Document Detail


Cardiac beta-adrenergic neuroeffector systems in acute myocardial dysfunction related to brain injury. Evidence for catecholamine-mediated myocardial damage.
MedLine Citation:
PMID:  7554200     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Ten percent to 20% of potential cardiac donors with brain injury and no previous cardiac history have myocardial dysfunction. We assessed components of the beta-receptor-G-protein-adenylyl cyclase complex as well as the contractile response in 10 explanted acutely failing human hearts (donor heart dysfunction [DHD]) and compared the results with 13 age-matched nonfailing (NF) organ donor controls. METHODS AND RESULTS: As measured by echocardiography, all DHD hearts exhibited a decreased shortening fraction (16 +/- 2%, mean +/- SEM). Although total and subpopulation beta-receptor densities measured by [125I]iodocyanopindolol (ICYP) were similar in the DHD and NF groups, DHD hearts exhibited a 30% decrease in maximum isoproterenol-stimulated adenylyl cyclase activity and a 50% decrease in the maximal response to zinterol. DHD hearts also exhibited decreases in adenylyl cyclase maximal stimulation by forskolin (211 +/- 25 [DHD] versus 295 +/- 23 [NF] pmol cAMP.min-1.mg-1, P < .05) and 5'-guanylylimidodiphosphate (12.5 +/- 1.8 [DHD] versus 19.6 +/- 3.2 [NF] pmol cAMP.min-1.mg-1, P < .05), but there was no significant decrease in adenylyl cyclase stimulation by Mn2+, a direct activator of adenylyl cyclase. Right ventricular trabeculae removed from DHD hearts exhibited a profound decrease in the contractile response to isoproterenol (8.7 +/- 1 [DHD] versus 22 +/- 2 [NF] mN, P < .001) as well as reduced calcium responses (7.2 +/- 1.6 [DHD] versus 14 +/- 3 [NF] mN, P = .03). Morphological examination of two hearts revealed some ultrastructural evidence suggestive of catecholamine-mediated injury, but there was no difference in tissue creatine kinase activity between the two groups. CONCLUSIONS: Compared with NF hearts, DHD hearts exhibit marked uncoupling of beta 1- and beta 2-adrenergic receptors from adenylyl cyclase and contractile response stimulation as well as decreased intrinsic systolic function. Thus, acute myocardial dysfunction accompanying brain injury is characterized by marked alterations in beta-adrenergic signal transduction as well as changes in the contractile apparatus, and this profile is markedly different from what occurs in the chronically failing human heart.
Authors:
M White; R J Wiechmann; R L Roden; M B Hagan; M M Wollmering; J D Port; E Hammond; W T Abraham; E E Wolfel; J Lindenfeld
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  92     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1995 Oct 
Date Detail:
Created Date:  1995-11-14     Completed Date:  1995-11-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2183-9     Citation Subset:  AIM; IM    
Affiliation:
Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adenylate Cyclase / metabolism*
Adult
Brain Death / physiopathology*
Case-Control Studies
Catecholamines / metabolism*
Echocardiography
Female
GTP-Binding Proteins / metabolism*
Humans
Male
Myocardial Contraction / physiology*
Myocardium / metabolism,  pathology*
Receptors, Adrenergic, beta / physiology*
Signal Transduction
Tissue Donors
Ventricular Dysfunction, Left / etiology*,  physiopathology
Grant Support
ID/Acronym/Agency:
HL-13108/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Catecholamines; 0/Receptors, Adrenergic, beta; 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


Previous Document:  Silent cerebral infarction in patients with nonrheumatic atrial fibrillation. The Veterans Affairs S...
Next Document:  Noninvasive measurement of tissue magnesium and correlation with cardiac levels.