Myocyte loss in chronic heart failure.
This study examined whether or not there is progressive loss of individual myocytes in established heart failure, accounting for the progressive left ventricular dysfunction; whether such loss is by necrosis or apoptosis; and whether such loss is more pronounced in ischaemic heart disease or idiopathic dilated cardiomyopathy. Tissue for patients undergoing cardiac transplantation for clinical end-stage heart disease was used. The clinical diagnosis was not known to the observer at the time of analysis. Indices of potential myocyte loss were: detection of apoptotic nuclei in situ, using the TUNEL method, immunohistochemistry for CD120a, CD120b, CD95, perforin and granzyme B; binding of C9 complex; and lipofuscin deposition within macrophages. Interstitial macrophages and T cells and their relationship to myocyte loss were also examined. There is indeed low grade myocyte loss in chronic heart failure, but there was no difference between the disease groups; rather, there was marked patient-to-patient variation within each category. Thus in chronic heart failure myocyte loss does occur, and both necrosis and apoptosis contribute to this loss, irrespective of the underlying nature of the disease. Any mechanism which accounts for myocyte loss must be common to both conditions, rather than specific for a pre-operative diagnosis.
Rayment
N B
NB
Department of Immunology, UCL Medical School, Windeyer Building, 46 Cleveland Street, London W1P 6DB, U.K.
Haven
A J
AJ
Madden
B
B
Murday
A
A
Trickey
R
R
Shipley
M
M
Davies
M J
MJ
Katz
D R
DR
D000328:Adult; D000368:Aged; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000473:pathology; D002908:Chronic Disease; D005260:Female; D053804:Granzymes; D006333:Heart Failure / Q000209:etiology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D009336:Necrosis; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019014:fas Receptor / Q000032:analysis; D014841:von Willebrand Factor / Q000032:analysis
D015415:Biomarkers; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D014841:von Willebrand Factor; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases