trabeculae or papillary muscles served to assess contractility and responsiveness to isoprenaline. RESULTS: The control and open chest groups had comparable beta-adrenergic receptor density, adenylate cyclase activity and cardiac contractility. In the ischaemia group, the left ventricular membranes had a 55% decrease in receptor density as compared to the controls (P < 0.005), similar GTP-sensitive adenylate cyclase activity and significantly lower adenylate cyclase responses to stimulation with isoprenaline and forskolin. In the ischaemia-reperfusion group, a 144% increase in the left ventricular receptor density was found as compared to the controls (P < 0.005), with a 70% increase in GTP-sensitive adenylate cyclase activity (P < 0.05), a similar adenylate cyclase response to isoprenaline and a 61% increase in response to forskolin (P < 0.005). As compared to the controls, the ischaemia and ischaemia-reperfusion groups had comparable Gs alpha levels, but markedly decreased Gi alpha-2 and Gi alpha-3 levels. The baseline tension of the isolated muscles in the ischaemia and ischaemia-reperfusion groups was comparable, but was 61% and 47% lower than the controls, respectively (P < 0.05). The maximal isoprenaline stimulated tension in the ischaemia and ischaemia-reperfusion groups was 66% and 36% lower than the controls, respectively (P < 0.05 between all groups). CONCLUSIONS: The beta-adrenergic system is severely depressed during global cardiac ischaemia under CPB, but recovers to supranormal values after CPB. However the increased cAMP generation by myocardial membranes after CPB is associated with decreased tension generation by corresponding cardiac muscles. Thus decreased contractility after CPB may be better explained by cellular alterations distal to cAMP generation rather than by changes in the beta-adrenergic system.
Authors:
J Y Dupuis; K Li; A Calderone; H Gosselin; X P Yang; M B Anand-Srivastava; J Teijeira; J L Rouleau
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cardiovascular research     Volume:  36     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1998-02-27     Completed Date:  1998-02-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  223-35     Citation Subset:  IM    
Affiliation:
Department of Anaesthesia, University of Sherbrooke, Québec, Canada. jdupuis@heartinst.on.ca
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MeSH Terms
Descriptor/Qualifier:
Adenylate Cyclase / metabolism
Adrenergic beta-Agonists / pharmacology
Analysis of Variance
Animals
Cardiopulmonary Bypass*
Cell Membrane / metabolism
Dogs
Forskolin / pharmacology
GTP-Binding Proteins / metabolism
Immunoblotting
Isoproterenol / pharmacology
Myocardial Contraction / drug effects
Myocardial Ischemia / metabolism*,  surgery
Myocardial Reperfusion Injury / metabolism*
Myocardium / metabolism*
Postoperative Period
Radioligand Assay
Receptors, Adrenergic, beta / metabolism*
Signal Transduction*
Chemical
Reg. No./Substance:
0/Adrenergic beta-Agonists; 0/Receptors, Adrenergic, beta; 66428-89-5/Forskolin; 7683-59-2/Isoproterenol; EC 3.6.1.-/GTP-Binding Proteins; EC 4.6.1.1/Adenylate Cyclase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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