Document Detail

Role of the beta-adrenergic receptor kinase in myocardial dysfunction after brain death.
MedLine Citation:
PMID:  16214537     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Significant cardiac dysfunction after brain death leading to exclusion from procurement for cardiac transplantation is seen in up to 25% of potential organ donors in the absence of structural heart disease. The cause includes uncoupling of the myocardial beta-adrenergic receptor signaling system. The mechanism, however, has not yet been described. This study investigates our hypothesis that brain death causes acute activation of the betaAR kinase and leads to desensitization of myocardial beta-adrenergic receptors and impaired ventricular function. METHODS: Adult pigs underwent a sham operation or induction of brain death by means of subdural balloon inflation (n = 8 in each group). Cardiac function was assessed by using sonomicrometry at baseline and for 6 hours after the operation. beta-Adrenergic receptor signaling was assessed at 6 hours after the operation by measuring myocardial sarcolemmal membrane adenylate cyclase activity, beta-adrenergic receptor density, beta-adrenergic receptor kinase expression, and activity. RESULTS: Induction of brain death led to significantly decreased left ventricular systolic and diastolic function. Basal and isoproterenol-stimulated adenylate cyclase activity was blunted in the brain dead group compared with the sham-operated group (28.3 +/- 4.3 vs 48.3 +/- 7.6 pmol of cyclic adenosine x min(-1) [P = .01] and 54.8 +/- 9.6 vs 114.5 +/- 18 pmol of cyclic adenosine monophosphate x mg(-1) x min(-1) [P < .02]). There was no difference in beta-adrenergic receptor density between the brain dead and sham-operated groups. Myocardial beta-adrenergic receptor kinase expression was 3-fold greater in the brain dead versus sham-operated groups, and membrane beta-adrenergic receptor kinase activity was 2.5-fold greater in the brain dead group compared with that seen in the sham-operated group. CONCLUSION: Induction of brain death leads to significant left ventricular dysfunction in this porcine model. Cardiac beta-adrenergic receptors are clearly uncoupled after brain death, and our data suggest that the mechanism is acute increase of myocardial beta-adrenergic receptor kinase activity, leading to beta-adrenergic receptor desensitization and ventricular dysfunction.
Prakash K Pandalai; Jefferson M Lyons; Jodie Y Duffy; Kelly M McLean; Connie J Wagner; Walter H Merrill; Jeffrey M Pearl; Shahab A Akhter
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of thoracic and cardiovascular surgery     Volume:  130     ISSN:  1097-685X     ISO Abbreviation:  J. Thorac. Cardiovasc. Surg.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-10-10     Completed Date:  2005-12-22     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0376343     Medline TA:  J Thorac Cardiovasc Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1183-9     Citation Subset:  AIM; IM    
Department of Surgery, Section of Cardiothoracic Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio 46267-0558, USA.
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MeSH Terms
Brain Death / physiopathology*
Heart / physiopathology*
beta-Adrenergic Receptor Kinases / physiology*
Grant Support
5 T32 HL007382-29/HL/NHLBI NIH HHS; P021-040-N366//PHS HHS
Reg. No./Substance:
EC Receptor Kinases

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

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