OBJECTIVE: Impaired beta-adrenergic signal transduction has been proposed as a mechanism contributing to @entity296 after cardiac surgery. This study determined the changes in the beta-adrenergic system in a model of postoperative @entity296 induced by @entity296 and reperfusion under cardiopulmonary bypass (CPB). Those changes were then related to contractility and responsiveness to beta-adrenergic stimulation. METHODS: Four groups of @entity235 hearts were studied: 7 hearts harvested immediately after anaesthesia induction (control group representing the preoperative @entity299 ); 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 @entity235 submitted to one hour of CPB involving 30 minutes of global @entity299 , harvested 30 minutes after CPB (ischaemia-reperfusion group). Myocardial membranes were prepared to assess: (1) beta-adrenergic receptor density using the radioligand [125I] @entity18013 ; (2) @entity3007 -sensitive adenylate cyclase activity and its regulation by @entity3044 and @entity1928 ; (3) G protein levels, using an immunoblotting technique. Ventricular trabeculae or papillary muscles served to assess contractility and responsiveness to @entity3044 . 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 @entity3007 -sensitive adenylate cyclase activity and significantly lower adenylate cyclase responses to stimulation with @entity3044 and @entity1928 . 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 @entity3007 -sensitive adenylate cyclase activity (P < 0.05), a similar adenylate cyclase response to @entity3044 and a 61% increase in response to @entity1928 (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 @entity3044 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 @entity308 during global @entity299 under CPB, but recovers to supranormal values after CPB. However the increased @entity268 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 @entity268 generation rather than by changes in the beta-adrenergic system.

Beta-adrenergic signal transduction and contractility in the XXXX heart after cardiopulmonary bypass.

@entity3007 :: ('MESH:D006160', 'Chemical') :: ['GTP'] @entity268 :: ('CHEBI:17489', 'Chemical') :: ['cAMP'] @entity296 :: ('MESH:D009202', 'Disease') :: ['myocardial ischaemia', 'myocardial depression', 'myocardial dysfunction'] @entity308 :: ('MESH:D003866', 'Disease') :: ['depressed'] @entity18013 :: ('MESH:D020120', 'Chemical') :: ['iodocyanopindolol'] @entity235 :: ('9615', 'Species') :: ['dog', 'dogs'] @entity299 :: ('MESH:D006331', 'Disease') :: ['cardiac ischaemia', 'cardiac condition'] @entity3044 :: ('MESH:D007545', 'Chemical') :: ['isoprenaline'] @entity1928 :: ('MESH:D005576', 'Chemical') :: ['forskolin']
@entity235 :: (9615,Species) :: ['canine']
