title: Hypertrophy of neurons within cardiac ganglia in human, canine, and rat heart failure: the potential role of nerve growth factor.
abstract: BACKGROUND
  Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hypertrophied in human, canine, and rat heart failure and that nerve growth factor, which we hypothesize is elevated in the failing heart, contributes to this neuronal hypertrophy.
  
  
  RESULTS
  Somal morphology of neurons from human (579.54±14.34 versus 327.45±9.17 μm(2); P<0.01) and canine hearts (767.80±18.37 versus 650.23±9.84 μm(2); P<0.01) failing secondary to ischemia and neurons from spontaneously hypertensive rat hearts (327.98±3.15 versus 271.29±2.79 μm(2); P<0.01) failing secondary to hypertension reveal significant hypertrophy of neurons in cardiac ganglia compared with controls. Western blot analysis shows that nerve growth factor levels in the explanted, failing human heart are 250% greater than levels in healthy donor hearts. Neurons from cardiac ganglia cultured with nerve growth factor are significantly larger and have greater dendritic arborization than neurons in control cultures.
  
  
  CONCLUSIONS
  Hypertrophied neurons are significantly less excitable than smaller ones; thus, hypertrophy of vagal postganglionic neurons in cardiac ganglia would help to explain the parasympathetic withdrawal that accompanies heart failure. Furthermore, our observations suggest that nerve growth factor, which is elevated in the failing human heart, causes hypertrophy of neurons in cardiac ganglia.
authors: Research Services, Hines VA Medical Center, Hines, IL.
authors: Sanjay
authors: S
authors: Singh
authors: Scott
authors: S
authors: Sayers
authors: James S
authors: JS
authors: Walter
authors: Donald
authors: D
authors: Thomas
authors: Robert S
authors: RS
authors: Dieter
authors: Lisa M
authors: LM
authors: Nee
authors: Robert D
authors: RD
authors: Wurster
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005725:Ganglia, Autonomic / Q000378:metabolism* / Q000473:pathology; D006321:Heart / Q000294:innervation*; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000150:complications; D006984:Hypertrophy; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: C502240:NGF protein, human; D020932:Nerve Growth Factor
keywords: autonomic; cardiac ganglia; heart failure; nerve growth factor; nervous system
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