PMID- 8149524
OWN - NLM
STAT- MEDLINE
DCOM- 19940509
LR  - 20190623
IS  - 0009-7322 (Print)
IS  - 0009-7322 (Linking)
VI  - 89
IP  - 4
DP  - 1994 Apr
TI  - Endothelin in human congestive heart failure.
PG  - 1580-6
AB  - BACKGROUND: Although recent investigations report the elevation of plasma 
      endothelin (ET) in congestive heart failure (CHF), it remains unclear if this 
      elevation is that of the biologically active peptide ET-1 or of its precursor 
      big-ET. Furthermore, it is unclear if such elevation is associated with increased 
      myocardial ET and if the molecular form from cardiac tissue is altered ET. Last, 
      it remains to be established whether circulating ET is increased at the earliest 
      stage of CHF in patients with asymptomatic left ventricular dysfunction and 
      correlates with the magnitude of ventricular dysfunction. METHODS AND RESULTS: 
      The present study was designed to investigate concentrations and molecular forms 
      of ET in plasma and cardiac tissue in healthy subjects and CHF patients with New 
      York Heart Association (NYHA) class I through IV using cardiac radionuclide 
      angiogram, cardiac myocardial biopsy, radioimmunoassay, gel permeation 
      chromatography (GPC), and immunohistochemical staining (IHCS). Plasma ET was 
      increased only in patients with moderate (NYHA class III) or severe (NYHA class 
      IV) CHF compared with healthy subjects and individuals with asymptomatic (NYHA 
      class I) or mild (NYHA class II) CHF. The elevation of circulating ET in CHF 
      showed a negative correlation with left ventricular ejection fraction and cardiac 
      index and a positive correlation with functional class and left ventricular 
      end-diastolic volume index. GPC demonstrated that immunoreactive plasma ET was 
      ET-1 in healthy subjects and both mature ET-1 and its precursor big-ET in severe 
      CHF patients, with big-ET the predominant molecular form. Cardiac tissue 
      concentrations and IHCS revealed ET presence in healthy atrial and ventricular 
      tissue, which were not different in severe CHF. GPC revealed that the molecular 
      form of cardiac ET was ET-1 in both healthy and CHF hearts. CONCLUSIONS: The 
      present study establishes for the first time that the elevation of plasma ET in 
      severe human CHF represents principally elevation of big-ET. Second, ET is 
      present in healthy and failing myocardia, and its activity by both 
      immunohistochemistry and radioimmunoassay is not changed in CHF. Furthermore, the 
      elevated plasma ET is characteristic of severe CHF and not asymptomatic or mild 
      CHF. In addition, the degree of plasma elevation of ET correlates with the 
      magnitude of alterations in cardiac hemodynamics and functional class. The 
      present study confirms and extends previous investigations of ET in human CHF and 
      establishes the evolution of circulating and local cardiac ET in the spectrum of 
      human CHF.
FAU - Wei, C M
AU  - Wei CM
AD  - Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, MN 55905.
FAU - Lerman, A
AU  - Lerman A
FAU - Rodeheffer, R J
AU  - Rodeheffer RJ
FAU - McGregor, C G
AU  - McGregor CG
FAU - Brandt, R R
AU  - Brandt RR
FAU - Wright, S
AU  - Wright S
FAU - Heublein, D M
AU  - Heublein DM
FAU - Kao, P C
AU  - Kao PC
FAU - Edwards, W D
AU  - Edwards WD
FAU - Burnett, J C Jr
AU  - Burnett JC Jr
LA  - eng
GR  - HL-07111/HL/NHLBI NIH HHS/United States
GR  - HL-36634/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Endothelin-1)
RN  - 0 (Endothelins)
RN  - 0 (Protein Precursors)
SB  - IM
MH  - Chromatography, Gel
MH  - Endothelin-1
MH  - Endothelins/*analysis/chemistry
MH  - Female
MH  - Heart Failure/blood/*metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Middle Aged
MH  - Myocardium/*chemistry
MH  - Protein Precursors/analysis/chemistry
MH  - Radioimmunoassay
MH  - Ventricular Function, Left/physiology
EDAT- 1994/04/01 00:00
MHDA- 2001/03/28 10:01
CRDT- 1994/04/01 00:00
PHST- 1994/04/01 00:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1994/04/01 00:00 [entrez]
AID - 10.1161/01.cir.89.4.1580 [doi]
PST - ppublish
SO  - Circulation. 1994 Apr;89(4):1580-6. doi: 10.1161/01.cir.89.4.1580.