PMID- 11729726
OWN - NLM
STAT- MEDLINE
DCOM- 20020215
LR  - 20131121
IS  - 0914-5087 (Print)
IS  - 0914-5087 (Linking)
VI  - 38
IP  - 5
DP  - 2001 Nov
TI  - [Effects of long-term treatment with prostacyclin on plasma adrenomedullin in 
      patients with primary pulmonary hypertension].
PG  - 263-71
AB  - OBJECTIVES: This study investigated whether plasma levels of adrenomedullin, a 
      potent vasodilating endogenous neurohumoral mediator, are useful for assessing 
      the severity of primary pulmonary hypertension. METHODS: Seventeen pediatric 
      patients with primary pulmonary hypertension (eight girls, nine boys, mean age 12 
      +/- 4 years) were enrolled in this study. Thirteen patients in New York Heart 
      Association (NYHA) classes III and IV had been treated with long-term continuous 
      intravenous prostacyclin (PGI2) infusion therapy, and four patients in classes I 
      and II had received beraprost sodium, an oral PGI2 analogue. Blood samples were 
      taken from all patients at the first visit. Plasma levels of atrial and brain 
      natriuretic peptide (ANP, BNP) and endothelin-1, and mature-type adrenomedullin 
      were measured. The relationships were investigated between neurohumoral mediator 
      levels and NYHA class, pulmonary hemodynamics, and exercise capacity assessed by 
      6-minute walk test. The changes in neurohumoral mediator levels at 1 month, 3 
      months, and 6 to 12 months were also evaluated in 11 survivors with long-term 
      PGI2 treatment. RESULTS: All neurohumoral mediator levels were positively 
      correlated with severity of NYHA class. Patients in class IV demonstrated 
      significantly elevated neurohumoral mediator levels, except endothelin-1, in 
      comparison with patients in classes I-III. Neurohumoral mediator levels had a 
      significant negative correlation with exercise capacity. Stepwise regression 
      analysis revealed that the BNP to ANP ratio (BNP/ANP) was the most powerful 
      independent factor for total pulmonary resistance (r = 0.85, p = 0.0071) and 
      cardiac index (r = 0.84, p = 0.009). Adrenomedullin was significantly correlated 
      with BNP (r = 0.53, p = 0.03), endothelin-1 (r = 0.66, p = 0.006), and BNP/ANP (r 
      = 0.73, p = 0.0009). ANP and BNP decreased from 196 +/- 213 and 494 +/- 361 pg/ml 
      at baseline to 74 +/- 47 and 153 +/- 133 pg/ml at 1 month, respectively. There 
      was an apparent re-increase in both ANP (187 +/- 194 pg/ml) and BNP (466 +/- 621 
      pg/ml) at 3 months, regardless of improvement in NYHA class and exercise capacity 
      after long-term PGI2 treatment. In contrast, adrenomedullin decreased from 3.0 
      +/- 2.2 (baseline) to 1.7 +/- 0.7 fmol/ml at 1 month and 1.6 +/- 0.5 fmol/ml at 3 
      months. Adrenomedullin was slightly increased at 6-12 months (2.1 +/- 0.9 
      fmol/ml) without statistical significance. There was a significant relationship 
      between the changes in adrenomedullin at 3 months compared to values at 
      initiation of PGI2 therapy and the changes in mean pulmonary arterial pressure (r 
      = 0.97, p = 0.0041). CONCLUSIONS: Plasma levels of neurohumoral mediators are 
      useful for assessing the severity of primary pulmonary hypertension. In 
      particular, adrenomedullin was valuable for evaluating both cardiac performance 
      and pulmonary hemodynamics after long-term treatment with PGI2 in patients with 
      primary pulmonary hypertension.
FAU - Nakayama, T
AU  - Nakayama T
AD  - First Department of Pediatrics, Toho University School of Medicine, Ohmorinishi 
      6-11-1, Ohta-ku, Tokyo 143-8541.
FAU - Ishikita, T
AU  - Ishikita T
FAU - Matsuura, H
AU  - Matsuura H
FAU - Saji, T
AU  - Saji T
LA  - jpn
PT  - English Abstract
PT  - Journal Article
PL  - Netherlands
TA  - J Cardiol
JT  - Journal of cardiology
JID - 8804703
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Endothelin-1)
RN  - 0 (Peptides)
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
RN  - 148498-78-6 (Adrenomedullin)
RN  - 35E3NJJ4O6 (beraprost)
RN  - 85637-73-6 (Atrial Natriuretic Factor)
RN  - DCR9Z582X0 (Epoprostenol)
SB  - IM
MH  - Adolescent
MH  - Adrenomedullin
MH  - Antihypertensive Agents/*administration & dosage/pharmacology
MH  - Atrial Natriuretic Factor/blood
MH  - Child
MH  - Child, Preschool
MH  - Endothelin-1
MH  - Epoprostenol/*administration & dosage/*analogs & derivatives/pharmacology
MH  - Exercise Tolerance/drug effects
MH  - Female
MH  - Hemodynamics/drug effects
MH  - Humans
MH  - Hypertension, Pulmonary/*blood/*drug therapy
MH  - Infusions, Intravenous
MH  - Male
MH  - Natriuretic Peptide, Brain/blood
MH  - Peptides/*blood
EDAT- 2001/12/04 10:00
MHDA- 2002/02/16 10:01
CRDT- 2001/12/04 10:00
PHST- 2001/12/04 10:00 [pubmed]
PHST- 2002/02/16 10:01 [medline]
PHST- 2001/12/04 10:00 [entrez]
PST - ppublish
SO  - J Cardiol. 2001 Nov;38(5):263-71.